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A Phase II Study of Bevacizumab in Combination With Definitive Radiotherapy and Cisplatin Chemotherapy in Untreated Patients With Locally Advanced Cervical Carcinoma

Phase 2
Open (Enrolling)
Cervical Adenocarcinoma, Cervical Adenosquamous Cell Carcinoma, Cervical Squamous Cell Carcinoma, Stage IB Cervical Cancer, Stage IIA Cervical Cancer, Stage IIB Cervical Cancer, Stage III Cervical Cancer

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Trial Information

A Phase II Study of Bevacizumab in Combination With Definitive Radiotherapy and Cisplatin Chemotherapy in Untreated Patients With Locally Advanced Cervical Carcinoma


I. Determine treatment-related serious adverse-event rates and adverse-event rates within
the first 90 days from treatment start in patients with previously untreated locally
advanced carcinoma of the cervix treated with bevacizumab, cisplatin, and concurrent pelvic


I. Evaluate treatment-related serious adverse events and adverse events at any time.

II. Evaluate disease-free survival (local, regional, or distant failure, or death due to any

III. Evaluate overall survival (death due to any cause).

IV. To collect tissue to perform future immunohistochemical analyses for angiogenic markers
to correlate with clinical outcome; to collect tissue to perform future microarray testing
for evaluation of gene expression.

V. To collect urine and serum for future cytokine analysis.

VI. To implement the image-based brachytherapy guidelines proposed by the Transatlantic
Image-guided Brachytherapy Working Group and collect CT or MRI-based dosimetry of
brachytherapy applications used during the course of treatment for later analysis of
feasibility and consistency as well as dose/volume assessments of tumor control and

OUTLINE: This is a multicenter study.

Patients undergo pelvic external-beam radiotherapy (EBRT) once daily, 5 days a week, for 5
weeks for a total of 45 Gy.

Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning >=
4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, >= 48 hours apart,
beginning >= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of
high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1,
15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35.

After completion of study treatment, patients are followed periodically.

Inclusion Criteria:

- Histologically confirmed squamous cell, adenocarcinoma, or adenosquamous cell
carcinoma of the uterine cervix, meeting 1 of the following stage criteria:

- Stage IIB-IIIB

- Stage IB-IIA disease with biopsy-proven pelvic node metastases and/or tumor size
>= 5 cm

- No positive para-aortic lymph nodes

- Zubrod performance status 0-2

- WBC >= 3,000/mm^3

- Absolute granulocyte count >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- INR < 1.5

- Total bilirubin =< 1.5 mg/dL

- Serum creatinine =< 1.5 mg/dL

- AST and ALT =< 2.5 times upper limit of normal (ULN)

- Serum calcium =< 1.3 times ULN

- Hemoglobin >= 10 g/dL (transfusion allowed)

- Urine protein:creatinine ratio ≤ 0.5 OR urine protein < 1,000 mg by 24-hour urine

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- None of the following illnesses or conditions:

- Medical illness preventing the use of full-dose chemotherapy

- Evidence of bleeding diathesis or coagulopathy

- Prior medical or psychiatric illness that would prevent informed consent or
limit survival to < 6 months

- History of aneurysms, cerebrovascular accident, or arteriovenous malformations

- Active gastrointestinal (GI) ulcers, GI bleeding, or active inflammatory bowel

- Serious, nonhealing wound, ulcer, or current healing fracture

- History of any type of fistula or GI perforation

- Intra-abdominal abscess within the past 6 months

- No prior invasive malignancy (except nonmelanomatous skin cancer) unless disease free
for >= 3 years

- No significant traumatic injury within the past 28 days

- No clinically significant cardiovascular disease, such as the following:

- Uncontrolled hypertension (blood pressure > 160/90 mm Hg on medication)

- Myocardial infarction within the past 12 months

- Unstable angina within the past 12 months

- New York Heart Association class II-IV congestive heart failure

- Unstable symptomatic arrhythmia requiring medication (i.e., chronic atrial
arrhythmia, atrial fibrillation, or paroxysmal supraventricular tachycardia)

- Arterial thromboembolic events, including transient ischemic attack or
clinically significant peripheral artery disease, within the past 6 months

- Arterial thromboembolic events, including transient ischemic attack or clinically
significant peripheral artery disease, within the past 6 months

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

- No known HIV

- No prior organ transplant

- No prior surgery for carcinoma of the cervix other than biopsy

- No prior surgical debulking of pelvic or para-aortic nodes

- No prior pelvic radiotherapy, including transvaginal irradiation to control bleeding

- No prior systemic chemotherapy

- No major surgical procedure or open biopsy within the past 28 days or anticipation of
need for major surgical procedure during the course of the study

- No fine needle aspirations or core biopsies within the past 7 days

- No concurrent major surgical procedure

- No concurrent epoetin alfa or Hypericum perforatum (St. John's wort)

- No concurrent intensity-modulated radiotherapy

- No concurrent transvaginal irradiation to control bleeding

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Subjects With Treatment-related Serious Adverse Events (SAEs) and Adverse Events (AEs) as Assessed by CTCAE v. 3.0 Criteria Within the First 90 Days From Treatment Start.

Outcome Description:

Treatment-related SAEs defined as Grade (Gr) >= 4 vaginal bleeding, Gr >=4 thrombotic event, Gr >=3 arterial event, gastrointestinal (GI) bleeding , or bowel/bladder perforation, and any Gr 5 treatment-related AE. Treatment-related AEs defined as all SAEs, Gr 3-4 nausea, vomiting, or diarrhea persisting for >2 weeks depsite medical intervention, Gr 4 neutropenia or leukopenia persisiting for >7 days, febrile neutropenia defined as a temperature >38.5 degree Celsius and granulocytes < 1000/mm3, Grade 3-4 hematologic toxicity with the exception of neutropenia and leukopenia, and Grade 3-4 GI, renal, cardiac, pulmonary, hepatic, or neurologic AEs. Based on a report by Laciano, et al. an SAE rate of 5% and AE rate of 35% were considered tolerable and an SAE rate >=20% and AE rate >=55% excessive. If there were >=6 pts with SAES or >=22 pts with AEs then the treatment would be rejected. This study design provides alpha of 0.05 and power of 90%.

Outcome Time Frame:

From start of treatment to 90 days.

Safety Issue:


Principal Investigator

Tracey Schefter

Investigator Role:

Principal Investigator

Investigator Affiliation:

American College of Radiology Imaging Network


United States: Food and Drug Administration

Study ID:




Start Date:

August 2006

Completion Date:

Related Keywords:

  • Cervical Adenocarcinoma
  • Cervical Adenosquamous Cell Carcinoma
  • Cervical Squamous Cell Carcinoma
  • Stage IB Cervical Cancer
  • Stage IIA Cervical Cancer
  • Stage IIB Cervical Cancer
  • Stage III Cervical Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Uterine Cervical Neoplasms
  • Carcinoma, Adenosquamous



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