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

Primary Purpose

Cervical Cancer, Radiation Toxicity

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Amifostine trihydrate
Cisplatin
Intracavitary brachytherapy
External beam radiation therapy
Sponsored by
Radiation Therapy Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cervical Cancer focused on measuring radiation toxicity, stage III cervical cancer, stage IVA cervical cancer, cervical squamous cell carcinoma, cervical adenocarcinoma, cervical adenosquamous cell carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Integrated Community Oncology Network
  • Baptist Cancer Institute - Jacksonville
  • Florida Oncology Associates at Southside Cancer Center
  • Baptist Medical Center South
  • Florida Oncology Associates
  • Florida Cancer Center - Palatka
  • Flagler Cancer Center
  • Borgess Medical Center
  • West Michigan Cancer Center
  • Bronson Methodist Hospital
  • University Medical Center of Southern Nevada
  • CCOP - Nevada Cancer Research Foundation
  • Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
  • Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
  • Akron City Hospital
  • Cancer Treatment Center
  • Mercy Cancer Institute at Mercy Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Radiation therapy plus cisplatin

Radiation therapy plus cisplatin and amifostine

Arm Description

Patients receive extended field external beam radiation therapy (RT) to the para-aortic region and pelvis, intracavitary brachytherapy with concurrent weekly cisplatin.

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.

Outcomes

Primary Outcome Measures

Rate of Acute Grade 3/4 Toxicity (Excluding Grade 3 Leukopenia)
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)
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
Distant Metastases

Full Information

First Posted
March 3, 2001
Last Updated
December 24, 2014
Sponsor
Radiation Therapy Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00012012
Brief Title
Radiation Therapy and Cisplatin With or Without Amifostine for Patients With Stage IIIB or IVA Cervical Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
August 2001 (undefined)
Primary Completion Date
September 2007 (Actual)
Study Completion Date
June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radiation Therapy Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Cancer, Radiation Toxicity
Keywords
radiation toxicity, stage III cervical cancer, stage IVA cervical cancer, cervical squamous cell carcinoma, cervical adenocarcinoma, cervical adenosquamous cell carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Radiation therapy plus cisplatin
Arm Type
Experimental
Arm Description
Patients receive extended field external beam radiation therapy (RT) to the para-aortic region and pelvis, intracavitary brachytherapy with concurrent weekly cisplatin.
Arm Title
Radiation therapy plus cisplatin and amifostine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Amifostine trihydrate
Other Intervention Name(s)
ethanethiol
Intervention Description
Amifostine will be delivered before each radiation treatment. Amifostine (500 mg) will be given as two equally-divided subcutaneous injections.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Intracavitary brachytherapy
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
External beam radiation therapy
Intervention Description
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%.
Primary Outcome Measure Information:
Title
Rate of Acute Grade 3/4 Toxicity (Excluding Grade 3 Leukopenia)
Description
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.
Time Frame
From start of treatment to 90 days
Title
Number of Patients With Acute Grade 3/4 Toxicity (Excluding Grade 3 Leukopenia)
Description
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%.
Time Frame
From start of treatment to 90 days
Secondary Outcome Measure Information:
Title
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.
Title
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.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William Small, MD
Organizational Affiliation
Robert H. Lurie Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Integrated Community Oncology Network
City
Jacksonville Beach
State/Province
Florida
ZIP/Postal Code
32250
Country
United States
Facility Name
Baptist Cancer Institute - Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Florida Oncology Associates at Southside Cancer Center
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Baptist Medical Center South
City
Jascksonville
State/Province
Florida
ZIP/Postal Code
32258
Country
United States
Facility Name
Florida Oncology Associates
City
Orange Park
State/Province
Florida
ZIP/Postal Code
32073
Country
United States
Facility Name
Florida Cancer Center - Palatka
City
Palatka
State/Province
Florida
ZIP/Postal Code
32177
Country
United States
Facility Name
Flagler Cancer Center
City
Saint Augustine
State/Province
Florida
ZIP/Postal Code
32086
Country
United States
Facility Name
Borgess Medical Center
City
Kalamazooaa
State/Province
Michigan
ZIP/Postal Code
49001
Country
United States
Facility Name
West Michigan Cancer Center
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007-3731
Country
United States
Facility Name
Bronson Methodist Hospital
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007
Country
United States
Facility Name
University Medical Center of Southern Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89102
Country
United States
Facility Name
CCOP - Nevada Cancer Research Foundation
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89106
Country
United States
Facility Name
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
City
Marlton
State/Province
New Jersey
ZIP/Postal Code
08053
Country
United States
Facility Name
Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
City
Vineland
State/Province
New Jersey
ZIP/Postal Code
08360
Country
United States
Facility Name
Akron City Hospital
City
Akron
State/Province
Ohio
ZIP/Postal Code
44309-2090
Country
United States
Facility Name
Cancer Treatment Center
City
Wooster
State/Province
Ohio
ZIP/Postal Code
44691
Country
United States
Facility Name
Mercy Cancer Institute at Mercy Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15219
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22193645
Citation
Viswanathan AN, Moughan J, Small W Jr, Levenback C, Iyer R, Hymes S, Dicker AP, Miller B, Erickson B, Gaffney DK. The quality of cervical cancer brachytherapy implantation and the impact on local recurrence and disease-free survival in radiation therapy oncology group prospective trials 0116 and 0128. Int J Gynecol Cancer. 2012 Jan;22(1):123-31. doi: 10.1097/IGC.0b013e31823ae3c9.
Results Reference
background
PubMed Identifier
21892091
Citation
Small W Jr, Winter K, Levenback C, Iyer R, Hymes SR, Jhingran A, Gaffney D, Erickson B, Greven K. Extended-field irradiation and intracavitary brachytherapy combined with cisplatin and amifostine for cervical cancer with positive para-aortic or high common iliac lymph nodes: results of arm II of Radiation Therapy Oncology Group (RTOG) 0116. Int J Gynecol Cancer. 2011 Oct;21(7):1266-75. doi: 10.1097/IGC.0b013e31822c2769.
Results Reference
result
PubMed Identifier
17398031
Citation
Small W Jr, Winter K, Levenback C, Iyer R, Gaffney D, Asbell S, Erickson B, Jhingran A, Greven K. 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 1 of RTOG 0116. Int J Radiat Oncol Biol Phys. 2007 Jul 15;68(4):1081-7. doi: 10.1016/j.ijrobp.2007.01.026. Epub 2007 Mar 29.
Results Reference
result

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

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