Bevacizumab and Intravenous or Intraperitoneal Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00951496
First received: August 1, 2009
Last updated: July 28, 2014
Last verified: June 2014
  Purpose

This randomized phase III trial is studying bevacizumab and intravenous chemotherapy to see how well they work compared with bevacizumab and intraperitoneal chemotherapy in treating patients with stage II, stage III, or stage IV ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer. 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. Drugs used in chemotherapy, such as paclitaxel, carboplatin, and cisplatin, 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 giving bevacizumab together with intravenous chemotherapy is more effective than giving bevacizumab together with intraperitoneal chemotherapy in treating patients with ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.


Condition Intervention Phase
Brenner Tumor
Ovarian Clear Cell Cystadenocarcinoma
Ovarian Endometrioid Adenocarcinoma
Ovarian Mixed Epithelial Carcinoma
Ovarian Mucinous Cystadenocarcinoma
Ovarian Serous Cystadenocarcinoma
Ovarian Undifferentiated Adenocarcinoma
Stage IIA Fallopian Tube Cancer
Stage IIA Ovarian Epithelial Cancer
Stage IIA Primary Peritoneal Cavity Cancer
Stage IIB Fallopian Tube Cancer
Stage IIB Ovarian Epithelial Cancer
Stage IIB Primary Peritoneal Cavity Cancer
Stage IIC Fallopian Tube Cancer
Stage IIC Ovarian Epithelial Cancer
Stage IIC Primary Peritoneal Cavity Cancer
Stage IIIA Fallopian Tube Cancer
Stage IIIA Ovarian Epithelial Cancer
Stage IIIA Primary Peritoneal Cavity Cancer
Stage IIIB Fallopian Tube Cancer
Stage IIIB Ovarian Epithelial Cancer
Stage IIIB Primary Peritoneal Cavity Cancer
Stage IIIC Fallopian Tube Cancer
Stage IIIC Ovarian Epithelial Cancer
Stage IIIC Primary Peritoneal Cavity Cancer
Stage IV Fallopian Tube Cancer
Stage IV Ovarian Epithelial Cancer
Stage IV Primary Peritoneal Cavity Cancer
Drug: paclitaxel
Drug: carboplatin
Biological: bevacizumab
Drug: cisplatin
Other: quality-of-life assessment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Clinical Trial of Bevacizumab With IV Versus IP Chemotherapy in Ovarian, Fallopian Tube, and Primary Peritoneal Carcinoma NCI-Supplied Agent(s): Bevacizumab (NSC #704865)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: From date that each patient is enrolled onto the study to the date of the patient's first failure event, assessed up to 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Frequency and severity of adverse events, as defined by NCI CTCAE version 3.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
    Safety endpoints will be summarized with descriptive statistics for the patients in the safety analysis dataset.

  • Quality of life and other patient-reported outcomes (e.g., neuropathy, abdominal discomfort, fatigue, and nausea) as assessed by FACT-O-TOI, FACT-GOG/NTX4, FACT-GOG/AD, FACIT-Fatigue, and FACT-Nausea questionnaires [ Time Frame: Up to week 84 ] [ Designated as safety issue: No ]

Estimated Enrollment: 1500
Study Start Date: July 2009
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (paclitaxel, carboplatin, bevacizumab)
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Patients also receive bevacizumab IV over 30-90 minutes on day 1 in courses 2-6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab alone in courses 7-22 in the absence of disease progression or unacceptable toxicity.
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm II (paclitaxel, bevacizumab, carboplatin IP)
Patients receive paclitaxel as in arm I and carboplatin IP on day 1. Patients also receive bevacizumab as in arm I. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab alone as in arm I.
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: carboplatin
Given IP
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm III (paclitaxel IP, bevacizumab, cisplatin IP)
Patients receive paclitaxel IV over 3 hours on day 1, cisplatin IP on day 2, and paclitaxel IP on day 8. Patients also receive bevacizumab as in arm I. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab alone as in arm I.
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: cisplatin
Given IP
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: paclitaxel
Given IP
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal carcinoma, including any of the following epithelial cell types*:

    • Serous adenocarcinoma
    • Endometrioid adenocarcinoma
    • Mucinous**adenocarcinoma
    • Undifferentiated carcinoma
    • Clear** cell adenocarcinoma
    • Mixed epithelial carcinoma
    • Transitional cell carcinoma
    • Malignant Brenner tumor
    • Adenocarcinoma not otherwise specified
  • Stage II, III, or IV disease with either optimal (≤ 1 cm residual disease) or suboptimal residual disease
  • Must have undergone surgery for diagnosis, staging, and/or cytoreduction within the past 12 weeks
  • Prior or concurrent primary endometrial cancer allowed provided the primary origin of the invasive tumor is ovarian or peritoneal and all of the following criteria are met:

    • Stage of endometrial cancer is ≤ IB
    • No more than superficial myometrial invasion, without vascular or lymphatic invasion
    • No poorly differentiated subtypes, including papillary serous, clear cell, or other FIGO grade 3 lesions
  • No borderline ovarian epithelial tumor ("tumors of low malignant potential") (e.g., stage IA or IB disease with low-grade lesions)

    • Patients with a prior diagnosis of a borderline tumor that was surgically resected and who subsequently develop an unrelated, new invasive ovarian epithelial or primary peritoneal cancer are eligible provided they have not received prior chemotherapy for any ovarian tumor
  • No recurrent invasive ovarian epithelial cancer treated with surgery only
  • No history or evidence of major CNS disease by physical examination (e.g., primary brain tumor, metastatic cancer in the brain, seizures not controlled with standard medical therapy, or any brain metastases within the past 6 months
  • No metastatic tumor in the parenchyma of the liver or lungs with proximity to large vessels
  • GOG performance status 0-2
  • ANC ≥ 1,500/mm³ (without granulocyte colony-stimulating factor support)
  • Platelet count ≥ 100,000/mm³
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN
  • Creatinine normal
  • Urine protein:creatinine ratio < 1.0
  • PTT <1.5 times ULN

    • Concurrent heparin, lovenox or alternative anticoagulants allowed
  • PT/INR ≤ 1.5 times ULN (or an in-range INR, usually between 2 and 3, if patient is on a stable dose of therapeutic warfarin)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
  • No sensory or motor neuropathy > CTCAE grade 1
  • No seizures not controlled with standard medical therapy
  • No other invasive malignancies within the past 5 years, except nonmelanoma skin cancer
  • No acute hepatitis or active infection requiring parenteral antibiotics
  • No serious non-healing wound, ulcer, or bone fracture

    • Granulating incisions healing by secondary intention allowed provided there is no evidence of fascial dehiscence or infection AND the wound is examined weekly during study
  • No clinical symptoms or signs of gastrointestinal obstruction and/or those who require parenteral hydration and/or nutrition

    • Patients with a history or current diagnosis of inflammatory bowel disease are not eligible
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • 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 cerebrovascular accident (stroke), transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
  • No clinically significant cardiovascular disease, including any of the following:

    • Uncontrolled hypertension, defined as systolic BP > 150 mmHg or diastolic BP > 90 mmHg
    • 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 or history of supraventricular tachycardia controlled with medications and asymptomatic allowed
    • Peripheral vascular disease ≥ CTCAE grade 2 (at least brief [< 24 hrs] episodes of ischemia managed non-surgically and without permanent deficit)
  • No history or evidence of cerebrovascular accident (CVA, stroke), transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
  • No known allergy to Cremophor or polysorbate 80
  • No significant traumatic injury within the past 28 days
  • No other medical history or condition (e.g., persistent gastrointestinal symptoms resulting from clostridia difficile enterocolitis or bowl surgery; or hearing loss or neuropathy) that, in the opinion of the investigator, would preclude study participation
  • Concurrent ovarian estrogen (with or without progestin) replacement therapy for control of menopausal symptoms allowed provided the lowest effective dose(s) is (are) given

    • No concurrent high-dose of progestins as an appetite stimulant
  • No prior radiotherapy to any portion of the abdominal cavity or pelvis

    • Prior radiotherapy for localized cancer of the breast, head and neck, or skin allowed provided it was completed > 3 years ago AND patient remains free of recurrent or metastatic disease
  • No prior chemotherapy for any abdominal or pelvic tumor, including neoadjuvant chemotherapy for ovarian or primary peritoneal cancer

    • Prior adjuvant chemotherapy for localized breast cancer allowed provided it was completed > 3 years ago AND patient remains free of recurrent or metastatic disease
  • No prior targeted therapy (including vaccines, antibodies, or tyrosine kinase inhibitors) or hormonal therapy for management of ovarian epithelial or primary peritoneal cancer
  • No prior anti-VEGF therapy, including bevacizumab
  • No prior cancer treatment that would contraindicate study treatment
  • More than 7 days since prior core biopsy
  • More than 28 days since prior major surgical procedure or open biopsy
  • No concurrent major surgical procedure, including, but not limited to, abdominal surgery (laparotomy or laparoscopy) before disease progression (e.g., colostomy or enterostomy reversal, secondary cytoreductive surgery, or second-look surgery)
  • No other concurrent anti-neoplastic therapy, including cytotoxic therapy, biologic therapy, hormonal therapy, or radiotherapy
  • No concurrent amifostine or other protective reagents
  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: NCT00951496

  Show 499 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Joan Walker Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00951496     History of Changes
Other Study ID Numbers: NCI-2011-01956, NCI-2011-01956, CDR0000650601, GOG-0252, GOG-0252, U10CA027469
Study First Received: August 1, 2009
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Brenner Tumor
Carcinoma
Cystadenocarcinoma
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Carcinoma, Endometrioid
Cystadenocarcinoma, Mucinous
Cystadenocarcinoma, Serous
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Fibroepithelial
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Gonadal Disorders
Endocrine System Diseases
Neoplasms, Cystic, Mucinous, and Serous
Abdominal Neoplasms
Neoplasms by Site
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases

ClinicalTrials.gov processed this record on July 28, 2014