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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00072566
First received: November 4, 2003
Last updated: June 5, 2013
Last verified: June 2013
  Purpose

This phase II trial is to see if combining bevacizumab with low-dose cyclophosphamide works in treating patients who have recurrent or metastatic ovarian epithelial or primary peritoneal cancer. 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.


Condition Intervention Phase
Primary Peritoneal Cavity Cancer
Recurrent Ovarian Epithelial Cancer
Stage IV Ovarian Epithelial Cancer
Biological: bevacizumab
Drug: cyclophosphamide
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Clinical Trial Of Bevacizumab (IND 7,921; NSC 704865) And Low Dose Oral Cyclophosphamide In Recurrent Ovarian Cancer, Primary Peritoneal Carcinoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression free survival defined according to the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Kaplan-Meier plots will be constructed. Cox proportional hazards model will be used.


Secondary Outcome Measures:
  • Response rate based on the RECIST [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    A logistic regression model will be used.

  • Time to progression [ Time Frame: Time from first day of treatment to the first observation of disease progression, assessed up to 3 years ] [ Designated as safety issue: No ]
    Kaplan-Meier plots will be constructed.

  • Overall survival [ Time Frame: Time from first day of treatment to time of death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
    Kaplan-Meier plots will be constructed. Cox proportional hazards model will be used.

  • Toxicities based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    Tables will be created to summarize these toxicities and side effects by cycle and overall.


Enrollment: 55
Study Start Date: December 2003
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (bevacizumab, cyclophosphamide)
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.
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: cyclophosphamide
Given PO
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Other: laboratory biomarker analysis
Correlative studies

Detailed 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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  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: NCT00072566

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
Investigators
Principal Investigator: Agustin Garcia Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00072566     History of Changes
Other Study ID Numbers: NCI-2012-02562, PHII-45, NCI-5789, CDR0000340522, CHNMC-PHII-45, CCC-PHII-45, N01CM17102, N01CM17107, N01CM17101
Study First Received: November 4, 2003
Last Updated: June 5, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Digestive System Neoplasms
Endocrine Gland Neoplasms
Genital Neoplasms, Female
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Urogenital Neoplasms
Bevacizumab
Adnexal Diseases
Digestive System Diseases
Endocrine System Diseases
Genital Diseases, Female
Gonadal Disorders
Ovarian Diseases
Peritoneal Diseases
Antibodies
Antibodies, Monoclonal
Cyclophosphamide
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Growth Inhibitors
Growth Substances

ClinicalTrials.gov processed this record on October 30, 2014