Skin Angiosarcoma Clinical Trial
Official title:
A Multicenter Phase II Trial of Paclitaxel With and Without Nivolumab in Taxane Naive, and Nivolumab and Cabozantinib in Taxane Pretreated Subjects With Angiosarcoma
| Verified date | November 2023 |
| Source | National Cancer Institute (NCI) |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This phase II trial studies how well paclitaxel with and without nivolumab works in treating patients with soft tissue sarcoma that have not received taxane drugs, and how well nivolumab and cabozantinib work in treating taxane pretreated patients with soft tissue sarcoma. Nivolumab works through the body's immune system to help the immune system act against tumor cells. Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This trial is being done to see if the combination of nivolumab and paclitaxel or cabozantinib can shrink soft tissue sarcoma and possibly prevent it from coming back.
| Status | Active, not recruiting |
| Enrollment | 90 |
| Est. completion date | September 30, 2024 |
| Est. primary completion date | September 30, 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Histologically confirmed cutaneous or visceral angiosarcoma, where curative treatment is either not possible or curative modality therapy is declined by the subject. Note: If a subject declines curative modality therapy, the reason must be documented (e.g. excessive morbidity to necessary surgery) - Note: Radiation induced angiosarcomas are permitted - All local diagnostic slides AND 5 x 4-6 micron unstained slides from diagnostic tumor tissue should be available for retrospective central pathology review - Must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Per RECIST v1.1, clinical lesions will only be considered measurable when they are superficial and >= 10 mm diameter as assessed using calipers or ruler (e.g. skin nodules). For the case of skin lesions, documentation by color photography including a ruler to estimate the size of the lesion is required. When lesions can be evaluated by both clinical exam and imagining, imaging evaluation should be undertaken since it is more objective and may also be reviewed at the end of the study. The same method of measurement should be used throughout the study, preferably performed by the same investigator. Areas previously radiated must have demonstrated disease progression at some point over the past 6 months and growth must be subsequent to the last line of anti-cancer directed therapy (e.g. chemotherapy, radiation therapy, surgery) - Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown - Therefore, for women of childbearing potential only, a negative pregnancy test done =< 3 days prior to registration is required - Age >= 18 years - Eastern Cooperative Oncology Group (ECOG) performance status 0-1 - Prior Treatment - Patient must have completed all prior cancer directed therapies (including investigational) >= 7 days prior to cycle 1 day 1 - Exception: prostate patients who are allowed to concurrently receive androgen suppression therapy - Note: Radiation therapy must be completed >= 7 days of day 1 of study treatment, and must not be expected to significantly impact blood count recovery - There is no limit to overall number of prior lines of therapy - No prior PD-1 inhibitor or PD-L1 inhibitor therapy is permitted - No prior administration of VEGF TKI therapy is permitted - Recovery to baseline or' =< grade 1 CTCAE version 5.0 from toxicity related to any prior treatment, unless adverse events are clinically non-significant and/or stable on supportive therapy, with the exception of fatigue (which should be =< grade 2) or alopecia. Note: Patients should be expected to have experienced any nadir and have adequate blood count recovery prior to cycle 1 day 1 - Taxane Naive Patients Only: No prior exposure to taxane therapy of any duration for angiosarcoma - Taxane Pre-treated Patients Only (Effective 10/28/2021, new patient accrual to Arm 3 was permanently closed): Prior taxane therapy is allowed at any point prior to registration as long as prior treatment eligibility criteria are met prior to cycle 1 day 1 - No major surgery (except the diagnostic biopsy) =< 28 days of study registration. Procedures such as thoracentesis, paracentesis, percutaneous biopsy, Lasik eye surgery are not considered major surgery. Subjects with clinically relevant ongoing complications from prior surgery are not eligible - Absolute neutrophil count (ANC) >= 1,500/mm^3 - Platelet count >= 100,000/mm^3 - Hemoglobin >= 9.0 g/dL - Calculated (Calc.) creatinine clearance >= 30 mL/min (per Cockcroft-Gault) - Total bilirubin =< 1.5 x upper limit of normal (ULN) - For patients with documented/suspected Gilbert's disease, bilirubin =< 3 x ULN - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) - For patients with significant hepatic metastases, ALT and AST =< 5 x ULN. No clinically active or chronic liver disease resulting in moderate/severe hepatic impairment (Child-Pugh class B or C), ascites, coagulopathy or bleeding due to liver dysfunction - Urine protein:creatinine (UPC) ratio < 1 or urine protein =< 1+ (Only for Arm 3 Taxane pre-treated and crossover patients) - No uncontrolled central nervous system (CNS) metastases. Patients with history of CNS metastasis will be allowed as long as the metastatic sites were adequately treated as demonstrated by clinical and radiographic improvement, and the patient has recovered from the intervention (no residual adverse events > CTCAE grade 1), and the patient has remained without recurrence of new or worsening CNS symptoms for a period of 28 days prior to registration. Treated CNS metastasis (mets) should have no ongoing requirement for steroids, and no evidence of hemorrhage after treatment for at least 28 days prior to registration - No uncontrolled intercurrent illness that would put the patient at undue risk by participation in the study, in the opinion of the investigator - No history of syncope of cardiovascular etiology, uncontrolled cardiac arrhythmia, history of Mobitz II second degree or third degree heart block without a permanent pacemaker in place, myocardial ischemia or infarction, severe or unstable angina, New York Heart Association (NYHA) class II to IV heart failure, or stroke/transient ischemic attack (TIA) within the past 3 months - No thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 1 month before randomization. Subjects with a diagnosis of incidental, subsegmental pulmonary embolism (PE) or deep vein thrombosis (DVT) within 6 months are allowed if stable, asymptomatic, and treated with low molecular weight heparin (LMWH) for at least 2 weeks before first dose. Iatrogenic arterial embolization procedures such as tumor arterial embolization or splenic artery embolization are allowed - Patients with a requirement for steroid treatment or other immunosuppressive treatment: Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted - Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event) - Active autoimmune disease requiring systemic treatment (i.e. disease modifying agents, corticosteroids, or immunosuppressive drugs) within the past 2 years. These include but are not limited to patients with a history of immune-related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), rheumatoid arthritis, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease - Note: Patients are permitted to enroll if they have vitiligo; type I diabetes mellitus; hypothyroidism, pituitary or adrenal insufficiency requiring only hormone replacement; psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event) - Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial - No planned palliative procedures for alleviation of pain such as radiation therapy or surgery - No untreated or impending spinal cord compression or evidence of spinal metastases with a risk of impending fracture or spinal cord compression - No known or suspected contraindications or hypersensitivity to paclitaxel, cabozantinib or nivolumab or to any of the excipients - Disorders associated with a high risk of perforation or fistula formation: active inflammatory bowel disease, active diverticulitis, active cholecystitis, active symptomatic cholangitis or active appendicitis, active acute pancreatitis or active acute obstruction of the pancreatic or biliary duct, or active gastric outlet obstruction; abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before randomization. Note: Complete healing of an intra-abdominal abscess must be confirmed before randomization - No clinically significant hematuria, hematemesis, or hemoptysis, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 3 months before randomization - No lesions invading major pulmonary blood vessels - No other clinically significant disorders: uncompensated/symptomatic hypothyroidism; requirements for hemodialysis or peritoneal dialysis; history of solid organ transplantation - Serious non-healing wounds unrelated to cancer are excluded - Note: Wounds that are cutaneous angiosarcoma are allowed - Chronic concomitant treatment with strong inhibitors and inducers of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors and inducers must discontinue the drug 7 days and 14 days, respectively prior to registration on the study - Taxane Naive Patients Only: No clinically significant neuropathy (grade >= 2 per NCI CTCAE v5.0) - Taxane Pre-treated only (Effective 10/28/2021, new patient accrual to Arm 3 was permanently closed): - Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose. Subjects with a diagnosis of DVT within 6 months are allowed if stable and treated with LMWH for at least 2 weeks before first dose - No history of clinically significant coagulopathy - No uncontrolled hypertension, defined as systolic blood pressure of > 140 mmHg or diastolic pressure > 90 mmHg on anti-hypertensive medications - No known or suspected gastrointestinal disorder affecting absorption of oral medications (for patients getting cabozantinib) - No clinical, laboratory or radiographic evidence of an active bacterial, fungal, or viral infection requiring treatment at the time of registration. No concurrent use of parenteral (IV) antibiotics is permitted. Oral antibiotics administered for a defined course with expectation of resolution of infection are permitted at the discretion of the investigator - No use of ongoing systemic steroid therapy within 7 days prior to study registration. Dose equivalence of prednisone 10mg daily or less is permitted - Taxane Pre-treated only: - No current use of aspirin (> 81 mg/day), or any other antiplatelet agents - Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin inhibitors, and factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel) is not permitted. Low-dose (prophylactic) low molecular weight heparins (LMWH) are permitted. Anticoagulation with therapeutic doses of LMWH is allowed in subjects with no known brain metastases, no clinically significant hemorrhage, or no complications from a thromboembolic event on the anticoagulation regimen, and who have been on a stable dose of LMWH for at least 2 weeks before first dose - Patients must be able to speak and comprehend English or Spanish in order to complete the mandatory patient-completed measures - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown - Therefore, for women of childbearing potential only, a negative pregnancy test done =< 3 days prior to re-registration is required - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Age >= 18 years - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): ECOG performance status 0-1 - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Prior Treatment - Patient must have completed all prior treatments (including investigational Arm 2 paclitaxel) >= 28 days prior to cycle 1 day 1 - Exception: prostate patients who are allowed to concurrently receive androgen suppression therapy - Note: Re-registration is only permitted after progression on Arm 2 - No prior PD-1 inhibitor or PD-L1 inhibitor therapy is permitted - Recovery to baseline, or =< grade 1 CTCAE version 5.0 from toxicity related to any prior treatment, unless adverse events are clinically non-significant and/or stable on supportive therapy, with the exception of fatigue (which should be =< grade 2) or alopecia. Note: Patients should be expected to have experienced any nadir and have adequate blood count recovery prior to cycle 1 day 1 - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): No major surgery (except the diagnostic biopsy) =< 28 days of study re-registration. Procedures such as thoracentesis, paracentesis, percutaneous biopsy, Lasik eye surgery are not considered major surgery. Subjects with clinically relevant ongoing complications from prior surgery are not eligible - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Absolute neutrophil count (ANC) >= 1,500/mm^3 - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Platelet count >= 100,000/mm^3 - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Hemoglobin >= 9.0 g/dL - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Calc. creatinine clearance >= 30 mL/min (per Cockcroft-Gault) - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Total bilirubin =< 1.5 x upper limit of normal (ULN) - For patients with documented/suspected Gilbert's disease, bilirubin =< 3 x ULN - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): AST/ALT =< 2.5 x upper limit of normal (ULN) - For patients with significant hepatic metastases, ALT and AST =< 5 x ULN. No clinically active or chronic liver disease resulting in moderate/severe hepatic impairment (Child-Pugh class B or C), ascites, coagulopathy or bleeding due to liver dysfunction - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): UPC ratio < 1 or urine protein =< 1+ - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): No uncontrolled CNS metastases. Patients with history of CNS metastasis will be allowed as long as the metastatic sites were adequately treated as demonstrated by clinical and radiographic improvement, and the patient has recovered from the intervention (no residual adverse events > CTCAE grade 1), and the patient has remained without recurrence of new or worsening CNS symptoms for a period of 28 days prior to registration. Treated CNS mets should have no ongoing requirement for steroids, and no evidence of hemorrhage after treatment for at least 28 days prior to registration - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): No uncontrolled intercurrent illness that would put the patient at undue risk by participation in the study, in the opinion of the investigator - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): No history of syncope of cardiovascular etiology, uncontrolled cardiac arrhythmia, History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place, myocardial ischemia or infarction, severe or unstable angina, New York Heart Association (NYHA) class II to IV heart failure, or stroke/transient ischemic attack (TIA) within the past 3 months - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): No thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 1 month before randomization. Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with LMWH for at least 2 weeks before first dose. Iatrogenic arterial embolization procedures such as tumor arterial embolization or splenic artery embolization are allowed - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Patients with a requirement for steroid treatment or other immunosuppressive treatment: Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Active autoimmune disease requiring systemic treatment (i.e. disease modifying agents, corticosteroids, or immunosuppressive drugs) within the past 2 years. These include but are not limited to patients with a history of immune-related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as SLE, rheumatoid arthritis, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease - Note: Patients are permitted to enroll if they have vitiligo; type I diabetes mellitus; hypothyroidism, pituitary or adrenal insufficiency requiring only hormone replacement; psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event) - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): No planned palliative procedures for alleviation of pain such as radiation therapy or surgery - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): No untreated or impending spinal cord compression or evidence of spinal metastases with a risk of impending fracture or spinal cord compression - Re-Registration Eligibility Criteria (upon progression on Arm 2 only): No known or suspected contraindications or hypersensitivity to cabozantinib or nivolumab or to any of the exc |
| Country | Name | City | State |
|---|---|---|---|
| Guam | FHP Health Center-Guam | Tamuning | |
| United States | Hawaii Cancer Care - Westridge | 'Aiea | Hawaii |
| United States | Pali Momi Medical Center | 'Aiea | Hawaii |
| United States | Queen's Cancer Center - Pearlridge | 'Aiea | Hawaii |
| United States | The Cancer Center of Hawaii-Pali Momi | 'Aiea | Hawaii |
| United States | The Queen's Medical Center - West Oahu | 'Ewa Beach | Hawaii |
| United States | Saint Anthony's Health | Alton | Illinois |
| United States | Mary Greeley Medical Center | Ames | Iowa |
| United States | McFarland Clinic - Ames | Ames | Iowa |
| United States | University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan |
| United States | Emory University Hospital Midtown | Atlanta | Georgia |
| United States | Rush - Copley Medical Center | Aurora | Illinois |
| United States | UCHealth University of Colorado Hospital | Aurora | Colorado |
| United States | Saint Louis Cancer and Breast Institute-Ballwin | Ballwin | Missouri |
| United States | Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland |
| United States | Central Care Cancer Center - Bolivar | Bolivar | Missouri |
| United States | McFarland Clinic - Boone | Boone | Iowa |
| United States | Dana-Farber Cancer Institute | Boston | Massachusetts |
| United States | Massachusetts General Hospital Cancer Center | Boston | Massachusetts |
| United States | Roswell Park Cancer Institute | Buffalo | New York |
| United States | Fairview Ridges Hospital | Burnsville | Minnesota |
| United States | Minnesota Oncology - Burnsville | Burnsville | Minnesota |
| United States | Cambridge Medical Center | Cambridge | Minnesota |
| United States | UNC Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina |
| United States | Atrium Health Pineville/LCI-Pineville | Charlotte | North Carolina |
| United States | Carolinas Medical Center/Levine Cancer Institute | Charlotte | North Carolina |
| United States | Northwestern University | Chicago | Illinois |
| United States | Rush University Medical Center | Chicago | Illinois |
| United States | University of Chicago Comprehensive Cancer Center | Chicago | Illinois |
| United States | Ohio State University Comprehensive Cancer Center | Columbus | Ohio |
| United States | Mercy Hospital | Coon Rapids | Minnesota |
| United States | Siteman Cancer Center at West County Hospital | Creve Coeur | Missouri |
| United States | Carle at The Riverfront | Danville | Illinois |
| United States | Northwestern Medicine Cancer Center Kishwaukee | DeKalb | Illinois |
| United States | Smilow Cancer Hospital-Derby Care Center | Derby | Connecticut |
| United States | City of Hope Comprehensive Cancer Center | Duarte | California |
| United States | Duke University Medical Center | Durham | North Carolina |
| United States | Marshfield Medical Center-EC Cancer Center | Eau Claire | Wisconsin |
| United States | Fairview Southdale Hospital | Edina | Minnesota |
| United States | Carle Physician Group-Effingham | Effingham | Illinois |
| United States | NorthShore University HealthSystem-Evanston Hospital | Evanston | Illinois |
| United States | Smilow Cancer Hospital Care Center-Fairfield | Fairfield | Connecticut |
| United States | McFarland Clinic - Trinity Cancer Center | Fort Dodge | Iowa |
| United States | Mercy Hospital Fort Smith | Fort Smith | Arkansas |
| United States | Parkview Regional Medical Center | Fort Wayne | Indiana |
| United States | Vanderbilt-Ingram Cancer Center Cool Springs | Franklin | Tennessee |
| United States | Unity Hospital | Fridley | Minnesota |
| United States | Gibbs Cancer Center-Gaffney | Gaffney | South Carolina |
| United States | University of Florida Health Science Center - Gainesville | Gainesville | Florida |
| United States | Central Care Cancer Center - Garden City | Garden City | Kansas |
| United States | Northwestern Medicine Cancer Center Delnor | Geneva | Illinois |
| United States | Smilow Cancer Hospital Care Center at Glastonbury | Glastonbury | Connecticut |
| United States | NorthShore University HealthSystem-Glenbrook Hospital | Glenview | Illinois |
| United States | Central Care Cancer Center - Great Bend | Great Bend | Kansas |
| United States | Smilow Cancer Hospital Care Center at Greenwich | Greenwich | Connecticut |
| United States | Gibbs Cancer Center-Pelham | Greer | South Carolina |
| United States | Smilow Cancer Hospital Care Center - Guilford | Guilford | Connecticut |
| United States | Hackensack University Medical Center | Hackensack | New Jersey |
| United States | Smilow Cancer Hospital Care Center at Saint Francis | Hartford | Connecticut |
| United States | NorthShore University HealthSystem-Highland Park Hospital | Highland Park | Illinois |
| United States | Hawaii Cancer Care Inc - Waterfront Plaza | Honolulu | Hawaii |
| United States | Hawaii Cancer Care Inc-Liliha | Honolulu | Hawaii |
| United States | Hawaii Diagnostic Radiology Services LLC | Honolulu | Hawaii |
| United States | Island Urology | Honolulu | Hawaii |
| United States | Kapiolani Medical Center for Women and Children | Honolulu | Hawaii |
| United States | Kuakini Medical Center | Honolulu | Hawaii |
| United States | Queen's Cancer Cenrer - POB I | Honolulu | Hawaii |
| United States | Queen's Cancer Center - Kuakini | Honolulu | Hawaii |
| United States | Queen's Medical Center | Honolulu | Hawaii |
| United States | Straub Clinic and Hospital | Honolulu | Hawaii |
| United States | The Cancer Center of Hawaii-Liliha | Honolulu | Hawaii |
| United States | University of Hawaii Cancer Center | Honolulu | Hawaii |
| United States | Mayo Clinic in Florida | Jacksonville | Florida |
| United States | McFarland Clinic - Jefferson | Jefferson | Iowa |
| United States | Freeman Health System | Joplin | Missouri |
| United States | Mercy Hospital Joplin | Joplin | Missouri |
| United States | Straub Medical Center - Kahului Clinic | Kahului | Hawaii |
| United States | Castle Medical Center | Kailua | Hawaii |
| United States | Northwestern Medicine Lake Forest Hospital | Lake Forest | Illinois |
| United States | Northwell Health/Center for Advanced Medicine | Lake Success | New York |
| United States | Cancer Centers of Southwest Oklahoma Research | Lawton | Oklahoma |
| United States | Wilcox Memorial Hospital and Kauai Medical Clinic | Lihue | Hawaii |
| United States | Fairview Clinics and Surgery Center Maple Grove | Maple Grove | Minnesota |
| United States | Minnesota Oncology Hematology PA-Maplewood | Maplewood | Minnesota |
| United States | Saint John's Hospital - Healtheast | Maplewood | Minnesota |
| United States | McFarland Clinic - Marshalltown | Marshalltown | Iowa |
| United States | Marshfield Medical Center-Marshfield | Marshfield | Wisconsin |
| United States | Carle Physician Group-Mattoon/Charleston | Mattoon | Illinois |
| United States | Medical College of Wisconsin | Milwaukee | Wisconsin |
| United States | Abbott-Northwestern Hospital | Minneapolis | Minnesota |
| United States | Health Partners Inc | Minneapolis | Minnesota |
| United States | Hennepin County Medical Center | Minneapolis | Minnesota |
| United States | Marshfield Clinic-Minocqua Center | Minocqua | Wisconsin |
| United States | UPMC Hillman Cancer Center - Monroeville | Monroeville | Pennsylvania |
| United States | Monticello Cancer Center | Monticello | Minnesota |
| United States | Good Samaritan Regional Health Center | Mount Vernon | Illinois |
| United States | Vanderbilt Breast Center at One Hundred Oaks | Nashville | Tennessee |
| United States | Vanderbilt University/Ingram Cancer Center | Nashville | Tennessee |
| United States | Yale University | New Haven | Connecticut |
| United States | Cancer Center of Western Wisconsin | New Richmond | Wisconsin |
| United States | New Ulm Medical Center | New Ulm | Minnesota |
| United States | Memorial Sloan Kettering Cancer Center | New York | New York |
| United States | NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center | New York | New York |
| United States | Yale-New Haven Hospital North Haven Medical Center | North Haven | Connecticut |
| United States | Mercy Hospital Oklahoma City | Oklahoma City | Oklahoma |
| United States | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma |
| United States | Nebraska Methodist Hospital | Omaha | Nebraska |
| United States | Smilow Cancer Hospital-Orange Care Center | Orange | Connecticut |
| United States | Fox Chase Cancer Center | Philadelphia | Pennsylvania |
| United States | Thomas Jefferson University Hospital | Philadelphia | Pennsylvania |
| United States | Mayo Clinic Hospital in Arizona | Phoenix | Arizona |
| United States | University of Pittsburgh Cancer Institute (UPCI) | Pittsburgh | Pennsylvania |
| United States | UPMC-Saint Margaret | Pittsburgh | Pennsylvania |
| United States | Oregon Health and Science University | Portland | Oregon |
| United States | Fairview Northland Medical Center | Princeton | Minnesota |
| United States | Marshfield Medical Center-Rice Lake | Rice Lake | Wisconsin |
| United States | Virginia Commonwealth University/Massey Cancer Center | Richmond | Virginia |
| United States | North Memorial Medical Health Center | Robbinsdale | Minnesota |
| United States | Mayo Clinic in Rochester | Rochester | Minnesota |
| United States | Delbert Day Cancer Institute at PCRMC | Rolla | Missouri |
| United States | Mercy Clinic-Rolla-Cancer and Hematology | Rolla | Missouri |
| United States | Heartland Regional Medical Center | Saint Joseph | Missouri |
| United States | Mercy Hospital Saint Louis | Saint Louis | Missouri |
| United States | Mercy Hospital South | Saint Louis | Missouri |
| United States | Saint Louis Cancer and Breast Institute-South City | Saint Louis | Missouri |
| United States | Siteman Cancer Center at Christian Hospital | Saint Louis | Missouri |
| United States | Siteman Cancer Center-South County | Saint Louis | Missouri |
| United States | Washington University School of Medicine | Saint Louis | Missouri |
| United States | Park Nicollet Clinic - Saint Louis Park | Saint Louis Park | Minnesota |
| United States | Regions Hospital | Saint Paul | Minnesota |
| United States | United Hospital | Saint Paul | Minnesota |
| United States | Siteman Cancer Center at Saint Peters Hospital | Saint Peters | Missouri |
| United States | Huntsman Cancer Institute/University of Utah | Salt Lake City | Utah |
| United States | University of Utah Sugarhouse Health Center | Salt Lake City | Utah |
| United States | Mayo Clinic in Arizona | Scottsdale | Arizona |
| United States | FHCC South Lake Union | Seattle | Washington |
| United States | Fred Hutchinson Cancer Research Center | Seattle | Washington |
| United States | University of Washington Medical Center - Montlake | Seattle | Washington |
| United States | Saint Francis Regional Medical Center | Shakopee | Minnesota |
| United States | LSU Health Sciences Center at Shreveport | Shreveport | Louisiana |
| United States | North Grove Medical Park | Spartanburg | South Carolina |
| United States | Spartanburg Medical Center | Spartanburg | South Carolina |
| United States | Spartanburg Medical Center - Mary Black Campus | Spartanburg | South Carolina |
| United States | CoxHealth South Hospital | Springfield | Missouri |
| United States | Mercy Hospital Springfield | Springfield | Missouri |
| United States | Marshfield Medical Center-River Region at Stevens Point | Stevens Point | Wisconsin |
| United States | Lakeview Hospital | Stillwater | Minnesota |
| United States | Moffitt Cancer Center | Tampa | Florida |
| United States | Moffitt Cancer Center - McKinley Campus | Tampa | Florida |
| United States | Moffitt Cancer Center-International Plaza | Tampa | Florida |
| United States | Smilow Cancer Hospital-Torrington Care Center | Torrington | Connecticut |
| United States | Smilow Cancer Hospital Care Center-Trumbull | Trumbull | Connecticut |
| United States | Banner University Medical Center - Tucson | Tucson | Arizona |
| United States | University of Arizona Cancer Center-North Campus | Tucson | Arizona |
| United States | University of Arizona Cancer Center-Orange Grove Campus | Tucson | Arizona |
| United States | MGC Hematology Oncology-Union | Union | South Carolina |
| United States | Carle Cancer Center | Urbana | Illinois |
| United States | The Carle Foundation Hospital | Urbana | Illinois |
| United States | Ridgeview Medical Center | Waconia | Minnesota |
| United States | Northwestern Medicine Cancer Center Warrenville | Warrenville | Illinois |
| United States | Mercy Hospital Washington | Washington | Missouri |
| United States | Sibley Memorial Hospital | Washington | District of Columbia |
| United States | Smilow Cancer Hospital-Waterbury Care Center | Waterbury | Connecticut |
| United States | Smilow Cancer Hospital Care Center - Waterford | Waterford | Connecticut |
| United States | Smilow Cancer Hospital Care Center - Westerly | Westerly | Rhode Island |
| United States | Marshfield Medical Center - Weston | Weston | Wisconsin |
| United States | Divine Providence Hospital | Williamsport | Pennsylvania |
| United States | UPMC Susquehanna | Williamsport | Pennsylvania |
| United States | Rice Memorial Hospital | Willmar | Minnesota |
| United States | Minnesota Oncology Hematology PA-Woodbury | Woodbury | Minnesota |
| United States | Fairview Lakes Medical Center | Wyoming | Minnesota |
| United States | Rush-Copley Healthcare Center | Yorkville | Illinois |
| Lead Sponsor | Collaborator |
|---|---|
| National Cancer Institute (NCI) |
United States, Guam,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Progression free survival (PFS) in taxane naive patients with angiosarcoma | Will compare the PFS in taxane naive angiosarcoma patients receiving either (1) paclitaxel + nivolumab compared to (2) paclitaxel alone. | From registration (randomization) to either progression or death (without progression), assessed up to 3 years | |
| Primary | Overall response rate (ORR) in angiosarcoma patients who have had prior taxane | Will compare the overall response rate (ORR) of nivolumab + cabozantinib in patients with angiosarcoma who have had prior taxanes to historical control of VEGF inhibitors alone. | Up to 3 years | |
| Secondary | ORR in the nivolumab + paclitaxel | Will be estimated by dividing the number of evaluable patients that achieve a confirmed response by the total number of evaluable patients in the nivolumab + paclitaxel combination arm. Additionally a 95% confidence interval will be constructed utilizing properties of the binomial distribution. | Up to 3 years | |
| Secondary | Overall survival in each of the 2 combination arms | Will be evaluated using the Kaplan-Meier method in order to determine the median survival rate. This median survival rate will be calculated for each of the 2 combination arms (i.e. nivolumab + paclitaxel and nivolumab + cabozantinib). | From study enrollment until death due to any cause, assessed up to 3 years | |
| Secondary | PFS rate | At 6 months | ||
| Secondary | Incidence of adverse events | Maximum grade adverse events will be summarized by treatment arm in a tabular setting. This will be done both with and without regard to the assigned attribution of each adverse event. | Up to 3 years | |
| Secondary | Patient-reported outcomes (PRO) | Will be assessed via PRO-Common Terminology Criteria for Adverse Events (CTCAE). In order to evaluate this endpoint we will calculate the proportion of patients that report a grade 3+ event along with a 95% confidence interval based on the properties of the binomial distribution. Any other analyses with these data will be done in an exploratory and hypothesis generating manner. | Up to 3 years |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Terminated |
NCT05729425 -
Evaluating the Accuracy of Microvessel Ultrasound Imaging for Detecting Extent of Disease in Patients With Angiosarcoma of the Skin
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