Clinical trial NCT00012012: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 45
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Rate of Acute Grade 3/4 Toxicity (Excluding Grade 3 Leukopenia)
timeFrame: From start of treatment to 90 days
measure: Number of Patients With Acute Grade 3/4 Toxicity (Excluding Grade 3 Leukopenia)
timeFrame: From start of treatment to 90 days
Secondary outcomes:
measure: Pelvic Tumor Control
timeFrame: From registration to date of pelvic tumor failure or last follow-up. Analysis occurs after all patients have been potentially followed for 2 years.
measure: Distant Metastases
timeFrame: From registration to date of distant mets or last follow-up. Analysis occurs after all patients have been potentially followed for 2 years.
Other outcomes:
Locations:
city: Jacksonville Beach
country: United States
facility: Integrated Community Oncology Network
state: Florida
city: Jacksonville
country: United States
facility: Baptist Cancer Institute - Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Florida Oncology Associates at Southside Cancer Center
state: Florida
city: Jascksonville
country: United States
facility: Baptist Medical Center South
state: Florida
city: Orange Park
country: United States
facility: Florida Oncology Associates
state: Florida
city: Palatka
country: United States
facility: Florida Cancer Center - Palatka
state: Florida
city: Saint Augustine
country: United States
facility: Flagler Cancer Center
state: Florida
city: Kalamazooaa
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Las Vegas
country: United States
facility: CCOP - Nevada Cancer Research Foundation
state: Nevada
city: Marlton
country: United States
facility: Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
state: New Jersey
city: Vineland
country: United States
facility: Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
state: New Jersey
city: Akron
country: United States
facility: Akron City Hospital
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Pittsburgh
country: United States
facility: Mercy Cancer Institute at Mercy Hospital
state: Pennsylvania
Study officials:
affiliation: Robert H. Lurie Cancer Center
name: William Small, MD
role: STUDY_CHAIR
References:
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.
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.
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.