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

Cervical Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00012012
• Other study ID #: RTOG-0116
• Secondary ID: CDR0000068472
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 3, 2001
• Last updated: December 24, 2014
• Start date: August 2001
• Est. completion date: June 2010

Study information

• Verified date: December 2014
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: June 2010
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cervical Cancer
• Radiation Injuries
• Radiation Toxicity
• Uterine Cervical Neoplasms

Intervention

Drug:
• Amifostine trihydrate
Amifostine will be delivered before each radiation treatment. Amifostine (500 mg) will be given as two equally-divided subcutaneous injections.
• 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.
• 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%.

Locations

Country	Name	City	State
United States	Akron City Hospital	Akron	Ohio
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	Florida Oncology Associates at Southside Cancer Center	Jacksonville	Florida
United States	Integrated Community Oncology Network	Jacksonville Beach	Florida
United States	Baptist Medical Center South	Jascksonville	Florida
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Borgess Medical Center	Kalamazooaa	Michigan
United States	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey
United States	Florida Oncology Associates	Orange Park	Florida
United States	Florida Cancer Center - Palatka	Palatka	Florida
United States	Mercy Cancer Institute at Mercy Hospital	Pittsburgh	Pennsylvania
United States	Flagler Cancer Center	Saint Augustine	Florida
United States	Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare	Vineland	New Jersey
United States	Cancer Treatment Center	Wooster	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (4)

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 — View 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 commo — View Citation

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. [Abstrac

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From start of treatment to 90 days	Yes
Primary	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%.	From start of treatment to 90 days	Yes
Secondary	Pelvic Tumor Control		From registration to date of pelvic tumor failure or last follow-up. Analysis occurs after all patients have been potentially followed for 2 years.	No
Secondary	Distant Metastases		From registration to date of distant mets or last follow-up. Analysis occurs after all patients have been potentially followed for 2 years.	No