Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	Not specified	NCI	CCC-PHII-45 CHNMC-PHII-45, NCI-5789, NCT00072566, 5789

Objectives

Primary

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

Secondary

1. Determine the response rate in patients treated with this regimen.
2. Determine the toxicity of this regimen in these patients.
3. Determine molecular correlates for response and outcomes in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

• No prior antiangiogenesis agents

Chemotherapy

• See Disease Characteristics
• Recovered from prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• Recovered from prior radiotherapy

Surgery

• More than 28 days since prior major surgical procedure or open biopsy and recovered

Other

• 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

Patient Characteristics:

Age

• Not specified

Performance status

• SWOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• No bleeding diathesis
• No coagulopathy

Hepatic

• 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)

Renal

• Creatinine no greater than 1.5 times normal
• No proteinuria (less than 1+)

  OR

• Proteinuria less than 500 mg/24-hour urine collection

Cardiovascular

• 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

Immunologic

• No active infection requiring parenteral antibiotics
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies

Other

• 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

Expected Enrollment

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

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.

Garcia AA, Hirte H, Fleming G, et al.: Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. J Clin Oncol 26 (1): 76-82, 2008.[PUBMED Abstract]

Schultheis AM, Yang D, Garcia AA, et al.: Angiogenesis pathway gene polymorphisms associated with clinical outcome in recurrent ovarian cancer treated with low dose cyclophosphamide and bevacizumab: a California Consortium Trial. [Abstract] J Clin Oncol 24 (Suppl 18): A-5017, 260s, 2006.

Trial Contact Information

Trial Lead Organizations

California Cancer Consortium

Agustin Garcia, MD, Study coordinator(Contact information may not be current)		Ph: 310-600-8400 Email: agarcia@premiereoncology.com

Registry Information
Official Title		Phase II Clinical Trial Of Bevacizumab (IND 7,921; NSC 704865) And Low Dose Oral Cyclophosphamide In Recurrent Ovarian Cancer Or Primary Peritoneal Carcinoma
Trial Start Date		2003-12-31
Registered in ClinicalTrials.gov		NCT00072566
Date Submitted to PDQ		2003-10-09
Information Last Verified		2005-05-04
NCI Grant/Contract Number		P30-CA33572, N01-CM17101