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

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

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Placebo; Drug: Pazopanib Hydrochloride; Drug: Paclitaxel

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36688
      • University of South Alabama Mitchell Cancer Institute
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Gynecologic Oncology Group of Arizona
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • Newport Beach, California, United States, 92663
      • Gynecologic Oncology Associates-Newport Beach
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut
    • Hartford, Connecticut, United States, 06105
      • Smilow Cancer Hospital Care Center at Saint Francis
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • Florida
    • Orlando, Florida, United States, 32803
      • Florida Hospital Orlando
    • Saint Petersburg, Florida, United States, 33701
      • Women's Cancer Associates
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center-Gainesville
    • Macon, Georgia, United States, 31201
      • Central Georgia Gynecologic Oncology
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Hinsdale, Illinois, United States, 60521
      • Sudarshan K Sharma MD Limted-Gynecologic Oncology
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46260
      • Saint Vincent Hospital and Health Care Center
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic PC - Ames
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50309
      • Iowa-Wide Oncology Research Coalition NCORP
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates-Laurel
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Liberal, Kansas, United States, 67905
      • Cancer Center of Kansas-Liberal
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas - Pratt
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
    • Wichita, Kansas, United States, 67208
      • Associates In Womens Health
    • Wichita, Kansas, United States, 67214
      • Wichita NCI Community Oncology Research Program
    • Wichita, Kansas, United States, 67214
      • Via Christi Regional Medical Center
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center-Bramhall Campus
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
    • Elkton, Maryland, United States, 21921
      • Union Hospital of Cecil County
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Saint Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium NCORP
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Big Rapids, Michigan, United States, 49307
      • Spectrum Health Big Rapids Hospital
    • Dearborn, Michigan, United States, 48124
      • Beaumont Hospital-Dearborn
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Grand Blanc, Michigan, United States, 48439
      • Genesys Regional Medical Center
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Grand Rapids, Michigan, United States, 49503
      • Cancer Research Consortium of West Michigan NCORP
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
    • Livonia, Michigan, United States, 48154
      • Saint Mary Mercy Hospital
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Lake Huron Medical Center
    • Saginaw, Michigan, United States, 48601
      • Saint Mary's of Michigan
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Joplin, Missouri, United States, 64804
      • Freeman Health System
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Springfield, Missouri, United States, 65804
      • Cancer Research for the Ozarks NCORP
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Women's Cancer Center of Nevada
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Women's Cancer Care Associates LLC
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Akron City Hospital/Cooper Cancer Center
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati/Barrett Cancer Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Mentor, Ohio, United States, 44060
      • Lake University Ireland Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists and Research Institute-Tulsa
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania/Abramson Cancer Center
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Faris
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System Cancer Institute-Eastside
    • Seneca, South Carolina, United States, 29672
      • Greenville Health System Cancer Institute-Seneca
    • Spartanburg, South Carolina, United States, 29307
      • Greenville Health System Cancer Institute-Spartanburg
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
    • Fort Worth, Texas, United States, 76104
      • Baylor All Saints Medical Center at Fort Worth
  • Washington
    • Bellingham, Washington, United States, 98226
      • PeaceHealth Medical Group PC
    • Bremerton, Washington, United States, 98310
      • Harrison HealthPartners Hematology and Oncology-Bremerton
    • Bremerton, Washington, United States, 98310
      • Harrison Medical Center
    • Everett, Washington, United States, 98201
      • Providence Regional Cancer Partnership
    • Mount Vernon, Washington, United States, 98273
      • Skagit Valley Hospital Regional Cancer Care Center
    • Poulsbo, Washington, United States, 98370
      • Harrison HealthPartners Hematology and Oncology-Poulsbo
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98112
      • Kaiser Permanente Washington
    • Seattle, Washington, United States, 98104
      • Pacific Gynecology Specialists
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98133
      • Northwest Hospital
    • Sequim, Washington, United States, 98384
      • Olympic Medical Cancer Care Center
    • Spokane, Washington, United States, 99204
      • Rockwood Cancer Treatment Center-DHEC-Downtown
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Tacoma, Washington, United States, 98405
      • MultiCare Tacoma General Hospital
    • Tacoma, Washington, United States, 98405
      • Saint Joseph Medical Center
    • Walla Walla, Washington, United States, 99362
      • Providence Saint Mary Regional Cancer Center
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital and Clinics
  • Wisconsin
    • Eau Claire, Wisconsin, United States, 54701
      • Marshfield Clinic Cancer Center at Sacred Heart
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital Cancer Center Green Bay
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology Limited at Saint Mary's Hospital
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology at Saint Vincent Hospital
    • Manitowoc, Wisconsin, United States, 54221
      • Holy Family Memorial Hospital
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Medical Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Clinic-Minocqua Center
    • Rhinelander, Wisconsin, United States, 54501
      • Ascension Saint Mary's Hospital
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Clinic-Rice Lake Center
    • Stevens Point, Wisconsin, United States, 54481
      • Ascension Saint Michael's Hospital
    • Weston, Wisconsin, United States, 54476
      • Marshfield Clinic - Weston Center
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Marshfield Clinic - Wisconsin Rapids Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm I (paclitaxel and placebo); Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and placebo PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Placebo; Given PO; Other Names: placebo therapy; PLCB; sham therapy; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat
Experimental: Arm II (paclitaxel and pazopanib hydrochloride); Patients receive paclitaxel as in arm I and pazopanib hydrochloride PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Pazopanib Hydrochloride; Given PO; Other Names: GW786034B; Votrient; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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
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.
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: NRG Oncology
• Investigators: Principal Investigator: Debra Richardson, NRG Oncology

Publications and helpful links

General Publications

• Richardson DL, Sill MW, Coleman RL, Sood AK, Pearl ML, Kehoe SM, Carney ME, Hanjani P, Van Le L, Zhou XC, Alvarez Secord A, Gray HJ, Landrum LM, Lankes HA, Hu W, Aghajanian C. Paclitaxel With and Without Pazopanib for Persistent or Recurrent Ovarian Cancer: A Randomized Clinical Trial. JAMA Oncol. 2018 Feb 1;4(2):196-202. doi: 10.1001/jamaoncol.2017.4218.

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2011
• Primary Completion (Actual): January 27, 2018
• Study Completion (Actual): January 27, 2018

Study Registration Dates

• First Submitted: November 8, 2011
• First Submitted That Met QC Criteria: November 8, 2011
• First Posted (Estimate): November 10, 2011

Study Record Updates

• Last Update Posted (Actual): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 22, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Carcinoma; Recurrence; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: NCI-2011-03635 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180868 (U.S. NIH Grant/Contract); U10CA027469 (U.S. NIH Grant/Contract); CDR0000716028; GOG-0186J (Other Identifier: CTEP)