Bevacizumab and Low-Dose Cyclophosphamide in Treating Patients With Recurrent Ovarian Epithelial or Primary Peritoneal Cancer

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Primary Peritoneal Carcinoma

Recurrent Ovarian Carcinoma

Stage IV Ovarian Cancer

Treatments

Drug: Cyclophosphamide

Other: Laboratory Biomarker Analysis

Biological: Bevacizumab

Study type

Interventional

Funder types

NIH

Identifiers

NCT00072566

CDR0000340522

N01CM17101 (U.S. NIH Grant/Contract)

P30CA033572 (U.S. NIH Grant/Contract)

NCI-5789

CCC-PHII-45

CHNMC-PHII-45

NCI-2012-02562 (Registry Identifier)

PHII-45 (Other Identifier)

5789 (Other Identifier)

Details and patient eligibility

About

This phase II trial is to see if combining bevacizumab with low-dose cyclophosphamide works in treating patients with ovarian epithelial or primary peritoneal cancer that has come back or spread to other parts of the body. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining bevacizumab with cyclophosphamide may kill more tumor cells.

Full description

OBJECTIVES: Primary I. Determine the time to progression in patients with recurrent ovarian epithelial or primary peritoneal cancer treated with bevacizumab and low-dose cyclophosphamide.

Secondary I. Determine the response rate in patients treated with this regimen. II. Determine the toxicity of this regimen in these patients. III. Determine molecular correlates for response and outcomes in patients treated with this regimen.

OUTLINE: This is a nonrandomized, multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on days 1, 8, and 15 for the first course and on days 1 and 15 for all subsequent courses. Patients also receive low-dose oral cyclophosphamide on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 23-55 patients will be accrued for this study within 1-2 years.

Enrollment

70 patients

Sex

Female

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Histologically confirmed recurrent or metastatic ovarian epithelial or primary peritoneal cancer
Unidimensionally measurable disease
- Previously irradiated indicator lesions must have progressed after radiotherapy
Received a platinum-containing regimen for primary disease
No more than 2 prior chemotherapy regimens for recurrent disease
- Must have received prior platinum-based chemotherapy for recurrent disease if it has been > 12 months since treatment for primary disease (except if hypersensitivity to platinum has developed)
- Rechallenge with the same platinum-based regimen is considered 1 prior regimen
No history or clinical evidence of CNS disease, including primary brain tumor
No brain metastases
Performance status - SWOG 0-2
At least 3 months
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
No bleeding diathesis
No coagulopathy
Bilirubin no greater than 1.5 times normal
ALT or AST no greater than 3 times upper limit of normal
INR less than 1.5 (for patients receiving warfarin)
Creatinine no greater than 1.5 times normal
No proteinuria (less than 1+)
Proteinuria less than 500 mg/24-hour urine collection
No prior deep vein thrombosis
No prior stroke
No clinically significant cardiovascular disease
None of the following within the past year:
- Uncontrolled hypertension
- New York Heart Association class II-IV congestive heart failure
- Serious cardiac arrhythmia requiring medication
- Grade II or greater peripheral vascular disease
None of the following within the past 6 months:
- Unstable angina
- Myocardial infarction
- Transient ischemic attack
- Cerebrovascular accident
- Other arterial thromboembolic event
No clinically significant peripheral artery disease
No active infection requiring parenteral antibiotics
No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
Not pregnant or nursing
Fertile patients must use effective contraception
No serious, non-healing wound, ulcer, or bone fracture
No significant traumatic injury within the past 28 days
No seizures not controlled with standard medical therapy
No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
- All prior invasive malignancies must be in complete remission
No other concurrent medical, psychological, or social condition that would preclude study participation
No prior antiangiogenesis agents
See Disease Characteristics
Recovered from prior chemotherapy
See Disease Characteristics
Recovered from prior radiotherapy
More than 28 days since prior major surgical procedure or open biopsy and recovered
At least 3 weeks since prior therapy directed at the malignancy
No recent or concurrent full-dose anticoagulants or thrombolytic agents
- Anticoagulants to maintain patency of preexisting, permanent indwelling IV catheters allowed
No concurrent chronic daily aspirin (greater than 325 mg/day) or nonsteroidal anti-inflammatory drugs known to inhibit platelet function