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

NCT00012012 | Completed Phase 1 Results DMC

• 2 other identifiers: RTOG-0116CDR0000068472
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 17

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (2)

• 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.

• 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.

Study Arms (2)

Radiation therapy plus cisplatin

EXPERIMENTAL

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

Drug: Cisplatin; Radiation: Intracavitary brachytherapy; Radiation: External beam radiation therapy

Radiation therapy plus cisplatin and amifostine

EXPERIMENTAL

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; Drug: Cisplatin; Radiation: Intracavitary brachytherapy; Radiation: External beam radiation therapy

Interventions

Amifostine trihydrate DRUG

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

Also known as: ethanethiol

Radiation therapy plus cisplatin and amifostine

Cisplatin DRUG

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 therapy plus cisplatin; Radiation therapy plus cisplatin and amifostine

Intracavitary brachytherapy RADIATION

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 therapy plus cisplatin; Radiation therapy plus cisplatin and amifostine

External beam radiation therapy RADIATION

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%.

Radiation therapy plus cisplatin; Radiation therapy plus cisplatin and amifostine

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (17)

Baptist Cancer Institute - Jacksonville

Jacksonville, Florida, 32207, United States

Location

Florida Oncology Associates at Southside Cancer Center

Jacksonville, Florida, 32207, United States

Location

Integrated Community Oncology Network

Jacksonville Beach, Florida, 32250, United States

Location

Baptist Medical Center South

Jascksonville, Florida, 32258, United States

Location

Florida Oncology Associates

Orange Park, Florida, 32073, United States

Location

Florida Cancer Center - Palatka

Palatka, Florida, 32177, United States

Location

Flagler Cancer Center

Saint Augustine, Florida, 32086, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007-3731, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

Borgess Medical Center

Kalamazooaa, Michigan, 49001, United States

Location

University Medical Center of Southern Nevada

Las Vegas, Nevada, 89102, United States

Location

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, 89106, United States

Location

Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton

Marlton, New Jersey, 08053, United States

Location

Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare

Vineland, New Jersey, 08360, United States

Location

Akron City Hospital

Akron, Ohio, 44309-2090, United States

Location

Cancer Treatment Center

Wooster, Ohio, 44691, United States

Location

Mercy Cancer Institute at Mercy Hospital

Pittsburgh, Pennsylvania, 15219, United States

Location

Related Publications (3)

• 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.

  PMID: 22193645 BACKGROUND

• 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.

  PMID: 21892091 RESULT

• 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.

  PMID: 17398031 RESULT

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Radiation Injuries

Interventions

Amifostine; ethanethiol; Cisplatin; Brachytherapy

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Organothiophosphates; Organophosphates; Organophosphorus Compounds; Organic Chemicals; Organothiophosphorus Compounds; Sulfur Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Radiotherapy; Therapeutics

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

Study Officials

• William Small, MD

  Robert H. Lurie Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2001
• First Posted: January 27, 2003
• Study Start: August 1, 2001
• Primary Completion: September 1, 2007
• Study Completion: June 1, 2010
• Last Updated: January 7, 2015
• Results First Posted: January 7, 2015

Record last verified: 2014-12

Locations

US (17)