Bevacizumab, Radiation Therapy, and Cisplatin in Treating Patients With Previously Untreated Locally Advanced Cervical Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00369122
First received: August 24, 2006
Last updated: September 22, 2014
Last verified: October 2013
  Purpose

This phase II trial is studying how well giving bevacizumab together with radiation therapy and cisplatin works in treating patients with previously untreated locally advanced cervical 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 cervical cancer by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with radiation therapy and cisplatin may kill more tumor cells.


Condition Intervention Phase
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
Radiation: external beam radiation therapy
Radiation: brachytherapy
Biological: bevacizumab
Drug: cisplatin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE II STUDY OF BEVACIZUMAB IN COMBINATION WITH DEFINITIVE RADIOTHERAPY AND CISPLATIN CHEMOTHERAPY IN UNTREATED PATIENTS WITH LOCALLY ADVANCED CERVICAL CARCINOMA

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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. [ Time Frame: From start of treatment to 90 days. ] [ Designated as safety issue: Yes ]
    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%.


Secondary Outcome Measures:
  • Treatment-related SAEs and AEs as Assessed by CTCAE v. 3.0 Criteria at Any Time. [ Time Frame: From start of treatment to end of follow-up ] [ Designated as safety issue: Yes ]
  • Disease-free Survival (Failure: Local, Regional or Distant Failure, or Death Due to Any Cause) [ Time Frame: From registration to date of failure (any tumor recurrence, development of distant metastases, or death) or last follow-up. Analysis occurs after all patients have been potentially followed for 2 years. ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.

  • Overall Survival (Failure: Death Due to Any Cause) [ Time Frame: From registration to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for two years. ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.


Enrollment: 60
Study Start Date: August 2006
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (radiation therapy, bevacizumab, cisplatin)

Patients undergo pelvic 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.

Radiation: external beam radiation therapy
Undergo EBRT
Radiation: brachytherapy
Undergo brachytherapy
Biological: bevacizumab
Given IV
Drug: cisplatin
Given IV

Detailed Description:

PRIMARY OBJECTIVES:

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 radiotherapy.

SECONDARY OBJECTIVES:

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 cause).

III. Evaluate overall survival (death due to any cause). IV. Implement the image-based brachytherapy guidelines proposed by the Transatlantic Image-Guided Brachytherapy Working Group.

V. Collect CT scan 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 complications.

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.

  Eligibility

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

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 lymph nodes
    • 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 collection
  • 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 disease
    • 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
  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: NCT00369122

  Show 64 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Tracey Schefter Radiation Therapy Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00369122     History of Changes
Obsolete Identifiers: NCT01530633
Other Study ID Numbers: NCI-2009-00722, NCI-2009-00722, CDR0000493005, RTOG 0417, RTOG-0417, U10CA021661
Study First Received: August 24, 2006
Results First Received: March 5, 2013
Last Updated: September 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Carcinoma, Adenosquamous
Carcinoma, Squamous Cell
Uterine Cervical Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Complex and Mixed
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Uterine Neoplasms
Bevacizumab
Cisplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014