Radiation Therapy and Cisplatin With or Without Amifostine for Patients With Stage IIIB or IVA Cervical Cancer

December 24, 2014 updated by: Radiation Therapy Oncology Group

A Two Part Phase I/II Study Of Extended Field External Irradiation And Intracavitary Brachytherapy Combined With Chemotherapy And Amifostine In Carcinoma Of The Cervix With Positive Para-Aortic Or High Common Iliac Lymph Nodes

RATIONALE: Drugs used in chemotherapy, such as cisplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. Drugs such as amifostine may protect normal cells from the side effects of radiation therapy.

PURPOSE: Phase I/II trial to study the effectiveness of combining cisplatin and radiation therapy with or without amifostine in treating patients who have stage IIIB or stage IVA cancer of the cervix.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the feasibility and tolerability of external beam radiotherapy, brachytherapy, and cisplatin in patients with para-aortic or high common iliac lymph node-positive carcinoma of the uterine cervix.
  • Determine the feasibility and tolerability of this regimen with the addition of amifostine in these patients.
  • Determine the efficacy of these 2 regimens, in terms of improving pelvic and para-aortic tumor control and distant metastases, in these patients.

OUTLINE:

  • Phase I: Patients undergo external beam radiotherapy to the pelvis and para-aortic region 5 days a week for 5 weeks. Patients also undergo either intracavitary low-dose rate (LDR) brachytherapy in 2 applications beginning within 2 weeks after completion of external beam radiotherapy at 2-3 week intervals or 6 fractions of high-dose rate intracavitary brachytherapy over 8 weeks beginning as early as week 2 of external beam radiotherapy. Patients also receive cisplatin IV over 1 hour weekly for 6 weeks concurrently with external beam radiotherapy and once with LDR brachytherapy. Phase II proceeds only if toxicity in phase I is within expected parameters.
  • Phase II: Patients receive external beam radiotherapy, brachytherapy, and cisplatin as in phase I. Patients also receive amifostine subcutaneously daily just before external beam radiotherapy and cisplatin. Treatment continues for up to 8 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Baptist Cancer Institute - Jacksonville
      • Jacksonville, Florida, United States, 32207
        • Florida Oncology Associates at Southside Cancer Center
      • Jacksonville Beach, Florida, United States, 32250
        • Integrated Community Oncology Network
      • Jascksonville, Florida, United States, 32258
        • Baptist Medical Center South
      • Orange Park, Florida, United States, 32073
        • Florida Oncology Associates
      • Palatka, Florida, United States, 32177
        • Florida Cancer Center - Palatka
      • Saint Augustine, Florida, United States, 32086
        • Flagler Cancer Center
    • Michigan
      • Kalamazoo, Michigan, United States, 49007
        • Bronson Methodist Hospital
      • Kalamazoo, Michigan, United States, 49007-3731
        • West Michigan Cancer Center
      • Kalamazooaa, Michigan, United States, 49001
        • Borgess Medical Center
    • Nevada
      • Las Vegas, Nevada, United States, 89102
        • University Medical Center of Southern Nevada
      • Las Vegas, Nevada, United States, 89106
        • CCOP - Nevada Cancer Research Foundation
    • New Jersey
      • Marlton, New Jersey, United States, 08053
        • Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
      • Vineland, New Jersey, United States, 08360
        • Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
    • Ohio
      • Akron, Ohio, United States, 44309-2090
        • Akron City Hospital
      • Wooster, Ohio, United States, 44691
        • Cancer Treatment Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15219
        • Mercy Cancer Institute at Mercy Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

DISEASE CHARACTERISTICS:

  • Histologically proven, locally advanced carcinoma of the uterine cervix

    • TNM classification stage IIIB or IVA

    • Disease metastatic to para-aortic or high common iliac lymph nodes

      • Prior complete surgical resection of involved lymph nodes or gross residual tumor involvement of a lymph node allowed

    • The following cellular types are eligible:

      • Squamous cell carcinoma
      • Adenocarcinoma
      • Adenosquamous carcinoma

    • The following cellular types are ineligible:

      • Small cell carcinoma
      • Carcinoid tumor
      • Glassy cell carcinoma
      • Clear cell carcinoma
      • Cystadenocarcinoma
  • No metastatic disease outside of the pelvis (except to the para-aortic nodes)

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-1

Life expectancy

  • At least 6 months

Hematopoietic

  • White blood cell count (WBC) at least 3,000/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic

  • Bilirubin no greater than 1.5 mg/dL
  • Alanine amino transferase (ALT) no greater than 2 times normal

Renal

  • Creatinine no greater than 1.5 mg/dL (urinary diversion allowed)
  • Corrected calcium normal

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No concurrent significant medical condition that would preclude study participation
  • No insulin-dependent diabetes
  • No other malignancy within the past 3 years except cutaneous basal cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior systemic chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior pelvic irradiation except transvaginal radiotherapy to control bleeding

Surgery

  • See Disease Characteristics
  • No prior tumor-directed surgery except lymph node biopsy/staging

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Radiation therapy plus cisplatin
Patients receive extended field external beam radiation therapy (RT) to the para-aortic region and pelvis, intracavitary brachytherapy with concurrent weekly cisplatin.
Drug: Cisplatin
Cisplatin will be given weekly with external beam radiation therapy and once with brachytherapy for a total of six doses. Patients receive 40 mg/m^2 by IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36.
Radiation: Intracavitary brachytherapy
For low dose rate (LDR) brachytherapy, cesium will be given in one to two intracavitary applications, within two weeks of completion of external radiation. The interval between the two applications will be one to three weeks. It is recommended that the total course of treatment be completed in less than eight weeks. High dose rate (HDR) brachytherapy may start as early as week two of external radiation. The minimum cumulative external and intracavitary dose should be 85 Gy.
Radiation: External beam radiation therapy
Patients will receive 1.8 Gy daily for five weeks for a total dose of 45 Gy; involved lateral parametrium and/or pelvic nodes should be boosted for a total dose (including intracavitary treatment) of 60 Gy ± 5%.
EXPERIMENTAL: Radiation therapy plus cisplatin and amifostine
Patients receive extended field external beam radiation therapy (RT) to the para-aortic region and pelvis, intracavitary brachytherapy with concurrent weekly cisplatin and amifostine trihydrate.
Drug: Cisplatin
Cisplatin will be given weekly with external beam radiation therapy and once with brachytherapy for a total of six doses. Patients receive 40 mg/m^2 by IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36.
Radiation: Intracavitary brachytherapy
For low dose rate (LDR) brachytherapy, cesium will be given in one to two intracavitary applications, within two weeks of completion of external radiation. The interval between the two applications will be one to three weeks. It is recommended that the total course of treatment be completed in less than eight weeks. High dose rate (HDR) brachytherapy may start as early as week two of external radiation. The minimum cumulative external and intracavitary dose should be 85 Gy.
Radiation: External beam radiation therapy
Patients will receive 1.8 Gy daily for five weeks for a total dose of 45 Gy; involved lateral parametrium and/or pelvic nodes should be boosted for a total dose (including intracavitary treatment) of 60 Gy ± 5%.
Drug: Amifostine trihydrate
Amifostine will be delivered before each radiation treatment. Amifostine (500 mg) will be given as two equally-divided subcutaneous injections.
Other Names:
  • ethanethiol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Acute Grade 3/4 Toxicity (Excluding Grade 3 Leukopenia)
Time Frame: From start of treatment to 90 days
To determine the feasibility and tolerance of extended-field external radiotherapy to the pelvis and para-aortic region and intracavitary irradiation combined with weekly cisplatin using the rate of acute grade 3/4 toxicity rate (excluding grade 3 leukopenia). The first part of this study was designed to determine the acute grade 3/4 toxicity rate (excluding grade 3 leukopenia), to have a starting point for the second part (second arm) of the study.
From start of treatment to 90 days
Number of Patients With Acute Grade 3/4 Toxicity (Excluding Grade 3 Leukopenia)
Time Frame: From start of treatment to 90 days
The second part of this study (second arm) was designed to detect a 40% relative reduction (absolute from 77% to 46%) in the acute grade 3/4 toxicity (excluding grade 3 leukopenia) rate, with the addition of amifostine. A one-sided alpha of 0.05 and 80% power required 16 evaluable patients to detect the hypothesized difference. If ≤ 8 had the toxicity, it would be concluded that adding amifostine decreased this toxicity rate by at least 40%.
From start of treatment to 90 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Pelvic Tumor Control
Time Frame: From registration to date of pelvic tumor failure or last follow-up. Analysis occurs after all patients have been potentially followed for 2 years.
From registration to date of pelvic tumor failure or last follow-up. Analysis occurs after all patients have been potentially followed for 2 years.
Distant Metastases
Time Frame: From registration to date of distant mets or last follow-up. Analysis occurs after all patients have been potentially followed for 2 years.
From registration to date of distant mets or last follow-up. Analysis occurs after all patients have been potentially followed for 2 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radiation Therapy Oncology Group

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2001

Primary Completion (ACTUAL)

September 1, 2007

Study Completion (ACTUAL)

June 1, 2010

Study Registration Dates

First Submitted

March 3, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (ESTIMATE)

January 27, 2003

Study Record Updates

Last Update Posted (ESTIMATE)

January 7, 2015

Last Update Submitted That Met QC Criteria

December 24, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RTOG-0116
  • CDR0000068472

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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