Clinical trial NCT00025233: Bevacizumab in Treating Patients With Persistent or Recurrent Cancer of the Cervix
Official title: A Phase II Trial of Bevacizumab (rhuMAB VEGF) (NSC #704865) in the Treatment of Persistent and Recurrent Squamous Cell Carcinoma of the Cervix (Group A)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cervical Squamous Cell Carcinoma
Recurrent Cervical Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Gynecologic Oncology Group
First posted: 2003-01-27
Enrollment: 50
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 cancer of the cervix. 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: OBJECTIVES:

I. Determine the cytostatic antitumor activity of bevacizumab, in terms of 6-month progression-free survival (PFS), in patients with persistent or recurrent squamous cell carcinoma of the cervix.

II. Determine the nature and degree of toxicity of this drug in these patients. III. Estimate the distribution of PFS and overall survival for patients treated with this drug.

IV. Determine the frequency of clinical response (partial and complete) in patients treated with this drug.

V. Determine the role of age and initial performance status as prognostic factors in patients treated with this drug.

VI. Determine whether biological and imaging markers are associated with clinical efficacy of this drug, such as 6-month PFS, in these patients.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 3 weeks 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.

PROJECTED ACCRUAL: A total of 19-51 patients will be accrued for this study within 11-38 months.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed persistent or recurrent squamous cell carcinoma (SCC) of the cervix
* Patients must have received at least 1, but no more than 2, prior cytotoxic chemotherapy regimens for advanced, metastatic, or recurrent SCC of the cervix

  * Chemotherapy administered as a radio-sensitizer does not count as 1 regimen
* Documented disease progression
* At least 1 unidimensionally measurable lesion\*

  * At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
* No tumor involving major blood vessels
* No history or physical evidence of CNS disease, including primary or metastatic brain tumor
* Ineligible for a higher priority Gynecological Oncology Group (GOG) protocol (if one exists), including any active GOG phase III protocol for the same patient population
* Performance status - GOG 0-2 (if received 1 prior regimen)
* Performance status - GOG 0-1 (if received 2 prior regimens)
* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* No known bleeding disorder or coagulopathy
* No other active bleeding or pathologic condition that would confer a high risk of bleeding
* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* SGOT ≤ 2.5 times ULN
* Alkaline phosphatase ≤ 2.5 times ULN
* INR ≤ 1.5 (or 2-3 for patients on a stable dose of therapeutic warfarin or low molecular weight heparin)
* PTT \< 1.2 times control
* Creatinine ≤ 1.5 times ULN
* Creatinine clearance \> 60 mL/min
* No proteinuria

  * Urine protein \< 1+ on dipstick or \< 30 mg/dL
  * Urine protein \< 1000 mg by 24-hour urine collection
* No clinically significant cardiovascular disease
* No uncontrolled hypertension
* No myocardial infarction or unstable angina within the past 6 months
* No New York Heart Association grade II-IV congestive heart failure
* No serious cardiac arrhythmia requiring medication
* No grade II or greater peripheral vascular disease
* No history of stroke within the past 5 years
* No greater than grade 1 sensory or motor neuropathy
* No active infection requiring parenteral antibiotics
* No serious nonhealing wound, ulcer, or bone fracture
* No history or physical evidence of seizures not controlled with standard medical therapy
* No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
* No other invasive malignancy within the past 5 years except nonmelanomatous skin cancer
* No significant traumatic injury within the past 4 weeks
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for at least 3 months after completion of study treatment
* No prior bevacizumab
* At least 3 weeks since prior immunologic agents for SCC of the cervix
* See Disease Characteristics
* Recovered from prior chemotherapy
* No prior non-cytotoxic chemotherapy for persistent or recurrent disease
* At least 1 week since prior hormonal therapy for SCC of the cervix
* Concurrent hormone replacement therapy allowed
* See Disease Characteristics
* Recovered from prior radiotherapy
* Recovered from recent prior surgery
* At least 4 weeks since prior major surgical procedure or open biopsy
* At least 1 week since prior placement of vascular access device or core biopsy
* No concurrent major surgical procedure
* At least 3 weeks since other prior therapy for SCC of the cervix
* No prior anticancer therapy that would preclude study therapy
* No concurrent anticoagulants other than those required to maintain the patency of indwelling IV catheters
* No concurrent chronic daily aspirin greater than 325 mg/day or other nonsteroidal anti-inflammatory medications that are known to inhibit platelet function at doses used for chronic inflammatory diseases

Primary outcomes:
measure: Progression-free Survival Greater Than 6 Months
timeFrame: Every other 3-week treatment cycle for 6 months
measure: Maximum Severity of Each Adverse Event Per Patient, Graded According to Common Toxicity Criteria Version 2.0
timeFrame: Every cycle and 30 days after the end of treatment. (average 5 months)
Secondary outcomes:
measure: Tumor Response
timeFrame: Every other cycle during treatment and at the time of treatment discontinuation. (average 5 months)
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 during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years
measure: Performance Status
timeFrame: Baseline
measure: Age at Enrollment
timeFrame: Baseline
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Gynecologic Oncology Group
state: Pennsylvania
Study officials:
affiliation: Gynecologic Oncology Group
name: Bradley Monk
role: PRINCIPAL_INVESTIGATOR
References: