Cabozantinib-S-Malate Compared With Temozolomide or Dacarbazine in Treating Patients With Metastatic Melanoma of the Eye That Cannot Be Removed by Surgery

Stage IV Uveal Melanoma AJCC v7 Clinical Trial

Official title:

Randomized Phase II Study Comparing the MET Inhibitor Cabozantinib to Temozolomide/Dacarbazine in Ocular Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01835145
• Other study ID #: NCI-2013-00821
• Secondary ID: NCI-2013-00821CA
• Status: Completed
• Phase: Phase 2
• Start date: July 31, 2013
• Est. completion date: November 1, 2019

Study information

• Verified date: August 2022
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial studies how well cabozantinib-s-malate works compared with temozolomide or dacarbazine in treating patients with melanoma of the eye (ocular melanoma) that has spread to other parts of the body and cannot be removed by surgery. Cabozantinib-s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide and dacarbazine, 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. It is not yet known whether cabozantinib-s-malate works better than temozolomide or dacarbazine in treating patients with melanoma of the eye.

Description:

PRIMARY OBJECTIVES:

I. Compare the progression-free survival rate at 4 months (PFS4) of patients with ocular melanoma treated with cabozantinib-s-malate (cabozantinib) or temozolomide (or dacarbazine).

SECONDARY OBJECTIVES:

I. Estimate the distribution of progression-free survival (PFS) times. II. Estimate the distribution of overall survival (OS) times. III. Estimate the confirmed response rate as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

IV. Assess the safety of these agents by examining the toxicity profile. V. Correlate the response of MET molecular status.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cabozantinib-s-malate orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive temozolomide PO daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. If temozolomide is not available, patients receive dacarbazine intravenously (IV) over 15-60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for 2 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: November 1, 2019
• Est. primary completion date: October 21, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed uveal melanoma that is metastatic or unresectable; if histologic or cytologic confirmation of the primary is not available, confirmation of the primary diagnosis of uveal melanoma by the treating investigator can be clinically obtained, as per standard practice for uveal melanoma; pathologic confirmation of diagnosis will be performed at the participating site

• Measurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan or magnetic resonance imaging (MRI)

• Prior systemic therapies allowed, except for those treatments directed toward, or with activity against, c-Met or vascular endothelial growth factor/receptor (VEGF/R), and the chemotherapy agents temozolomide and dacarbazine; prior treatment must have been no earlier than 3 weeks prior to starting treatment with cabozantinib with exceptions noted below and the following: at least 4 weeks since prior hepatic infusion or at least 2 weeks since radiation therapy

• No cytotoxic chemotherapy including investigational cytotoxic chemotherapy or biologic agents (e.g., cytokines or antibodies) within the last 3 weeks, or nitrosoureas/mitomycin C within 6 weeks before the first dose of study treatment; at least 6 weeks must have elapsed if the last regimen included an anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) antibody; patients must have experienced disease progression on their prior therapy in the opinion of the treating investigator

• No prior radiation therapy within the last 4 weeks, except as below

• To the thoracic cavity, abdomen, or pelvis within 12 weeks before the first dose of study treatment, or has ongoing complications, or is without complete recovery to < grade 1 toxicity

• To bone or brain metastasis within 14 days before the first dose of study treatment

• To any other site(s) within 28 days before the first dose of study treatment

• Prior radiation treatment may have included no more than 3000 centigray (cGy) to fields including substantial bone marrow

• No prior radionuclide treatment within 6 weeks of the first dose of study treatment

• No prior treatment with a small molecule kinase inhibitor or a hormonal therapy within 14 days or 5 half-lives (whichever is longer)

• No concomitant anti-cancer therapy unless specified above

• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

• A corrected QT interval calculated by the Fridericia formula (QTcF) =< 500 ms within 28 days before randomization; Note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the patient meets eligibility in this regard

• Common Terminology Criteria for Adverse Events (CTCAE) recovered to baseline or CTCAE =< grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant adverse events (AEs)

• No active brain metastases or epidural disease; patients with brain metastases previously treated with whole brain radiation or radiosurgery or patients with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible; neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 12 weeks before starting study treatment; baseline brain imaging with contrast-enhanced CT or MRI scans for patients with known brain metastases is required to confirm eligibility

• No clinically significant gastrointestinal bleeding within 24 weeks before the first dose of study treatment

• No hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 12 weeks before the first dose of study treatment

• No signs indicative of pulmonary hemorrhage within 12 weeks before the first dose of study treatment

• No prior radiographic evidence of cavitating pulmonary lesion(s)

• No tumor in contact with, invading or encasing any major blood vessels

• No evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of treatment

• The patient may not have uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:

• Cardiovascular disorders including:

• Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening

• Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mmHg systolic, or > 90 mmHg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment

• Any history of congenital long QT syndrome

• Any of the following within 24 weeks before the first dose of study treatment:

• Unstable angina pectoris

• Clinically-significant cardiac arrhythmias

• Stroke (including transient ischemic attack [TIA], or other ischemic event)

• Myocardial infarction

• Thromboembolic event requiring therapeutic anticoagulation (Note:

patients with a venous filter [e.g. vena cava filter] are not eligible for this study)

• Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:

• Any of the following within 28 days before the first dose of study treatment

• Intra-abdominal tumor/metastases invading GI mucosa

• Active peptic ulcer disease

• Inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis

• Malabsorption syndrome

• Any of the following within 24 weeks before the first dose of study treatment:

• Abdominal fistula

• Gastrointestinal perforation

• Intra-abdominal abscess; Note: complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more that 24 weeks before the first dose of study treatment

• Bowel obstruction or gastric outlet obstruction

• Other clinically significant disorders such as:

• Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment

• History of organ transplant

• Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment

• History of major surgery as follows:

• Major surgery in past 8 weeks of the first dose of cabozantinib if there were no wound healing complications or within 24 weeks of the first dose of cabozantinib if there were wound complications

• Minor surgery within 4 weeks of the first dose of cabozantinib if there were no wound healing complications or within 12 weeks of the first dose of cabozantinib if there were wound complications

• In addition, complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of cabozantinib irrespective of the time from surgery

• Active infection requiring systemic treatment within 28 days before the first dose of study treatment

• No concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel); low dose aspirin (=< 81 mg/day), low-dose warfarin (=< 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted; please note that drugs that strongly induce or inhibit cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) or are associated with a risk of Torsades are not allowed; chronic concomitant treatment of CYP3A4 inducers is not allowed (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort); as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product; the following drugs are strong inhibitors of CYP3A4 and are not allowed during the treatment with cabozantinib:

• Boceprevir

• Indinavir

• Nelfinavir

• Lopinavir/ritonavir

• Saquinavir

• Telaprevir

• Ritonavir

• Clarithromycin

• Conivaptan

• Itraconazole

• Ketoconazole

• Mibefradil

• Nefazodone

• Posaconazole

• Voriconazole

• Telithromycin

• Drugs with possible or conditional risk of torsades should be used with caution knowing that cabozantinib could prolong the QT interval

• Patients who are pregnant or nursing are not eligible; women of child bearing potential must have a negative serum or urine pregnancy test within 16 days prior to registration; women of child-bearing potential include:

• Any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >= 12 consecutive months)

• Women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35m IU/mL

• Women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy)

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib, temozolomide and dacarbazine

• Absolute neutrophil count >= 1,500/mcL

• Platelets >= 100,000/mcL

• Total bilirubin =< 1.5 × upper limit of normal (ULN)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5.0 × institutional upper limit of normal (for patients with metastases); AST (SGOT)/ALT (SGPT) =< 2.5 × institutional upper limit of normal (for patients without metastases)

• Serum creatinine =< 1.5 × ULN, OR calculated creatinine clearance >= 30 mL/minute (modified Cockcroft and Gault formula)

• Hemoglobin >= 9 g/dL

• Serum albumin >= 2.8 g/dL

• Urine protein/creatinine ratio (UPCR) =< 1; if urine/protein creatinine (UPC) >= 1, then a 24-hour urine protein must be assessed; eligible patients must have a 24-hour urine protein value < 1 g/L

• Thyroid-stimulating hormone (TSH) within normal limits (WNL); supplementation is acceptable to achieve a TSH WNL; in patients with abnormal TSH however free T4 and free thyroxine index (FTI) are normal and patient is clinically euthyroid, patient is eligible

• Prothrombin time (PT)/international normalized ratio (INR) must be =< 1.2 x the laboratory ULN

• No clinical or radiographic evidence of pancreatitis

Related Conditions & MeSH terms

• Melanoma
• Recurrent Uveal Melanoma
• Stage III Uveal Melanoma AJCC v7
• Stage IIIA Uveal Melanoma AJCC v7
• Stage IIIB Uveal Melanoma AJCC v7
• Stage IIIC Uveal Melanoma AJCC v7
• Stage IV Uveal Melanoma AJCC v7
• Uveal Neoplasms

Intervention

Drug:
• Cabozantinib S-malate
Given PO
• Dacarbazine
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Temozolomide
Given PO

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic PC - Ames	Ames	Iowa
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Cancer Care Center at Island Hospital	Anacortes	Washington
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Anchorage Radiation Therapy Center	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Swedish Cancer Institute-Eastside Oncology Hematology	Bellevue	Washington
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Saint Charles Health System	Bend	Oregon
United States	Constantinou, Costas L MD (UIA Investigator)	Bettendorf	Iowa
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	McFarland Clinic PC-Boone	Boone	Iowa
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Bristol Regional Medical Center	Bristol	Tennessee
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	The Christ Hospital	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Big Horn Basin Cancer Center	Cody	Wyoming
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Bay Area Hospital	Coos Bay	Oregon
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Duke University Medical Center	Durham	North Carolina
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	McFarland Clinic PC-Trinity Cancer Center	Fort Dodge	Iowa
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
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	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Cancer and Blood Specialists-Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	GenesisCare USA - Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	Hematology Oncology Associates of Illinois-Highland Park	Highland Park	Illinois
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	McFarland Clinic PC-Jefferson	Jefferson	Iowa
United States	Wellmont Medical Associates Oncology and Hematology-Johnson City	Johnson City	Tennessee
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Jupiter Medical Center	Jupiter	Florida
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Presence Saint Mary's Hospital	Kankakee	Illinois
United States	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Ballad Health Cancer Care - Kingsport	Kingsport	Tennessee
United States	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee
United States	Vidant Oncology-Kinston	Kinston	North Carolina
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada
United States	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	GenesisCare USA - Fort Apache	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
United States	GenesisCare USA - Vegas Tenaya	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada
United States	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Beebe Medical Center	Lewes	Delaware
United States	Liberty Radiation Oncology Center	Liberty	Missouri
United States	AMG Libertyville - Oncology	Libertyville	Illinois
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	McFarland Clinic PC-Marshalltown	Marshalltown	Iowa
United States	Loyola University Medical Center	Maywood	Illinois
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Community Medical Hospital	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Garneau, Stewart C MD (UIA Investigator)	Moline	Illinois
United States	Porubcin, Michael MD (UIA Investigator)	Moline	Illinois
United States	Spector, David MD (UIA Investigator)	Moline	Illinois
United States	Trinity Medical Center	Moline	Illinois
United States	Morristown Medical Center	Morristown	New Jersey
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Christiana Gynecologic Oncology LLC	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Illinois Cancer Specialists-Niles	Niles	Illinois
United States	Lakeland Hospital Niles	Niles	Michigan
United States	Southwest VA Regional Cancer Center	Norton	Virginia
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	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Saint Joseph Oncology Inc	Saint Joseph	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
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	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Minor and James Medical PLLC	Seattle	Washington
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin
United States	Providence Regional Cancer System-Shelton	Shelton	Washington
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Downtown	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Valley	Spokane Valley	Washington
United States	Cancer Research for the Ozarks NCORP	Springfield	Missouri
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Overlook Hospital	Summit	New Jersey
United States	Munson Medical Center	Traverse City	Michigan
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Compass Oncology Vancouver	Vancouver	Washington
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
United States	Providence Regional Cancer System-Yelm	Yelm	Washington

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Exelisis

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pre-treatment GNAQ/GNA11 and Potentially Other Mutations in Tissue	The proportions of patients within these groups pre-treatment will be presented with 90% exact binomial confidence intervals. These findings will be correlated with overall survival using a Student's T-test.	Baseline
Other	Pre-treatment Immune Gene Expression in Tissue Defined as T Cell-inflamed, Intermediate and Non-T Cell-inflamed	The proportions of patients within these groups pre-treatment will be presented with 90% exact binomial confidence intervals. These findings will be correlated with overall survival using a Student's T-test.	Baseline
Primary	Proportion of Patients Without a Progression Free Survival Event at 4 Months (PFS4)	A patient will be declared a PFS4 success if they are on study and progression free for at least 4 months. Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, with an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. The success for each arm will be calculated independently as the number of successes divided by the total number of evaluable patients. A one-sided chi-squared test for a difference in PFS4 proportions will be used to test for a difference between arms.	At 4 months
Secondary	Confirmed Response Rate as Determined by the RECIST Criteria (Version 1.1)	The confirmed response rates will be estimated by dividing the number of confirmed responders by the number of evaluable patients. 95% confidence intervals will be calculated.	Up to 2 years
Secondary	Percentage of Patients Who Experienced Grade 3+ Adverse Events Regardless of Attribution	percentage of patients who experienced grade 3+ adverse events regardless of attribution, graded according to the National Cancer Institute CTCAE version 4.0	Up to 2 years
Secondary	Overall Survival (OS)	The distribution of OS time will be estimated using the method of Kaplan Meier.	Number of days from registration until death, assessed up to 2 years
Secondary	PFS	The distribution of PFS time will be estimated using the method of Kaplan Meier and is defined as the number of days from registration until disease progression (or death). Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, with an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.	Number of days from registration until disease progression (or death), assessed up to 2 years