Mucosal Melanoma Clinical Trial
Official title:
A Randomized Phase II Trial of Adjuvant Nivolumab With or Without Cabozantinib in Patients With Resected Mucosal Melanoma
Verified date | March 2024 |
Source | National Cancer Institute (NCI) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This phase II trial tests whether nivolumab in combination with cabozantinib works in patients with mucosal melanoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps stop the spread of tumor cells. Giving nivolumab in combination with cabozantinib could prevent cancer from returning.
Status | Recruiting |
Enrollment | 99 |
Est. completion date | December 19, 2024 |
Est. primary completion date | December 19, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - STEP 0 INCLUSION CRITERIA - Histologically proven mucosal melanoma by local pathology - Central PD-L1 tumor tissue submission - STEP 1 INCLUSION CRITERIA - Receipt of the central PD-L1 testing results available - Disease status-Resected R0 or R1 disease patients. Patients eligible for randomization have resected R0 or R1 disease (with negative margins or positive microscopic margins) that must meet one of the following 4 criteria as defined below: - Regional lymph node (LN) involvement; OR - In-transit metastases/satellite primary disease; OR - Single localized, primary disease meeting one of the following site-specific requirements: - Head/neck - Sinonasal (including nasopharynx): any primary lesion; Nasal or oral cavity; pT4a or above, given slightly improved OS - NOTE: Conjunctival: does not meet the qualification for eligibility - Anorectal - any primary lesion - Vaginal/cervical - any primary, as they have 5 year OS rates of 5-25 - Urinary tract - any primary urethral or bladder tumor - Penile - Vulvar- AJCC cutaneous stage IIB or higher - Esophageal/gallbladder - any primary - Locoregionally recurrent following prior resection, meeting at least one of the above criteria - In addition, patients must have undergone cross-sectional imaging of the brain, chest, abdomen and pelvis with no evidence of distant metastatic disease - Disease status-Non-resected R2 or metastatic disease patients - Non-resected R2 or metastatic disease that is assessable and measurable radiographically or by physical examination - Prior Treatment: - No prior systemic checkpoint inhibitor therapy of mucosal melanoma, including in the adjuvant setting, is allowed. Prior adjuvant chemotherapy or interferon is allowed. - No other active, concurrent malignancy that requires ongoing systemic treatment or interferes with radiographic assessment of melanoma response as determined by the investigator. Exceptions may allow for adjuvant no evidence of disease (NED) cancers undergoing hormone based therapy may be eligible pending the other eligibility criteria are met and the principal investigator (PI) affirms the hormonal agent would not change the melanoma response. - Any radiation must have completed 28 days prior to randomization and the patient must have adequately recovered from its effects. - For resectable patients only: Surgery must have completed 28 days prior to randomization. - For resectable patients only: Surgery must have completed no more than 84 days prior to randomization. - Not pregnant and not nursing, because this study has an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required - Age >= 18 years - Eastern Cooperative Oncology Group (ECOG) performance status 0-2 - Absolute neutrophil count (ANC) >= 1,500/mm^3 - Platelet count >= 100,000/mm^3 - Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) >= 50mL/min/1.73 m^2 for patients with creatinine levels above institutional normal - Albumin >= 2.8 g/dL - Total bilirubin =< 1.5 x upper limit of normal (ULN) - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) - No cardiovascular disease, including: - No history of acute coronary syndromes (including myocardial infarction and unstable angina), coronary artery bypass graft (CABG) coronary angioplasty, or stenting within 6 months prior to study entry. - No history of current class II or higher congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system. - No refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg despite adequate attempts at anti-hypertensive therapy. - No history of myocarditis. - 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 Association (NYHA) class II to IV heart failure, or stroke/transient ischemic attack (TIA) within the past 3 months. - No corrected QT interval by Fridericia's formula (QTcF) > 500 msec. Note: if initial QTcF is found to be > 500 ms, two additional EKGs separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regard. - No underlying hematologic issues, including: - Congenital bleeding diathesis - Gastrointestinal (GI) bleeding requiring intervention within the past 6 months, unless directly related to mucosal melanoma - Active hemoptysis within 42 days prior to study enrollment. - Active tumor lesions with cavitations or tumor lesions which invade, encase, or abut major blood vessels. The anatomic location and characteristics of primary tumors or metastases as well as the medical history should be carefully reviewed in the selection of subjects for treatment with cabozantinib/placebo. - Pulmonary emboli or deep vein thromboses (DVT) that require an active anticoagulation regimen. - No known or suspected history of cytopenia (low white blood cell [WBC], hemoglobin or platelet count) of greater than 3 months duration with an unknown cause, myelodysplastic syndrome, or hematologic malignancies. - No clinical, laboratory or radiographic evidence of an active bacterial, fungal, or viral infection requiring treatment at the time of pre-registration (e.g., active symptoms of COVID-19 infection or a post-infectious symptomatic autoimmune syndrome, serious bacterial infections requiring antibiotics). - No known or suspected gastrointestinal disorder affecting absorption of oral medications. - Comorbid conditions: - No active autoimmune disease or any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of 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. - No history of autoimmune motor neuropathy (e.g., Guillain-Barre syndrome, myasthenia gravis) or non-infectious pneumonitis. - No history of severe allergic reactions to an unknown allergen or any components of the study drugs or its excipients. - No history of gastrointestinal perforation or abdominal fistula. - No clinically suspected central nervous system (CNS) (leptomeningeal or parenchymal) metastases. Patients with a history of CNS metastasis(s) will be allowed as long as - The metastatic site(s) were adequately treated as demonstrated by clinical and radiographic improvement, AND - The patient has recovered from the intervention (no residual adverse events > Common Terminology Criteria for Adverse Events [CTCAE] grade 1), AND - The patient has remained without occurrence of new or worsening CNS symptoms for a period of 28 days prior to enrollment. - No history of seizure or any condition that may increase the patient's seizure risk (e.g., prior cortical stroke, significant brain trauma) within 2 years. - 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. - No untreated spinal cord compression or evidence of spinal metastases with a risk of impending fracture or spinal cord compression. Spinal metastases must have completed planned radiation or surgical therapy prior to registration. - Concomitant medications: - Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 5 days prior to the start of study treatment. - Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 5 days prior to the start of study treatment. |
Country | Name | City | State |
---|---|---|---|
Canada | Jewish General Hospital | Montreal | Quebec |
Canada | Odette Cancer Centre- Sunnybrook Health Sciences Centre | Toronto | Ontario |
Canada | University Health Network-Princess Margaret Hospital | Toronto | Ontario |
United States | Mary Greeley Medical Center | Ames | Iowa |
United States | McFarland Clinic - Ames | Ames | Iowa |
United States | Community Hospital of Anaconda | Anaconda | Montana |
United States | Sutter Auburn Faith Hospital | Auburn | California |
United States | Rush - Copley Medical Center | Aurora | Illinois |
United States | UM Sylvester Comprehensive Cancer Center at Aventura | Aventura | Florida |
United States | Memorial Sloan Kettering Basking Ridge | Basking Ridge | New Jersey |
United States | Bronson Battle Creek | Battle Creek | Michigan |
United States | Alta Bates Summit Medical Center-Herrick Campus | Berkeley | California |
United States | Billings Clinic Cancer Center | Billings | Montana |
United States | Saint Alphonsus Cancer Care Center-Boise | Boise | Idaho |
United States | McFarland Clinic - Boone | Boone | Iowa |
United States | Dana-Farber Cancer Institute | Boston | Massachusetts |
United States | Bozeman Health Deaconess Hospital | Bozeman | Montana |
United States | Minnesota Oncology - Burnsville | Burnsville | Minnesota |
United States | Saint Alphonsus Cancer Care Center-Caldwell | Caldwell | Idaho |
United States | Miami Valley Hospital South | Centerville | Ohio |
United States | Centralia Oncology Clinic | Centralia | Illinois |
United States | Northwestern University | Chicago | Illinois |
United States | Case Western Reserve University | Cleveland | Ohio |
United States | Kootenai Health - Coeur d'Alene | Coeur d'Alene | Idaho |
United States | Mercy Hospital | Coon Rapids | Minnesota |
United States | UM Sylvester Comprehensive Cancer Center at Coral Gables | Coral Gables | Florida |
United States | Carle at The Riverfront | Danville | Illinois |
United States | Dayton Physician LLC - Englewood | Dayton | Ohio |
United States | Miami Valley Hospital | Dayton | Ohio |
United States | Miami Valley Hospital North | Dayton | Ohio |
United States | Premier Blood and Cancer Center | Dayton | Ohio |
United States | Cancer Care Specialists of Illinois - Decatur | Decatur | Illinois |
United States | Decatur Memorial Hospital | Decatur | Illinois |
United States | UM Sylvester Comprehensive Cancer Center at Deerfield Beach | Deerfield Beach | Florida |
United States | HSHS Sacred Heart Hospital | Eau Claire | Wisconsin |
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 | Crossroads Cancer Center | Effingham | Illinois |
United States | Parkland Health Center - Farmington | Farmington | Missouri |
United States | McFarland Clinic - Trinity Cancer Center | Fort Dodge | Iowa |
United States | Atrium Medical Center-Middletown Regional Hospital | Franklin | Ohio |
United States | Palo Alto Medical Foundation-Fremont | Fremont | California |
United States | Corewell Health Grand Rapids Hospitals - Butterworth Hospital | Grand Rapids | Michigan |
United States | Trinity Health Grand Rapids Hospital | Grand Rapids | Michigan |
United States | Benefis Sletten Cancer Institute | Great Falls | Montana |
United States | Saint Vincent Hospital Cancer Center at Saint Mary's | Green Bay | Wisconsin |
United States | Saint Vincent Hospital Cancer Center Green Bay | Green Bay | Wisconsin |
United States | Miami Valley Cancer Care and Infusion | Greenville | Ohio |
United States | Memorial Sloan Kettering Westchester | Harrison | New York |
United States | M D Anderson Cancer Center | Houston | Texas |
United States | McFarland Clinic - Jefferson | Jefferson | Iowa |
United States | Ascension Borgess Cancer Center | Kalamazoo | Michigan |
United States | Bronson Methodist Hospital | Kalamazoo | Michigan |
United States | West Michigan Cancer Center | Kalamazoo | Michigan |
United States | Kalispell Regional Medical Center | Kalispell | Montana |
United States | Kettering Medical Center | Kettering | Ohio |
United States | Cancer Centers of Southwest Oklahoma Research | Lawton | Oklahoma |
United States | Keck Medicine of USC Koreatown | Los Angeles | California |
United States | Los Angeles General Medical Center | Los Angeles | California |
United States | USC / Norris Comprehensive Cancer Center | Los Angeles | California |
United States | University of Wisconsin Carbone Cancer Center - University Hospital | Madison | Wisconsin |
United States | McFarland Clinic - Marshalltown | Marshalltown | Iowa |
United States | Carle Physician Group-Mattoon/Charleston | Mattoon | Illinois |
United States | University of Miami Miller School of Medicine-Sylvester Cancer Center | Miami | Florida |
United States | NYU Langone Hospital - Long Island | Mineola | New York |
United States | Abbott-Northwestern Hospital | Minneapolis | Minnesota |
United States | Marshfield Clinic-Minocqua Center | Minocqua | Wisconsin |
United States | Community Medical Center | Missoula | Montana |
United States | Memorial Medical Center | Modesto | California |
United States | Trinity Health Muskegon Hospital | Muskegon | Michigan |
United States | Saint Alphonsus Cancer Care Center-Nampa | Nampa | Idaho |
United States | Laura and Isaac Perlmutter Cancer Center at NYU Langone | New York | New York |
United States | Memorial Sloan Kettering Cancer Center | New York | New York |
United States | USC Norris Oncology/Hematology-Newport Beach | Newport Beach | California |
United States | Cancer and Hematology Centers of Western Michigan - Norton Shores | Norton Shores | Michigan |
United States | Cancer Care Center of O'Fallon | O'Fallon | Illinois |
United States | Saint Vincent Hospital Cancer Center at Oconto Falls | Oconto Falls | Wisconsin |
United States | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma |
United States | Saint Alphonsus Cancer Care Center-Ontario | Ontario | Oregon |
United States | Palo Alto Medical Foundation Health Care | Palo Alto | California |
United States | Stanford Cancer Institute Palo Alto | Palo Alto | California |
United States | Thomas Jefferson University Hospital | Philadelphia | Pennsylvania |
United States | University of Pittsburgh Cancer Institute (UPCI) | Pittsburgh | Pennsylvania |
United States | UM Sylvester Comprehensive Cancer Center at Plantation | Plantation | Florida |
United States | Kootenai Clinic Cancer Services - Post Falls | Post Falls | Idaho |
United States | Corewell Health Reed City Hospital | Reed City | Michigan |
United States | VCU Massey Cancer Center at Stony Point | Richmond | Virginia |
United States | Virginia Commonwealth University/Massey Cancer Center | Richmond | Virginia |
United States | Mayo Clinic in Rochester | Rochester | Minnesota |
United States | Sutter Roseville Medical Center | Roseville | California |
United States | Sutter Medical Center Sacramento | Sacramento | California |
United States | Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center | Saint Joseph | Michigan |
United States | Missouri Baptist Medical Center | 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 | Sainte Genevieve County Memorial Hospital | Sainte Genevieve | Missouri |
United States | California Pacific Medical Center-Pacific Campus | San Francisco | California |
United States | Kootenai Clinic Cancer Services - Sandpoint | Sandpoint | Idaho |
United States | Palo Alto Medical Foundation-Santa Cruz | Santa Cruz | California |
United States | Saint Vincent Hospital Cancer Center at Sheboygan | Sheboygan | Wisconsin |
United States | Avera Cancer Institute | Sioux Falls | South Dakota |
United States | Memorial Medical Center | Springfield | Illinois |
United States | Southern Illinois University School of Medicine | Springfield | Illinois |
United States | Springfield Clinic | Springfield | Illinois |
United States | Marshfield Medical Center-River Region at Stevens Point | Stevens Point | Wisconsin |
United States | Saint Vincent Hospital Cancer Center at Sturgeon Bay | Sturgeon Bay | Wisconsin |
United States | Missouri Baptist Sullivan Hospital | Sullivan | Missouri |
United States | Palo Alto Medical Foundation-Sunnyvale | Sunnyvale | California |
United States | BJC Outpatient Center at Sunset Hills | Sunset Hills | Missouri |
United States | Munson Medical Center | Traverse City | Michigan |
United States | Upper Valley Medical Center | Troy | Ohio |
United States | Carle Cancer Center | Urbana | Illinois |
United States | Sutter Solano Medical Center/Cancer Center | Vallejo | California |
United States | Marshfield Medical Center - Weston | Weston | Wisconsin |
United States | Asplundh Cancer Pavilion | Willow Grove | Pennsylvania |
United States | University of Michigan Health - West | Wyoming | Michigan |
United States | Rush-Copley Healthcare Center | Yorkville | Illinois |
Lead Sponsor | Collaborator |
---|---|
National Cancer Institute (NCI) |
United States, Canada,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Recurrence free survival (RFS) | Will evaluate RFS of single agent adjuvant nivolumab plus placebo compared to the combination treatment of adjuvant nivolumab plus cabozantinib in patients with resected mucosal melanoma. | Number of days from registration until either local or distant recurrence or death (due to any cause), assessed up to 5 years | |
Secondary | Overall survival (OS) | Will be evaluated utilizing the Kaplan-Meier (KM) method and, when appropriate, cox proportional hazards models. Median OS is calculated (along with 95% Confidence intervals) using the KM method. A Cox proportional hazards model is built to compare arms 1 and 2 with respect to OS. | Number of days from registration until death (due to any cause, assessed up to 5 years | |
Secondary | RFS | Median RFS will be calculated (along with 95% Confidence intervals) using the KM method. A Cox proportional hazards model will also be built to compare arms 1 and 2 with respect to RFS, with and without stratifying for PD-L1 categorization. For non-resected cohort, If a patient in this group has surgery, their PFS data will be censored at the time of surgery. | Number of days from registration until either local or distant recurrence or death (due to any cause), assessed up to 5 years | |
Secondary | Progression free survival (PFS) | Will be evaluated in multiple settings utilizing the KM method and, when appropriate, cox proportional hazards models. | Number of days from registration until either radiographic or clinical progression or death (due to any cause), assessed up to 5 years | |
Secondary | Overall response rate (Arm 3) | Up to 5 years | ||
Secondary | Duration of response (Arm 3) | A KM analysis is performed to calculate the median duration of response and 95% confidence intervals are constructed. | Time from the first evidence of response until progression, assessed up to 5 years | |
Secondary | Incidence of adverse events | The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events version 5.0. The frequency and percentage of grade 3+ adverse events will be summarized. | Up to 5 years |
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