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Gynecologic Cancer

Paclitaxel With or Without Pazopanib in Persistent or Recurrent Ovarian Epithelial, Fallopian Tube, or Peritoneal Cavity Cancer (GOG 186-J)
A Randomized Phase II Evaluation of Weekly Paclitaxel (NSC #673089) Plus Pazopanib (NSC #737754) (IND #75648) Versus Weekly Paclitaxel Plus Placebo in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma
Status Conditions Phase Study ID
Recruiting Ovarian Epithelial Cancer
Fallopian Tube Cancer
Peritoneal Cavity Cancer
II GOG 186-J
NCT01468909
Summary

The primary objective of this study is to estimate the progression-free survival hazard ratio of the combination of weekly paclitaxel and pazopanib hydrochloride compared to weekly paclitaxel and placebo in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer.


Investigator
Benjamin Greer, MD
Location    
PSOC Office 206-667-5152  
Multicare Health System, Tacoma WA 253-403-5265  
Olympic Medical Center, Sequim WA 360-683-9895  
Skagit Valley Hospital, Mt. Vernon WA 360-424-2687  
Wenatchee Valley Medical Center, Wenatchee WA 509-665-5800 x5122  
Group Health 206-225-7893  
Eligibility Criteria (must meet the following to participate in this study)
  • 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 CT, 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
      • 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
    • 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
  • Patients must not be eligible for a higher priority GOG protocol, if one exists

    • Patients must not be eligible for a currently active, phase II cytotoxic protocol in platinum-resistant disease
  • 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
    • Treatment with weekly paclitaxel for recurrent or persistent disease is NOT allowed
  • No history or evidence upon physical examination of CNS disease, including primary brain tumor or any brain metastases

PATIENT CHARACTERISTICS:

  • 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
  • Absolute neutrophil count (ANC) greater than or equal to 1,500/µL
  • Platelets greater than or equal to 100,000/µL
  • Hemoglobin greater than or equal to 9 g/dL
  • Creatinine less than or equal to 1.5 x institutional upper limit of normal (ULN)
  • PT such that international normalized ratio (INR) is less than or equal to 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin)
  • PTT less than or equal to 1.5 x ULN
  • If urine protein is 2+ or higher, 24-hour urine protein should be obtained and the level must be < 1000 mg (<1.0 g/24hrs) for patient enrollment
  • Bilirubin less than or equal to 1.5 x ULN
  • AST and 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 (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 should be free of active infection requiring antibiotics (with the exception of uncomplicated UTI)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use an effective form of contraception
  • Patients must be capable of taking and absorbing oral medications and be clear of the following:

    • Any lesion, whether induced by tumor, radiation, or other conditions, that makes it difficult to swallow tablets
    • Active peptic ulcer disease
    • Malabsorption syndrome
Exclusions (conditions that would prevent participation in this study)
  • Patients with personal or family history of congenital long QTc syndrome are NOT eligible
  • 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
  • No clinically significant cardiovascular disease including any of the following:

    • 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 hrs) 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
  • No serious non-healing wound, ulcer, or bone fracture

    • Includes history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to the first date of study treatment
  • No patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
  • No seizures that are not controlled with non-enzyme-inducing anticonvulsants
  • No 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
  • No known HIV-positive subjects on combination antiretroviral therapy
  • No 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 disease)
    • Patients with clinical symptoms or signs of gastrointestinal obstruction
    • Patients who require parenteral hydration and/or nutrition
  • No history of hemoptysis in excess of 2.5 mL (½ teaspoon) within 8 weeks prior to first dose of pazopanib
  • No uncontrolled intercurrent illness including, but not limited to, psychiatric illness/social situations that would limit compliance with study requirements
  • See Disease Characteristics
  • Recovered from effects of recent surgery, radiotherapy, or chemotherapy
  • 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

    • No previous treatment with weekly paclitaxel for recurrent or persistent disease
    • No previous cancer treatment that contraindicates this protocol therapy
  • Patients are allowed to receive, but are not required to receive, biologic/targeted (non-cytotoxic) therapy as part of their primary treatment regimen
  • Patients are allowed to receive, but are not required to receive, poly (ADP-ribose) polymerase (PARP) inhibitors for management of primary or recurrent/persistent disease (either alone or in combination with cytotoxic chemotherapy)

    • For the purposes of this study, PARP inhibitors will be considered "cytotoxic"
    • PARP inhibitors will NOT count as a prior regimen when given alone
  • 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 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, or video-assisted thorascopic surgery [VATS])

    • No prior surgical procedures affecting absorption including, but not limited to, major resection of stomach or small bowel
    • There is no restriction on minor procedures (e.g., central venous access catheter placement, ureteral stent placement or exchange, paracentesis, or thoracentesis)
  • Patients must have NOT received any biologic/targeted (non-cytotoxic) therapy targeting the VEGF and/or PDGF pathways for management of recurrent or persistent disease
  • Any concomitant medications that are associated with a risk of QTc prolongation and/or Torsades de Pointes should be discontinued or replaced with drugs that do not carry these risks, if possible
  • Strong inhibitors of CYP3A4 are prohibited
  • Strong inducers of CYP3A4 are prohibited
  • No previous treatment with pazopanib
  • No prior radiotherapy to any portion of the abdominal cavity or pelvis within the last three years

    • 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
  • No 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
  • Grapefruit juice and St. John wort are not allowed on this study
Last Updated
March 01, 2013
See this trial at ClinicalTrials.gov
Access protocol and consent forms at Fred Hutchinson Cancer Research Center
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Please remember:
  • Talk to your health care providers first before making decisions about your health care.
  • Whether you are eligible for a research study depends on many things. There are specific requirements to be in research studies. These requirements are different for each study.