Cabozantinib or Paclitaxel in Treating Patients With Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cavity Cancer

Recurrent Ovarian Carcinoma Clinical Trial

Official title:

A Randomized Phase II Study of NCI Supplied Cabozantinib (NSC #761968) Versus Weekly Paclitaxel (NSC #673089) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01716715
• Other study ID #: NCI-2012-02058
• Secondary ID: NCI-2012-02058GO
• Status: Completed
• Phase: Phase 2
• Start date: November 6, 2012
• Est. completion date: February 9, 2019

Study information

• Verified date: February 2020
• 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 giving cabozantinib-s-malate or paclitaxel works in treating patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cavity cancer. 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 paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether cabozantinib-s-malate or paclitaxel is more effective at treating patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cavity cancer.

Description:

PRIMARY OBJECTIVES:

I. To assess the activity of cabozantinib (cabozantinib-s-malate) relative to weekly paclitaxel in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer with a log-rank test assessing progression-free survival (PFS) at 3.68 months (approximately pre-cycle 5) and 7.36 months (approximately pre-cycle 9).

SECONDARY OBJECTIVES:

I. To determine the frequency and severity of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE).

II. To estimate and compare the proportion of patients responding to therapy by Response Evaluation Criteria for Solid Tumors (RECIST), cancer antigen 125 (CA125) response, the overall survival (OS), and the duration of response in each arm.

TERTIARY OBJECTIVES:

I. To retrospectively correlate c-met proto-oncogene (MET) expression with overall outcome.

II. To retrospectively correlate c-MET copy number with overall outcome.

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.

ARM II: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 111
• Est. completion date: February 9, 2019
• Est. primary completion date: March 16, 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma; histologic documentation of the original primary tumor is required via the pathology report

• Patients must have measurable disease or non-measurable (detectable) disease:

• Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be greater than or equal to 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or greater than or equal to 20 mm when measured by chest x-ray; lymph nodes must be greater than or equal to 15 mm in short axis when measured by CT or MRI

• Non-measurable (detectable) disease is defined in this protocol as the absence of measurable disease but at least one of the following conditions:

• Ascites and/or pleural effusion attributed to tumor

• Solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions

• Patients with measurable disease must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

• Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG phase III or rare tumor protocol for the same patient population; in addition, patients must not be eligible for the currently active phase II cytotoxic protocol in platinum resistant disease

• Patients must have a GOG performance status of 0, 1, or 2

• Recovery from effects of recent surgery, radiotherapy, or chemotherapy to baseline or CTCAE =< grade 1 toxicity from all prior therapies except alopecia and other non-clinically significant adverse events (AE's):

• Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])

• Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to treatment

• Any other prior therapy directed at the malignant tumor, including chemotherapy, biological/targeted (non-cytotoxic) agents and immunologic agents, must be discontinued at least three weeks prior to treatment

• Chimeric or human or humanized monoclonal antibodies (including bevacizumab) or vascular endothelial growth factor (VEGF) receptor fusion proteins (including VEGF TRAP/aflibercept) must be discontinued for at least 12 weeks prior to treatment

• Investigational agents must be discontinued for at least 28 days prior to treatment

• Any prior radiation therapy must be discontinued at least four weeks prior to treatment

• Prior therapy

• Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, biologic/targeted (non-cytotoxic) agents (e.g., bevacizumab) or extended therapy administered after surgical or non-surgical assessment; if patients were treated with paclitaxel for their primary disease, this could have been given weekly or every 3 weeks

• Patients are allowed to receive, but are not required to receive, two additional cytotoxic regimens for management of recurrent or persistent disease, with no more than 1 non-platinum, non-taxane regimen; treatment with weekly paclitaxel for recurrent or persistent disease is NOT allowed

• Patients are allowed to receive, but are not required to receive, biologic/targeted (non-cytotoxic) therapy as part of their primary treatment regimen

• Patients must have NOT received any biologic/targeted (non-cytotoxic) therapy targeting the VEGF and/or MET pathways for management of recurrent or persistent disease

• For the purposes of this study, poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors will be considered "cytotoxic"; patients are allowed to receive, but are not required to receive, PARP inhibitors for management of primary or recurrent/persistent disease (either alone or in combination with cytotoxic chemotherapy); PARP inhibitors will NOT count as a prior regimen when given alone

• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl

• Platelets greater than or equal to 100,000/mcl

• Hemoglobin greater than or equal to 9 g/dL

• Prothrombin time (PT) such that international normalized ratio (INR) is less than or equal to 1.3 x institutional upper limit of normal (ULN)

• Partial thromboplastin time (PTT) less than or equal to 1.3 x ULN

• Creatinine less than or equal to 1.5 x ULN

• Phosphorus, corrected calcium, magnesium and potassium greater than or equal to institutional lower limit of normal (LLN)

• Urine protein creatinine (UPC) ratio must be < 1.0 gm; if UPC ratio >= 1, collection of 24-hour urine measurement of urine protein is recommended

• Bilirubin less than or equal to 1.5 x ULN

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x ULN

• Alkaline phosphatase less than or equal to 2.5 x ULN

• Albumin greater than or equal to 2.8 g/dL

• Lipase less than or equal to 2 x ULN

• No radiologic or clinical evidence of pancreatitis

• Patients must have a normal baseline thyroid stimulating hormone (TSH); a history of hypothyroidism and/or hyperthyroidism is allowed

• Neuropathy (sensory and motor) less than or equal to grade 1

• Patients of childbearing potential must have a negative pregnancy test prior to the study entry and be practicing an effective form of contraception; sexually active subjects must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 4 months after the last dose of study drug, even if oral contraceptives are also used; all subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug; pregnant women are excluded from this study

• Patients must have signed an approved informed consent and authorization permitting the release of personal health information

• Patients must meet pre-entry requirements

Exclusion Criteria:

• Patients who have had previous treatment with cabozantinib; patients who have received previous treatment with weekly paclitaxel for recurrent or persistent disease

• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy

• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis or thoracic cavity within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease

• Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease

• Uncontrolled hypertension, defined as systolic greater than 140 mm Hg or diastolic greater than 90 mm Hg despite antihypertensive medications

• Myocardial infarction or unstable angina within 6 months prior to registration

• New York Heart Association (NYHA) class II or greater congestive heart failure

• History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or serious cardiac arrhythmia requiring medication; this does not include asymptomatic atrial fibrillation with controlled ventricular rate

• Any history of congenital long QT syndrome

• The subject has 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 electrocardiogram (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

• Patients with serious non-healing wound, ulcer, or bone fracture within 28 days before treatment

• Patients with history of organ transplant

• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving (in contact with, invading or encasing) major vessels

• Patients who have experienced any of the following:

• Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment

• Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment

• Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment

• Patients who have radiographic evidence of cavitating pulmonary lesion(s)

• Patients who have 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 treatment

• Gastrointestinal disorders, particularly those with potential risk of perforation or fistula formation including:

• Any of the following within 28 days of registration

• 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 6 months of registration

• Abdominal fistula

• Gastrointestinal perforation

• Bowel obstruction or gastric outlet obstruction; note: patients requiring drainage gastrostomy (e.g., percutaneous endoscopic gastrostomy [PEG] tube) and/or parenteral hydration and/or nutrition are not eligible

• Intra-abdominal abscess; note: complete resolution of an intra-abdominal abscess must be confirmed prior to registration even if the abscess occurred more than 6 months prior to registration

• Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures which are not controlled with non-enzyme inducing anticonvulsants, any brain metastases and/or epidural disease, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months prior to the first date of study treatment

• The subject requires chronic concomitant treatment of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort)

• Patients who are unable or unwilling to swallow tablets

• Patients who are pregnant or nursing

• The subject requires concomitant treatment, in therapeutic doses, with anti-coagulants such as warfarin or warfarin-related agents, heparin, thrombin or factor Xa inhibitors or antiplatelet agents (i.e. clopidogrel); low dose aspirin (=< 81 mg/day) low-dose warfarin (=< 1 mg/day) and prophylactic low molecular weight heparin are permitted

• Major surgery within 3 months of the first dose of cabozantinib if there were no wound healing complications or within 6 months of the first dose of cabozantinib if there were wound complications

• Minor surgery within 1 month of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications

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

Related Conditions & MeSH terms

• Carcinoma
• Recurrent Fallopian Tube Carcinoma
• Recurrent Ovarian Carcinoma
• Recurrent Primary Peritoneal Carcinoma

Intervention

Drug:
• Cabozantinib S-malate
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Paclitaxel
Given IV

Locations

Country	Name	City	State
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio
United States	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic PC - Ames	Ames	Iowa
United States	University of Colorado Hospital	Aurora	Colorado
United States	Woman's Hospital	Baton Rouge	Louisiana
United States	PeaceHealth Medical Group PC	Bellingham	Washington
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	McFarland Clinic PC-Boone	Boone	Iowa
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
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	Adena Regional Medical Center	Chillicothe	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Columbus NCI Community Oncology Research Program	Columbus	Ohio
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	John Muir Medical Center-Concord Campus	Concord	California
United States	Miami Valley Hospital	Dayton	Ohio
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Delaware Radiation Oncology	Delaware	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	HSHS Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Sanford Clinic North-Fargo	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Baylor All Saints Medical Center at Fort Worth	Fort Worth	Texas
United States	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia
United States	Hartford Hospital	Hartford	Connecticut
United States	Sudarshan K Sharma MD Limited-Gynecologic Oncology	Hinsdale	Illinois
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Lyndon Baines Johnson General Hospital	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Saint Dominic-Jackson Memorial Hospital	Jackson	Mississippi
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	McFarland Clinic PC-Jefferson	Jefferson	Iowa
United States	Freeman Health System	Joplin	Missouri
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Lancaster Radiation Oncology	Lancaster	Ohio
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Beebe Medical Center	Lewes	Delaware
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Cancer Center of Kansas-Manhattan	Manhattan	Kansas
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	McFarland Clinic PC-Marshalltown	Marshalltown	Iowa
United States	Marshfield Medical Center	Marshfield	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	NYU Winthrop Hospital	Mineola	New York
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Skagit Valley Hospital Regional Cancer Care Center	Mount Vernon	Washington
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	The Hospital of Central Connecticut	New Britain	Connecticut
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	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Newark Radiation Oncology	Newark	Ohio
United States	Gynecologic Oncology Associates-Newport Beach	Newport Beach	California
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Maine Medical Center-Bramhall Campus	Portland	Maine
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Maine Medical Center- Scarborough Campus	Scarborough	Maine
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Northwest Hospital	Seattle	Washington
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Olympic Medical Cancer Care Center	Sequim	Washington
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Rockwood Cancer Treatment Center-DHEC-Downtown	Spokane	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
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	Springfield Regional Medical Center	Springfield	Ohio
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Saint Joseph Medical Center	Tacoma	Washington
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Wichita NCI Community Oncology Research Program	Wichita	Kansas
United States	New Hanover Regional Medical Center/Zimmer Cancer Center	Wilmington	North Carolina
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	University of Massachusetts Memorial Health Care	Worcester	Massachusetts
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	c-Met Expression		Baseline
Other	c-MET Copy Number		Baseline
Primary	Event Free Survival	Time from patient entry until progression, death, or beginning a subsequent therapy. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.",	The duration of time from study entry to time to progression or death,or begining a subsequent therapy, whichever occurs first, assessed up to 32 weeks
Secondary	Number of Participants With Grade 3 or Higher Adverse Events by Type	Toxicities will be characterized by their frequency and severity, grade 3 and above.	Up to 30 days after completion of study treatment
Secondary	Response, Assessed According to RECIST Version 1.1	Complete and Partial Tumor Response by RECIST. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR	CT or MRI used to follow lesion every 8 weeks for the first 8 months, then every 12 weeks until disease progression, approximately 2.5 years
Secondary	Percentage of Participants With CA125 Response.	Complete and Partial Tumor Response by CA125. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.",	Prior to each cycle of treatment. Then follow-up every 3 months for 2 years then then every 6 months, up to 2.5 years.
Secondary	Overall Survival	The time from randomization until death or date of last contact. Endpoint is death. Patients who are not observed with an endpoint are censored.	The duration of time from study entry to time of death or the date of last contact, an average of 2.5 years.
Secondary	To Estimate the Response Duration Among Patients Who Respond.	The time participant is in response.Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.",	From the time measurement criteria are met for CR or PR until the first date that recurrent or progressive disease is objectively documented or date of death from any cause, whichever came first, assessed up to 18 months.