Clinical trial NCT00301964: Bevacizumab in Treating Patients With Recurrent or Persistent Endometrial Cancer
Official title: A Phase II Evaluation of Bevacizumab (NCI-Supplied Agent: NSC# 704865, IND # 7921) in the Treatment of Recurrent or Persistent Endometrial Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Endometrial Carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Gynecologic Oncology Group
First posted: 2006-03-13
Enrollment: 56
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 studying how well bevacizumab works in treating patients with recurrent or persistent endometrial cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor.

Detailed description: PRIMARY OBJECTIVES:

I. Assess the activity of bevacizumab, in terms of 6-month progression-free survival rate and objective tumor response, in patients with recurrent or persistent endometrial cancer.

II. Determine the nature and degree of toxicity of bevacizumab in these patients.

SECONDARY OBJECTIVES:

I. Determine the duration of progression-free survival and overall survival of these patients.

II. Determine the effects of prognostic factors, including performance status and histological grade.

OUTLINE:

Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Eligibility criteria: Inclusion Criteria:

* Recurrent or persistent endometrial carcinoma with histologic confirmation of the original primary tumor

  * Refractory to curative therapy or established treatments
* Measurable disease

  * At least one non previously irradiated lesion that can be accurately measured in ≥ 1 dimension as ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

    * Previously irradiated lesion allowed provided disease progression is documented or a biopsy obtained to confirm persistent disease ≥ 90 days after completion of prior radiotherapy
* Must have received 1 prior chemotherapy regimen for endometrial carcinoma

  * May include high-dose therapy, consolidation, or extended therapy after surgical or nonsurgical assessment
* Not eligible for a higher priority GOG protocol, if one exists
* No tumor involving major vessels
* No prior history or evidence of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, or any brain metastases
* GOG performance status (PS) 0-2 (if received 1 prior treatment regimen)
* GOG PS 0-1 (if received 2 prior treatment regimens)
* Absolute neutrophil count ≥ 1,000/mm³
* Platelet count ≥ 100,000/mm³
* Creatinine ≤ 1.5 times upper limit of normal (ULN)
* Serum bilirubin ≤ 1.5 times ULN
* SGOT and alkaline phosphatase ≤ 2.5 times ULN
* Urine protein:creatinine ratio \< 1.0
* INR \< 1.5 (or in-range, usually between 2 and 3, if the patient is on a stable dose of therapeutic warfarin)
* PTT \< 1.5 times ULN
* No active infection requiring antibiotics
* No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
* No serious nonhealing wound or ulcer, including any of the following:

  * History of abdominal fistula
  * Gastrointestinal perforation
  * Intra-abdominal abscess within the past 28 days
* No serious nonhealing bone fracture
* No active bleeding or pathologic conditions that carry high risk of bleeding, including known bleeding disorder or coagulopathy
* No clinically significant cardiovascular disease, including any of the following:

  * Uncontrolled hypertension, defined as systolic blood pressure (BP) \> 150 mm Hg or diastolic BP \> 90 mm Hg
  * Myocardial infarction or unstable angina within the past 6 months
  * New York Heart Association class II-IV congestive heart failure
  * Serious cardiac arrhythmia requiring medication
  * Ejection fraction \< 50% and received prior anthracycline (including doxorubicin and/or doxorubicin HCl liposomal)
  * Grade 2 or greater peripheral vascular disease
  * History of cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
* No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
* No significant traumatic injury within the past 28 days
* See Disease Characteristics
* Recovered from recent surgery, radiotherapy, or chemotherapy
* Hormonal therapy directed at the malignant tumor must be discontinued ≥ 1 week prior to registration
* Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued ≥ 3 weeks prior to registration
* No prior chemotherapy or radiotherapy to any portion of the abdominal cavity or pelvis

  * Prior chemotherapy or radiotherapy for localized cancer of the breast, head and neck, or skin for which the patient remains free of recurrent or metastatic disease is allowed provided it was completed ≥ 3 years prior to study
* No prior cancer treatment that contraindicates study therapy
* No prior bevacizumab or other vascular endothelial growth factor (VEGF) pathway-targeted therapy
* One additional prior cytotoxic regimen for recurrent or persistent endometrial cancer allowed, including any agent that targets the genetic and/or mitotic apparatus of dividing cells resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa
* No prior noncytotoxic chemotherapy for recurrent or persistent disease
* More than 28 days since major surgical procedure or open biopsy
* More than 7 days since minor surgical procedures, fine needle aspirates, or core biopsies
* No concurrent major surgical procedure
* No concurrent prophylactic filgrastim (G-CSF) or thrombopoietic agents
* No concurrent amifostine or other protective reagents

Primary outcomes:
measure: Progression-free Survival Greater Than 6 Months
timeFrame: 6 months
measure: Best Tumor Response
timeFrame: study entry through completion
measure: Number of Patients With Toxicity of Bevacizumab as Assessed by CTCAE v3.0 in This Cohort of Patients.
timeFrame: Up to 5 years
Secondary outcomes:
measure: Progression-free Survival
timeFrame: Every other cycle for the first 6 months; then every 4 cycles until progression or death, up to 5 years.
measure: Overall Survival
timeFrame: Every 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: Initial Performance Status
timeFrame: Baseline
measure: Histologic Grade
timeFrame: Baseline
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Gynecologic Oncology Group
state: Pennsylvania
Study officials:
affiliation: Gynecologic Oncology Group
name: Carol Aghajanian
role: PRINCIPAL_INVESTIGATOR
References: