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Bevacizumab With or Without Everolimus in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Genentech, Inc.
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Gynecologic Oncology Group
ClinicalTrials.gov Identifier:
NCT00886691
First received: April 22, 2009
Last updated: May 28, 2013
Last verified: May 2013
  Purpose

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and everolimus may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether bevacizumab is more effective when given together with or without everolimus in treating ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.

PURPOSE: This randomized phase II trial is studying bevacizumab to see how well it works when given with or without everolimus in treating patients with recurrent or persistent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.


Condition Intervention Phase
Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cavity Cancer
Biological: bevacizumab
Drug: everolimus
Other: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Double-Blinded Evaluation of Oral Everolimus (RAD001) Plus Bevacizumab vs. Oral Placebo Plus Bevacizumab in the Treatment of Recurrent or Persistent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Resource links provided by NLM:


Further study details as provided by Gynecologic Oncology Group:

Primary Outcome Measures:
  • Progression-free survival hazard ratio [ Designated as safety issue: No ]
  • Frequency and severity of adverse events as assessed by CTCAE v4.0 [ Designated as safety issue: Yes ]
  • Comparison of progression-free and overall survival of patients with measurable disease vs those with detectable (non-measurable) disease [ Designated as safety issue: No ]
  • Frequency of objective tumor response in patients with measurable disease [ Designated as safety issue: No ]
  • Frequency of CA-125 response [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: December 2010
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral everolimus once daily on days 1-28.
Biological: bevacizumab
Given IV
Drug: everolimus
Given orally
Experimental: Arm II
Patients receive bevacizumab as in arm I and oral placebo once daily on days 1-28.
Biological: bevacizumab
Given IV
Other: placebo
Given orally

Detailed Description:

OBJECTIVES:

Primary

  • To compare the progression-free survival hazard ratio in patients with persistent or recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer treated with bevacizumab with vs without everolimus.

Secondary

  • To determine the nature and degree of toxicity of these regimens.
  • To compare the progression-free and overall survival of patients with measurable disease vs those with detectable (non-measurable) disease.
  • To estimate the proportion of patients with measurable disease who have objective tumor response to treatment.
  • To provide descriptive information about CA-125 response by regimen and, where possible, by objective tumor response.

OUTLINE: This is a multicenter study. Patients are stratified according to their platinum-free interval (≤ 182 days vs > 182 days), measurable disease status (measurable vs non-measurable or "detectable" disease), and prior treatment with bevacizumab/aflibercept (no vs yes). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral everolimus once daily on days 1-28.
  • Arm II: Patients receive bevacizumab as in arm I and oral placebo once 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 treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal cancer

    • Recurrent or persistent disease
  • Meets 1 of the following criteria:

    • Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest dimension to be recorded) as ≥ 20 mm by chest x-ray OR as ≥ 10 mm by spiral CT scan, MRI, or caliper measurement by clinical exam

      • Must have ≥ 1 "target lesion" that can be used to assess response to study treatment as defined by RECIST criteria

        • 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 ≥ 90 days following completion of radiotherapy
      • Lymph nodes must be ≥ 15 mm in short axis by CT scan or MRI
    • Detectable disease, defined as non-measurable disease meeting ≥ 1 of the following criteria:

      • CA-125 ≥ 2 times upper limit of normal (ULN) at baseline
      • Ascites and/or pleural effusion attributed to tumor
      • Solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST criteria definitions for target lesions
  • Must have received 1 prior platinum-based chemotherapeutic regimen that contained carboplatin, cisplatin, or another organoplatinum compound for management of the primary disease

    • Initial treatment may have included intraperitoneal therapy, consolidation therapy, non-cytotoxic therapy, or extended therapy administered after surgical or non-surgical assessment
    • Prior biologic (non-cytotoxic) therapy as part of the primary treatment regimen allowed

      • No prior non-cytotoxic therapy for management of recurrent or persistent disease
    • Two additional prior cytotoxic regimens for management of recurrent or persistent disease allowed (≤ 1 non-platinum, non-taxane regimen allowed)
    • Patients who have received only one prior cytotoxic regimen (i.e., platinum-based regimen for management of primary disease) must have a platinum-free interval of < 12 months OR have progressed during platinum-based therapy OR have persistent disease after platinum-based therapy
  • Not eligible for a higher priority GOG clinical trial (i.e., any active phase III GOG protocol or Rare Tumor protocol for the same patient population)
  • No history or evidence of CNS disease by physical exam, including primary brain tumor or brain metastases

PATIENT CHARACTERISTICS:

  • GOG performance status (PS) 0-2 (for patients who have had 1 prior treatment)
  • GOG PS 0-1 (for patients who have had 2 or 3 prior treatments)
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Creatinine ≤ 1.5 times ULN
  • Bilirubin ≤ 1.5 times ULN
  • SGOT ≤ 3.0 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN
  • PT/INR ≤ 1.5 (or an in-range INR, usually between 2 and 3, if the patient is on a stable dose of therapeutic warfarin for management of deep vein thrombosis, including pulmonary embolism)
  • PTT ≤ 1.5 times ULN
  • Fasting serum cholesterol ≤ 300 mg/dL (or ≤ 7.75 mmol/L) AND fasting triglycerides ≤ 300 mg/dL (or ≤ 3.42 mmol/L)
  • Urine protein:creatinine ratio < 1.0
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other invasive malignancies within the past 3 years except nonmelanoma skin cancer
  • No clinically significant cardiovascular disease, including any of the following:

    • Uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg
    • Myocardial infarction or unstable angina within the past 6 months
    • NYHA class II-IV congestive heart failure
    • Serious cardiac arrhythmia requiring medication (asymptomatic, atrial fibrillation with controlled ventricular rate allowed)
    • Ejection fraction < 50% in patients who received prior treatment with an anthracycline (including doxorubicin hydrochloride and/or liposomal doxorubicin hydrochloride)
    • Peripheral vascular disease ≥ CTCAE grade 2 (i.e., at least brief [< 24 hours] episodes of ischemia managed non-surgically and without permanent deficit)
    • Cerebrovascular accident or transient ischemic attack within the past 6 months
  • No acute hepatitis or active infection requiring parenteral antibiotics (except for uncomplicated urinary tract infection)
  • No history or evidence of seizures not controlled with standard medical therapy
  • No subarachnoid hemorrhage within the past 6 months
  • No active bleeding or pathologic condition that carries a high risk of bleeding (e.g., known bleeding disorder, coagulopathy, or tumor involving major vessels)
  • No abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within the past 28 days
  • No clinical symptoms or signs of GI obstruction or requirement for parenteral hydration and/or nutrition
  • No serious non-healing wound, ulcer, or bone fracture
  • No known hypersensitivity to murine or chimeric antibodies
  • No other medical history or condition that, in the opinion of the investigator, would preclude study participation

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from prior surgery, radiotherapy, or chemotherapy
  • No prior everolimus or any other mTOR inhibitor
  • No prior cancer treatment that would contraindicate study therapy
  • No prior radiotherapy to any portion of the abdominal cavity or pelvis other than for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the past 5 years

    • Prior radiotherapy for localized cancer of the breast, head and neck, or skin allowed provided it was completed > 3 years ago 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 past 5 years

    • Prior adjuvant chemotherapy for localized breast cancer allowed provided it was completed > 3 years ago and the patient remains free of recurrent or metastatic disease
  • For the purposes of this study, poly (ADP-ribose) polymerase (PARP) inhibitors will be considered "cytotoxic," and prior treatment with PARP inhibitors for primary or recurrent disease WILL be allowed (either alone or in combination with chemotherapy)
  • At least 12 weeks since prior chimeric, human, or humanized monoclonal antibodies (including bevacizumab) or VEGF receptor fusion protein (including aflibercept)
  • More than 30 days since prior and no other concurrent investigational therapy
  • More than 28 days since prior major surgery
  • At least 3 weeks since any other prior therapy directed at the malignant tumor, including biological or immunologic agents (small molecules or murine monoclonal antibodies)
  • At least 1 week since prior hormonal therapy directed at the malignant tumor
  • No other concurrent anticancer agents
  • No concurrent chronic treatment with systemic steroids or other immunosuppressive agents
  • Concurrent warfarin allowed for prophylaxis or treatment of thrombosis
  • Concurrent low molecular weight heparin allowed provided PT/INR is ≤ 1.5
  • Concurrent low-dose aspirin (≤ 325 mg/day) allowed for patients at a higher risk for arterial thromboembolic disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00886691

  Show 45 Study Locations
Sponsors and Collaborators
Gynecologic Oncology Group
Genentech, Inc.
Novartis Pharmaceuticals
Investigators
Study Chair: William P. Tew, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Gynecologic Oncology Group
ClinicalTrials.gov Identifier: NCT00886691     History of Changes
Other Study ID Numbers: GOG-0186G, NCI-2011-01914
Study First Received: April 22, 2009
Last Updated: May 28, 2013
Health Authority: United States: Food and Drug Administration
United States: National Cancer Institute

Keywords provided by Gynecologic Oncology Group:
recurrent ovarian epithelial cancer
recurrent fallopian tube cancer
recurrent primary peritoneal cavity cancer

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Ovarian Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Peritoneal Diseases
Urogenital Neoplasms
Bevacizumab
Everolimus
Sirolimus
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances

ClinicalTrials.gov processed this record on November 20, 2014