Clinical trial NCT00022659: Bevacizumab in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer or Primary Peritoneal Cancer
Official title: A Phase II Evaluation of Bevacizumab (Anti-VEGF Humanized Monoclonal Antibody) (NSC #704865) in the Treatment of Persistent or Recurrent Epithelial Ovarian or Primary Peritoneal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Peritoneal Cavity Cancer
Recurrent Ovarian Epithelial Cancer
Stage IV Ovarian Epithelial Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Gynecologic Oncology Group
First posted: 2003-01-27
Enrollment: 64
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial is to see if bevacizumab works in treating patients who have persistent or recurrent ovarian epithelial cancer 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.

Detailed description: PRIMARY OBJECTIVES:

I. Determine the 6-month progression-free survival of patients with persistent or recurrent ovarian epithelial or primary peritoneal cancer treated with bevacizumab.

II. Determine the nature and degree of toxicity of this drug in these patients. III. Determine the progression-free and overall survival of patients treated with this drug.

IV. Determine the frequency of clinical response in patients treated with this drug.

V. Determine the effect of this drug on initial performance status, age, and mucinous or clear cell histology in these patients.

VI. Correlate biological and imaging markers with 6-month progression-free survival of patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed ovarian epithelial or primary peritoneal carcinoma

  * Recurrent or persistent after initial standard surgery or chemotherapy
  * Incurable with standard surgery, chemotherapy, or radiotherapy
* At least 1 unidimensionally measurable target lesion

  * At least 20 mm by conventional techniques
  * At least 10 mm by spiral CT scan
  * Outside the area of prior radiotherapy
* Accessible to guided core needle biopsy
* Received 1 prior platinum-based chemotherapy regimen (e.g., carboplatin, cisplatin, or another organoplatinum compound) for primary disease

  * May have included high-dose therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment
  * Patients with only 1 prior platinum-based chemotherapy regimen must have an initial treatment-free interval of less than 12 months
  * Patients with an initial treatment-free interval of more than 12 months must have progressive disease after prior platinum-based chemotherapy regimen as second-line therapy
* No tumors involving major blood vessels
* No evidence of CNS disease (primary brain tumor or brain metastases) within the past 5 years
* Ineligible for higher priority Gynecologic Oncology Group (GOG) protocols (i.e., active phase III GOG protocols for the same patient population)
* Performance status - GOG 0-2 (patients who have received 1 prior regimen)
* Performance status - GOG 0-1 (patients who have received 2 prior regimens)
* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* No known bleeding disorder or coagulopathy
* No active bleeding
* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* serum glutamate oxaloacetate transaminase (SGOT) ≤ 2.5 times ULN
* Alkaline phosphatase ≤ 2.5 times ULN
* PT (INR) ≤ 1.5 (INR 2-3 if on stable dose of therapeutic warfarin or low molecular weight heparin)
* Partial thromboplastin time (PTT) \< 1.2 times control
* Creatinine ≤ 1.5 times ULN
* Creatinine clearance \> 60 mL/min
* No proteinuria, as indicated by 1 of the following:

  * Negative urine dipstick
  * Urine protein \< 30 mg/dL
  * Urine protein \< 1,000 mg on 24-hour urine collection
* No clinically significant cardiovascular disease, including any of the following:

  * Uncontrolled hypertension
  * Myocardial infarction within the past 6 months
  * Unstable angina within the past 6 months
  * New York Heart Association class II-IV congestive heart failure
  * Serious cardiac arrhythmia requiring medication
  * Peripheral vascular disease ≥ grade 2
* No stroke within the past 5 years
* No pathologic condition that carries a high risk of bleeding
* No significant traumatic injury within the past 28 days
* No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
* No uncontrolled seizures within the past 5 years
* No neuropathy (motor and sensory) ≥ grade 2
* No serious non-healing wound, ulcer, or bone fracture
* No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
* No active infection requiring parenteral antibiotics
* No known claustrophobia that would preclude MRI tolerance
* No ferromagnetic implants or pacers
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for at least 3 months after study treatment
* At least 3 weeks since prior immunologic therapy directed at malignancy
* No prior bevacizumab
* No other concurrent immunotherapy directed at malignancy
* One additional prior cytotoxic regimen for recurrent or persistent disease allowed
* No prior non-cytotoxic chemotherapy for recurrent or persistent disease
* No concurrent chemotherapy directed at malignancy
* At least 1 week since prior hormonal therapy directed at malignancy
* No concurrent hormonal therapy directed at malignancy
* Concurrent hormone replacement therapy allowed
* Recovered from prior radiotherapy
* No concurrent radiotherapy directed at malignancy
* At least 28 days since prior major surgery or open biopsy and recovered
* At least 7 days since prior core biopsy or placement of vascular access device
* No anticipated need for major surgical procedure during study participation
* At least 3 weeks since other prior therapy directed at malignancy
* No prior anticancer therapy that would preclude study entry

Primary outcomes:
measure: Progression-free Survival at 6 Months
timeFrame: Every other cycle for 6 months.
measure: Tumor Response
timeFrame: Every other cycle for the first 6 months; then every 3 months x 2 ; then every 6 months thereafter for up to 5 years.
measure: Number of Participants and Degree of Toxicity of Bevacizumab in This Cohort of Patients as Assessed by CTC.
timeFrame: Assessed every cycle while on treatment, 30 days after the last cycle of treatment, up to 5 years.
Secondary outcomes:
measure: Overall Survival
timeFrame: From study entry to death or last contact, up to 5 years.
measure: Duration of Progression-free Survival
timeFrame: Every other cycle for the first 6 months; then every 3 months x 2 ; then every 6 months therafter for up to 5 years.
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Gynecologic Oncology Group
state: Pennsylvania
Study officials:
affiliation: Gynecologic Oncology Group
name: Robert Burger
role: PRINCIPAL_INVESTIGATOR
References: