Clinical trial NCT00331760: Intensity-Modulated Radiation Therapy to the Pelvis With or Without Chemotherapy in Treating Patients With Endometrial Cancer or Cervical Cancer That Has Been Removed By Surgery
Official title: A Phase II Study of Intensity Modulated Radiation Therapy (IMRT) to the Pelvis ± Chemotherapy for Post-Operative Patients With Either Endometrial or Cervical Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cervical Cancer
Endometrial Cancer
Keywords: stage I endometrial carcinoma
stage II endometrial carcinoma
stage III endometrial carcinoma
endometrial adenoacanthoma
endometrial adenocarcinoma
endometrial adenosquamous cell carcinoma
stage IB cervical cancer
stage IIA cervical cancer
stage IIB cervical cancer
cervical adenocarcinoma
cervical adenosquamous cell carcinoma
cervical squamous cell carcinoma
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: NRG Oncology
First posted: 2006-05-31
Enrollment: 106
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Specialized radiation therapy (RT), such as intensity-modulated radiation therapy (IMRT), that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving intensity-modulated radiation therapy to the pelvis with or without chemotherapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well intensity-modulated radiation therapy to the pelvis with or without chemotherapy works in treating patients with endometrial cancer or cervical cancer that has been removed by surgery.

Detailed description: OBJECTIVES:

* Determine the transportability of intensity modulated radiotherapy (IMRT) to a multi-institutional setting in patients with resected endometrial or cervical cancer.
* Compare the efficacy, in terms of reducing short-term bowel injury, of IMRT versus standard treatments.
* Assess adverse events related to this regimen.
* Estimate the rates of local-regional control, distant metastasis, and disease-free and overall survival.
* Evaluate chemotherapy compliance with this regimen for patients with cervical carcinoma.

OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis (cervical vs endometrial cancer).

All patients undergo intensity modulated radiotherapy (IMRT) once a day, 5 days a week, for 5.5 weeks. Patients with cervical cancer also receive cisplatin IV over 30-60 minutes on day 1 or 2. Treatment with cisplatin repeats every 7 days for 5 courses (during radiotherapy) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 6 weeks post-IMRT and then every 3 months for 2 years, every 6 months for years 3-5, and then annually for at least 3 years.

PROJECTED ACCRUAL: A total of 92 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Must have undergone a hysterectomy (total abdominal, vaginal, radical, or laparoscopic-assisted vaginal) within 7 weeks prior to study entry

  * Patients with endometrial cancer must have also undergone a bilateral salpingo-oophorectomy
* Histologically confirmed diagnosis of 1 of the following:

  * Endometrial cancer meeting 1 of the following criteria:

    * Stage IB grade 3, IC grade 1-3, IIA, or IIB disease requiring postoperative pelvic radiotherapy
    * Unstaged (no lymph node dissection or sampling) stage IB grade 2 disease
    * Stage IIIC with all of the following:

      * Pelvic lymph node positive only
      * Para-aortic nodes sampled negative
      * Not receiving chemotherapy
  * Cervical cancer meeting 1 of the following criteria:

    * Post-radical hysterectomy and requires postoperative pelvic radiotherapy due to any of the following:

      * Positive pelvic nodes (negative para-aortic nodes)
      * Microscopic parametrial involvement and negative margins
      * Disease qualified by Sedlis criteria must have 2 of the following risk factors:

        * 1/3 or more stromal invasion
        * Lymph-vascular space invasion
        * Large clinical tumor diameter (≥ 4 cm)
    * Post-simple hysterectomy with negative margins and negative nodes by CT scan, MRI, or positron emission tomography-CT scan
* No requirement for extended-field radiotherapy beyond the pelvis
* No histologically confirmed papillary serous, clear cell, or neuroendocrine (either large or small cell) disease, endometrial stromal sarcoma, leiomyosarcoma, or malignant müllerian mixed tumor
* No evidence of metastatic disease outside of the pelvis
* No microscopic involvement of the resection margin (\< 3 mm)

PATIENT CHARACTERISTICS:

* Zubrod performance status 0-2
* WBC (white blood cell count) ≥ 4,000/mm³ (cervical cancer patients only)
* Absolute neutrophil count ≥ 1,800/mm³ (cervical cancer patients only)
* Platelet count ≥ 100,000/mm³ (cervical cancer patients only)
* Hemoglobin ≥ 8.0 g/dL (transfusion allowed)
* Serum creatinine ≤ 2.0 mg/dL (cervical cancer patients only)
* Creatinine clearance ≥ 50 mL/min (cervical cancer patients only)
* AST (aspartate aminotransferase) ≤ 2 times upper limit of normal
* Bilirubin ≤ 2 times upper limit of normal
* Patients must not exceed the weight and size limits of the treatment table or CT scanner

  * No mental status changes or bladder control problems that would preclude study compliance with bladder-filling instructions
* No active inflammatory bowel disease
* No severe, active, concurrent illness, defined as any of the following:

  * Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
  * Transmural myocardial infarction within the past 6 months
  * Acute bacterial or fungal infection requiring IV antibiotics
  * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
  * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  * AIDS
* No history of allergy to cisplatin (cervical cancer patients)
* No prior invasive malignancy (except nonmelanoma skin cancer) unless disease-free for ≥ 3 years

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior radiotherapy to the pelvis that would result in overlap of radiotherapy fields
* No prior platinum-based chemotherapy (cervical cancer patients)
* No concurrent prophylactic growth factors (e.g., filgrastim \[G-CSF\], sargramostim \[GM-CSF\], or pegfilgrastim)
* No concurrent prophylactic thrombopoietic agents
* No concurrent amifostine or other protective agents

Primary outcomes:
measure: Reproducibility of Radiation Technique (Number of Unacceptable Deviations in Central IMRT Quality Assurance Review)
timeFrame: IMRT planning and dosing data is centrally reviewed for quality assurance after treatment delivery.
Secondary outcomes:
measure: Percentage of Patients With Grade 2+ Bowel Adverse Events
timeFrame: From the start of treatment to 90 days.
measure: Percentage of Patients With Any Grade 3+ Treatment-related Adverse Events
timeFrame: From start of treatment to the end of follow-up. Maximum follow-up at time of analysis was 10.2 years for endometrium cancer patients and 9.5 years for cervical cancer patients.
measure: Percentage of Patients With Any Late Grade 3+ Treatment-related Adverse Events
timeFrame: From 91 days after start of study treatment to the end of follow-up. Maximum follow-up at time of analysis was 10.2 years for endometrium cancer patients and 9.5 years for cervical cancer patients.
measure: Percentage of Cervical Carcinoma Patients That Were Chemotherapy Compliant
timeFrame: From start to end of chemotherapy, approximately five weeks from registration.
measure: Rate of Local-regional Failure at Five Years
timeFrame: From registration to five years.
measure: Rate of Distant Metastases at Five Years
timeFrame: From registration to five years
measure: Rate of Disease-free Survival at Five Years
timeFrame: From registration five years
measure: Rate of Overall Survival at Five Years
timeFrame: From randomization to five years
Other outcomes:
Locations:
city: Auburn
country: United States
facility: Auburn Radiation Oncology
state: California
city: Cameron Park
country: United States
facility: Radiation Oncology Centers - Cameron Park
state: California
city: Carmichael
country: United States
facility: Mercy Cancer Center at Mercy San Juan Medical Center
state: California
city: Castro Valley
country: United States
facility: East Bay Radiation Oncology Center
state: California
city: Castro Valley
country: United States
facility: Eden Medical Center
state: California
city: Castro Valley
country: United States
facility: Valley Medical Oncology Consultants - Castro Valley
state: California
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Fremont
country: United States
facility: Valley Medical Oncology
state: California
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Oakland
country: United States
facility: Highland General Hospital
state: California
city: Oakland
country: United States
facility: Alta Bates Summit Medical Center - Summit Campus
state: California
city: Oakland
country: United States
facility: Bay Area Breast Surgeons, Incorporated
state: California
city: Oakland
country: United States
facility: CCOP - Bay Area Tumor Institute
state: California
city: Oakland
country: United States
facility: Larry G Strieff MD Medical Corporation
state: California
city: Oakland
country: United States
facility: Tom K Lee, Incorporated
state: California
city: Pleasanton
country: United States
facility: Valley Care Medical Center
state: California
city: Pleasanton
country: United States
facility: Valley Medical Oncology Consultants - Pleasanton
state: California
city: Roseville
country: United States
facility: Radiation Oncology Center - Roseville
state: California
city: Sacramento
country: United States
facility: Radiological Associates of Sacramento Medical Group, Incorporated
state: California
city: Sacramento
country: United States
facility: Mercy General Hospital
state: California
city: San Diego
country: United States
facility: Veterans Affairs Medical Center - San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: San Pablo
country: United States
facility: Doctors Medical Center - San Pablo Campus
state: California
city: Vacaville
country: United States
facility: Solano Radiation Oncology Center
state: California
city: Lewes
country: United States
facility: Tunnell Cancer Center at Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Panama City
country: United States
facility: Bay Medical
state: Florida
city: Bloomington
country: United States
facility: St. Joseph Medical Center
state: Illinois
city: Canton
country: United States
facility: Graham Hospital
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Elk Grove Village
country: United States
facility: Alexian Brothers Radiation Oncology
state: Illinois
city: Eureka
country: United States
facility: Eureka Community Hospital
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Clinic, PC
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Cottage Hospital
state: Illinois
city: Galesburg
country: United States
facility: InterCommunity Cancer Center of Western Illinois
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Hopedale
country: United States
facility: Hopedale Medical Complex
state: Illinois
city: Macomb
country: United States
facility: McDonough District Hospital
state: Illinois
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center at Loyola University Medical Center
state: Illinois
city: Normal
country: United States
facility: BroMenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center
state: Illinois
city: Olympia Fields
country: United States
facility: Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
state: Illinois
city: Ottawa
country: United States
facility: Community Hospital of Ottawa
state: Illinois
city: Ottawa
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Ottawa
state: Illinois
city: Pekin
country: United States
facility: Cancer Treatment Center at Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Peoria
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Peoria
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Community Hospital
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Spring Valley
country: United States
facility: St. Margaret's Hospital
state: Illinois
city: Spring Valley
country: United States
facility: Valley Cancer Center
state: Illinois
city: Springfield
country: United States
facility: Cancer Institute at St. John's Hospital
state: Illinois
city: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers - Beech Grove Campus
state: Indiana
city: Hammond
country: United States
facility: Oncology Center at Saint Margaret Mercy Healthcare Center
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital & Health Care Services
state: Indiana
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: Providence Medical Center
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Overland Park
country: United States
facility: Menorah Medical Center
state: Kansas
city: Overland Park
country: United States
facility: Johnson County Radiation Therapy
state: Kansas
city: Shawnee Mission
country: United States
facility: Shawnee Mission Medical Center
state: Kansas
city: Lewiston
country: United States
facility: Central Maine Comprehensive Cancer Center at Central Maine Medical Center
state: Maine
city: Elkton
country: United States
facility: Union Hospital Cancer Program at Union Hospital
state: Maryland
city: Boston
country: United States
facility: Dana-Farber/Brigham and Women's Cancer Center
state: Massachusetts
city: Quincy
country: United States
facility: South Suburban Oncology Center
state: Massachusetts
city: South Weymouth
country: United States
facility: South Shore Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Kalamazoo
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: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Cape Girardeau
country: United States
facility: Cancer Institute of Cape Girardeau, LLC
state: Missouri
city: Independence
country: United States
facility: Independence Regional Health Center
state: Missouri
city: Kansas City
country: United States
facility: Truman Medical Center - Hospital Hill
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute at Saint Luke's Hospital
state: Missouri
city: Kansas City
country: United States
facility: Kansas City Cancer Center at St. Joseph's Medical Mall
state: Missouri
city: Kansas City
country: United States
facility: St. Joseph Medical Center
state: Missouri
city: Kansas City
country: United States
facility: North Kansas City Hospital
state: Missouri
city: Kansas City
country: United States
facility: Parvin Radiation Oncology
state: Missouri
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Kansas City
country: United States
facility: Radiation Oncology Associates of Kansas City at Northland Radiation Oncology Center
state: Missouri
city: Saint Joseph
country: United States
facility: Heartland Regional Medical Center
state: Missouri
city: Springfield
country: United States
facility: CCOP - Cancer Research for the Ozarks
state: Missouri
city: Springfield
country: United States
facility: St. John's Regional Health Center
state: Missouri
city: Springfield
country: United States
facility: Hulston Cancer Center at Cox Medical Center South
state: Missouri
city: Camden
country: United States
facility: Cancer Institute of New Jersey at Cooper University Hospital - Camden
state: New Jersey
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Saint Peter's University Hospital
state: New Jersey
city: Vineland
country: United States
facility: Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
state: New Jersey
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at Cooper - Voorhees
state: New Jersey
city: Albuquerque
country: United States
facility: Lovelace Medical Center - Downtown
state: New Mexico
city: Albuquerque
country: United States
facility: Radiation Oncology Associates, PA
state: New Mexico
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Santa Fe
country: United States
facility: Cancer Institute of New Mexico
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center - Petrie Division
state: New York
city: New York
country: United States
facility: St. Luke's - Roosevelt Hospital Center - St.Luke's Division
state: New York
city: Charlotte
country: United States
facility: Presbyterian Cancer Center at Presbyterian Hospital
state: North Carolina
city: Akron
country: United States
facility: McDowell Cancer Center at Akron General Medical Center
state: Ohio
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Huron Hospital Cancer Care Center
state: Ohio
city: Cleveland
country: United States
facility: Euclid Hospital
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: Veterans Affairs Medical Center - Dayton
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Medical Associates
state: Ohio
city: Franklin
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Mayfield Heights
country: United States
facility: Hillcrest Cancer Center at Hillcrest Hospital
state: Ohio
city: Salem
country: United States
facility: Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Warrensville Heights
country: United States
facility: South Pointe Hospital Cancer Care Center
state: Ohio
city: Wilmington
country: United States
facility: Clinton Memorial Hospital
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Drexel Hill
country: United States
facility: Delaware County Regional Cancer Center at Delaware County Memorial Hospital
state: Pennsylvania
city: Paoli
country: United States
facility: Cancer Center of Paoli Memorial Hospital
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - Main Line Health
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Cancer Center at Lankenau Hospital
state: Pennsylvania
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Kingsport
country: United States
facility: Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
state: Tennessee
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: American Fork
country: United States
facility: American Fork Hospital
state: Utah
city: Cedar City
country: United States
facility: Sandra L. Maxwell Cancer Center
state: Utah
city: Murray
country: United States
facility: Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
state: Utah
city: Ogden
country: United States
facility: Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center - Provo
state: Utah
city: Saint George
country: United States
facility: Dixie Regional Medical Center - East Campus
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists at UCS Cancer Center
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at University of Utah
state: Utah
city: Burlington
country: United States
facility: Fletcher Allen Health Care - University Health Center Campus
state: Vermont
city: Norton
country: United States
facility: Southwest Virginia Regional Cancer Center at Wellmonth Health
state: Virginia
city: Seattle
country: United States
facility: CCOP - Virginia Mason Research Center
state: Washington
city: La Crosse
country: United States
facility: Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
city: Mequon
country: United States
facility: Columbia Saint Mary's Hospital - Ozaukee
state: Wisconsin
city: Milwaukee
country: United States
facility: Columbia-Saint Mary's Cancer Care Center
state: Wisconsin
city: Wausau
country: United States
facility: University of Wisconcin Cancer Center at Aspirus Wausau Hospital
state: Wisconsin
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill Cancer Centre at McGill University
state: Quebec
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Anuja Jhingran, MD
role: STUDY_CHAIR
References:
citation: Jhingran A, Winter K, Portelance L, Miller B, Salehpour M, Gaur R, Souhami L, Small W Jr, Berk L, Gaffney D. A phase II study of intensity modulated radiation therapy to the pelvis for postoperative patients with endometrial carcinoma: radiation therapy oncology group trial 0418. Int J Radiat Oncol Biol Phys. 2012 Sep 1;84(1):e23-8. doi: 10.1016/j.ijrobp.2012.02.044. Epub 2012 Apr 28.