|Phase III||Biomarker/Laboratory analysis, Treatment||Closed||18 and over||NCI||NCI-2011-01956|
CDR0000650601, GOG-0252, U10CA027469, NCT00951496
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.
Further Study Information
I. To determine if one or both of the proposed intraperitoneal chemotherapy regimens improves the progression-free survival (PFS) event rate compared to standard intravenous chemotherapy for first-line treatment of patients diagnosed with advanced stage ovarian, peritoneal or fallopian tube cancer.
II. If both IP regimens significantly improve the PFS event rate compared to the standard regimen, then a second study objective is to determine whether IP cisplatin and IV paclitaxel on day one plus IP paclitaxel on day eight improves the PFS event rate when compared to the IP carboplatin and IV paclitaxel.
I. To determine if intraperitoneal chemotherapy reduces the overall death rate compared to standard intravenous chemotherapy.
II. To assess the frequency and severity of adverse events as defined by CTCAE version 3.0.
III. To compare the patient-reported outcomes on: Quality of Life (FACT-O-TOI), Neuropathy (FACT-GOG/NTX4 scale), Abdominal discomfort (FACT-GOG/AD scale), Fatigue (FACIT-Fatigue scale), and Nausea (item from FACT-O-TOI).
IV. To assess the frequency and the reasons for early discontinuation of the study treatments.
I. To bank DNA from whole blood for research and examine the association between single nucleotide polymorphisms (SNPs) and measures of clinical outcome including overall survival, progression-free survival and adverse events.
II. To bank archival tumor for research and examine the association between tumor markers and measures of clinical outcome including overall survival, progression-free survival and adverse events.
III. Patients will be encouraged to enroll on the companion translational research protocol (CEM0703 under development).
OUTLINE: This is a multicenter study. Patients are stratified according to disease stage (FIGO stage II vs stage III vs stage IV) and size of residual disease after initial staging/debulking surgery (no gross residual disease vs gross residual disease with lesion ≤ 1 cm vs any gross residual disease with lesion > 1 cm). Patients are randomized to 1 of 3 treatment arms.
ARM I: 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.
ARM II: Patients receive paclitaxel as in arm I and carboplatin intraperitoneally (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.
ARM III: 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.
Patients complete quality-of-life questionnaires at baseline and at weeks 9, 18, 36, 60, and 84. Blood and tissue samples may be collected for further laboratory analysis.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.
- Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal carcinoma, including any of the following epithelial cell types*:
- Serous adenocarcinoma
- Endometrioid 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
Trial Lead Organizations/Sponsors
National Cancer Institute
|Joan Walker||Principal Investigator|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00951496
ClinicalTrials.gov processed this data on October 17, 2013
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