Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00012012
First received: March 3, 2001
Last updated: December 24, 2014
Last verified: December 2014
  Purpose

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.


Condition Intervention Phase
Cervical Cancer
Radiation Toxicity
Drug: Amifostine trihydrate
Drug: Cisplatin
Radiation: Intracavitary brachytherapy
Radiation: External beam radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Rate of Acute Grade 3/4 Toxicity (Excluding Grade 3 Leukopenia) [ Time Frame: From start of treatment to 90 days ] [ Designated as safety issue: Yes ]
    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.

  • Number of Patients With Acute Grade 3/4 Toxicity (Excluding Grade 3 Leukopenia) [ Time Frame: From start of treatment to 90 days ] [ Designated as safety issue: Yes ]
    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%.


Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: August 2001
Study Completion Date: June 2010
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Amifostine trihydrate
Amifostine will be delivered before each radiation treatment. Amifostine (500 mg) will be given as two equally-divided subcutaneous injections.
Other Name: ethanethiol
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%.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00012012

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

Additional Information:
Publications:
Small W, Winter K, Levenback C, et al.: Extended field irradiation and intracavitary brachytherapy combined with cisplatin chemotherapy for cervical cancer with positive para-aortic or high common iliac lymph nodes: results of arm 2 of RTOG 0116. [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): A-10, S5-6, 2007.
Small W, Winter K, Levenback C, et al.: Extended field irradiation and intracavitary brachytherapy combined with cisplatin chemotherapy for cervical cancer with positive para-aortic or high common illiac lymph nodes: results of arm 1 of RTOG 0116. [Abstract] Int J Radiat Oncol Biol Phys 63 (2 Suppl 1): A-156, S94, 2005.

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00012012     History of Changes
Other Study ID Numbers: RTOG-0116, CDR0000068472
Study First Received: March 3, 2001
Results First Received: December 24, 2014
Last Updated: December 24, 2014
Health Authority: United States: Federal Government

Keywords provided by Radiation Therapy Oncology Group:
radiation toxicity
stage III cervical cancer
stage IVA cervical cancer
cervical squamous cell carcinoma
cervical adenocarcinoma
cervical adenosquamous cell carcinoma

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Uterine Neoplasms
Amifostine
Cisplatin
Antineoplastic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Radiation-Protective Agents
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015