Paclitaxel With or Without Pazopanib Hydrochloride in Treating Patients With Persistent or Recurrent Ovarian Epithelial, Fallopian Tube, or Peritoneal Cavity Cancer

Recurrent Ovarian Carcinoma Clinical Trial

Official title:

A Randomized Phase IIB Evaluation of Weekly Paclitaxel (NSC #673089) Plus Pazopanib (NSC #737754) Versus Weekly Paclitaxel Plus Placebo in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01468909
• Other study ID #: NCI-2011-03635
• Secondary ID: NCI-2011-03635CD
• Status: Completed
• Phase: Phase 2
• Start date: December 12, 2011
• Est. completion date: January 27, 2018

Study information

• Verified date: July 2019
• 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 paclitaxel when given together with or without pazopanib hydrochloride works in treating patients with ovarian epithelial, fallopian tube, or peritoneal cavity cancer that is persistent or has come back. Drugs used in chemotherapy, 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. Pazopanib hydrochloride may stop the growth of tumor cells by blocking blood flow to the tumor or by blocking some of the enzymes needed for cell growth. It is not yet known whether paclitaxel is more effective when given with or without pazopanib hydrochloride in treating ovarian epithelial, fallopian tube, and peritoneal cavity cancer.

Description:

PRIMARY OBJECTIVES:

I. To estimate the progression-free survival hazard ratio of the combination of weekly paclitaxel and pazopanib (pazopanib hydrochloride) compared to weekly paclitaxel and placebo in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer.

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 in Solid Tumors (RECIST), cancer antigen 125 (CA125) response, the overall survival (OS), and the duration of response in each arm.

TERTIARY OBJECTIVES:

I. To explore the association between plasma cytokines and angiogenic markers and progression-free and overall survival.

II. To explore the association between single-nucleotide polymorphisms (SNPs) and progression-free and overall survival.

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

ARM I: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15 and placebo orally (PO) daily on days 1-28.

ARM II: Patients receive paclitaxel as in Arm I and pazopanib hydrochloride PO daily on days 1-28.

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 106
• Est. completion date: January 27, 2018
• Est. primary completion date: January 27, 2018
• 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 in a patient is defined in this protocol as one who does not have measurable disease but has 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 Gynecology 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 who have received one prior regimen must have a GOG performance status of 0, 1, or 2

• Patients who have received two or three prior regimens must have a GOG performance status of 0 or 1

• Recovery from effects of recent surgery, radiotherapy, or chemotherapy

• 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 registration

• 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 registration; 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 registration

• At least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: laparotomy, laparoscopy, thoracotomy, video-assisted thorascopic surgery [VATS]); there is no restriction on minor procedures (e.g., minor: central venous access catheter placement, ureteral stent placement or exchange, paracentesis, thoracentesis)

• 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 can 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 platelet-derived growth factor (PDGF) pathways for management of recurrent or persistent disease

• For the purposes of this study, poly (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 1.5 x upper limit of normal (ULN) (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin)

• Partial thromboplastin time (PTT) less than or equal to 1.5 x ULN

• Creatinine less than or equal to 1.5 x institutional ULN

• Urine protein should be screened by urinalysis; if urine protein is 2+ or higher, 24-hour urine protein should be obtained and the level must be < 1000 mg (< 1.0 g/24 hours [hrs]) for patient enrollment

• Bilirubin less than or equal to 1.5 x ULN

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x ULN

• Subjects who have BOTH bilirubin greater than ULN and AST/ALT greater than ULN are not eligible

• Alkaline phosphatase less than or equal to 2.5 x ULN

• Patients must have normal baseline thyroid function tests (thyroid-stimulating hormone [TSH], T3, T4); a history of hypothyroidism and/or hyperthyroidism is allowed, as long as the patient has stable well-controlled thyroid function for a minimum of 2 months

• 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; 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 be capable of taking and absorbing oral medications; a patient must be clear of the following:

• Any lesion, whether induced by tumor, radiation, or other conditions, which makes it difficult to swallow tablets

• Prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel

• Active peptic ulcer disease

• Malabsorption syndrome

• Any concomitant medications that are associated with a risk of corrected QT (QTc) prolongation and/or Torsades de Pointes should be discontinued or replaced with drugs that do not carry these risks, if possible; patients who must take medication with a risk of possible risk of Torsades de Pointes should be watched carefully for symptoms of QTc prolongation, such as syncope

• Patients with personal or family history of congenital long QTc syndrome are NOT eligible

• Strong inhibitors of cytochrome P-450 system (CYP)3A4 are prohibited

• Strong inducers of CYP3A4 are prohibited

• Concomitant use of agents with narrow therapeutic windows that are metabolized by CYP3A4, CYP2D6, or CYP2C8 is not recommended

Exclusion Criteria:

• Patients who have had previous treatment with pazopanib; patients who have had 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 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; 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

• Patients with clinically significant cardiovascular disease; this includes:

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

• Congenital long QT syndrome or baseline QTc greater than 480 milliseconds

• 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

• Patients who have received prior treatment with an anthracycline (including doxorubicin and/or liposomal doxorubicin) must have an echocardiogram assessment and are excluded if they have an ejection fraction less than 50%

• CTCAE grade 2 or greater peripheral vascular disease (at least brief [less than 24 hours] episodes of ischemia managed non-surgically and without permanent deficit)

• History of cardiac angioplasty or stenting within 6 months prior to registration

• History of coronary artery bypass graft surgery within 6 months prior to registration

• Arterial thrombosis within 6 months prior to registration

• Patients with serious non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to the first date of study treatment

• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels

• 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, 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

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib

• Known human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy

• Patients with any condition that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation, including:

• Active peptic ulcer disease

• Known gastrointestinal intraluminal metastatic lesions (gastrointestinal serosa metastatic lesions are permitted)

• Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease)

• Patients with clinical symptoms or signs of gastrointestinal obstruction

• Patients who require parenteral hydration and/or nutrition

• Patients who are pregnant or nursing

• History of hemoptysis in excess of 2.5 mL (½ teaspoon) within 8 weeks prior to first dose of pazopanib

• Uncontrolled intercurrent illness including, but not limited to, psychiatric illness/social situations that would limit compliance with study requirements

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Ovarian Epithelial
• Fallopian Tube Neoplasms
• Ovarian Neoplasms
• Recurrent Fallopian Tube Carcinoma
• Recurrent Ovarian Carcinoma
• Recurrent Primary Peritoneal Carcinoma

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Paclitaxel
Given IV
• Pazopanib Hydrochloride
Given PO

Other:
• Placebo
Given PO

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	Women's Cancer Care Associates LLC	Albany	New York
United States	McFarland Clinic PC - Ames	Ames	Iowa
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	PeaceHealth Medical Group PC	Bellingham	Washington
United States	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
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	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati/Barrett Cancer Center	Cincinnati	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	Riverside Methodist Hospital	Columbus	Ohio
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Beaumont Hospital-Dearborn	Dearborn	Michigan
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	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
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	University of Connecticut	Farmington	Connecticut
United States	Hurley Medical Center	Flint	Michigan
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	Genesys Regional Medical Center	Grand Blanc	Michigan
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	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 Green Bay	Green Bay	Wisconsin
United States	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina
United States	Hartford Hospital	Hartford	Connecticut
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Sudarshan K Sharma MD Limted-Gynecologic Oncology	Hinsdale	Illinois
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
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	Allegiance Health	Jackson	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Freeman Health System	Joplin	Missouri
United States	Kettering Medical Center	Kettering	Ohio
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Sparrow Hospital	Lansing	Michigan
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
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	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Central Georgia Gynecologic Oncology	Macon	Georgia
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Lake University Ireland Cancer Center	Mentor	Ohio
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	Skagit Valley Hospital Regional Cancer Care Center	Mount Vernon	Washington
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Gynecologic Oncology Associates-Newport Beach	Newport Beach	California
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Florida Hospital Orlando	Orlando	Florida
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Gynecologic Oncology Group of Arizona	Phoenix	Arizona
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Maine Medical Center-Bramhall Campus	Portland	Maine
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 Clinic-Rice Lake Center	Rice Lake	Wisconsin
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Women's Cancer Associates	Saint Petersburg	Florida
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Memorial Health University Medical Center	Savannah	Georgia
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	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina
United States	Olympic Medical Cancer Care Center	Sequim	Washington
United States	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina
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	Ascension 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	Munson Medical Center	Traverse City	Michigan
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington
United States	Reading Hospital	West Reading	Pennsylvania
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	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Single-nucleotide Polymorphisms, Assessed Using the iPLEX Assay on the Sequenome MassARRAY Platform	Analyzed using deoxyribonucleic acid isolated from whole blood specimens.	Up to 5 years
Primary	Progression Free Survival	The time from randomization until disease progression, death, or date of last contact. Endpoints are progression or death. Patients who are not observed with an endpoint are censored. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	For those patients whose disease can be evaluated by physical examination, progression was assessed prior to each 21-day cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle, Up to 5 years
Secondary	Adverse Events as Assessed by CTCAE v.4	All grade 3 or greater Adverse Events (AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported.	From baseline to 30 days after last dose of drug.
Secondary	Proportion of Participants With Tumor Response by RECIST	Patients with Complete and Partial Tumor Response by RECIST 1.1. Responses (CR and PR) require confirmation at greater than or equal to 4 weeks from initial documentation. 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.	Every other cycle for 6 months, then every 3 months until disease progression,Up to 5 years
Secondary	Percentage of Participants With Tumor Response by CA-125	Response as evaluated by CA-125 levels. Response is indicated if CA-125 reduced by 50% of the baseline measure.	Prior to each cycle of treatment. Then follow-up every three months for 2 years and then every 6 months for 3 years, up to 5 years.
Secondary	Overall Survival (OS)	Overall survival	Every cycle while patient is receiving protocol therapy. Patients monitored for survival after off therapy every 3 months for 2 years, then every 6 months, up to 5 years