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

Cervical Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00331760
• Other study ID #: RTOG-0418
• Secondary ID: CDR0000472905
• Status: Completed
• Phase: Phase 2
• Start date: March 2006
• Est. completion date: December 2016

Study information

• Verified date: February 2019
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 106
• Est. completion date: December 2016
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cervical Cancer
• Endometrial Cancer
• Endometrial Neoplasms
• Uterine Cervical Neoplasms

Intervention

Drug:
• cisplatin

Radiation:
• intensity-modulated radiation therapy

Locations

Country	Name	City	State
Canada	McGill Cancer Centre at McGill University	Montreal	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	Lovelace Medical Center - Downtown	Albuquerque	New Mexico
United States	Radiation Oncology Associates, PA	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	American Fork Hospital	American Fork	Utah
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Auburn Radiation Oncology	Auburn	California
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Dana-Farber/Brigham and Women's Cancer Center	Boston	Massachusetts
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Cancer Institute of New Jersey at Cooper University Hospital - Camden	Camden	New Jersey
United States	Radiation Oncology Centers - Cameron Park	Cameron Park	California
United States	Graham Hospital	Canton	Illinois
United States	Cancer Institute of Cape Girardeau, LLC	Cape Girardeau	Missouri
United States	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California
United States	Memorial Hospital	Carthage	Illinois
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Eden Medical Center	Castro Valley	California
United States	Valley Medical Oncology Consultants - Castro Valley	Castro Valley	California
United States	Sandra L. Maxwell Cancer Center	Cedar City	Utah
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Euclid Hospital	Cleveland	Ohio
United States	Huron Hospital Cancer Care Center	Cleveland	Ohio
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Delaware County Regional Cancer Center at Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Alexian Brothers Radiation Oncology	Elk Grove Village	Illinois
United States	Union Hospital Cancer Program at Union Hospital	Elkton	Maryland
United States	Eureka Community Hospital	Eureka	Illinois
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Valley Medical Oncology	Fremont	California
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	InterCommunity Cancer Center of Western Illinois	Galesburg	Illinois
United States	Oncology Center at Saint Margaret Mercy Healthcare Center	Hammond	Indiana
United States	Mason District Hospital	Havana	Illinois
United States	Hopedale Medical Complex	Hopedale	Illinois
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Independence Regional Health Center	Independence	Missouri
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Kansas City Cancer Center at St. Joseph's Medical Mall	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Parvin Radiation Oncology	Kansas City	Missouri
United States	Providence Medical Center	Kansas City	Kansas
United States	Radiation Oncology Associates of Kansas City at Northland Radiation Oncology Center	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri
United States	St. Joseph Medical Center	Kansas City	Missouri
United States	Truman Medical Center - Hospital Hill	Kansas City	Missouri
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee
United States	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	Central Maine Comprehensive Cancer Center at Central Maine Medical Center	Lewiston	Maine
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	McDonough District Hospital	Macomb	Illinois
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Hillcrest Cancer Center at Hillcrest Hospital	Mayfield Heights	Ohio
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Columbia Saint Mary's Hospital - Ozaukee	Mequon	Wisconsin
United States	Columbia-Saint Mary's Cancer Care Center	Milwaukee	Wisconsin
United States	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	Beth Israel Medical Center - Petrie Division	New York	New York
United States	St. Luke's - Roosevelt Hospital Center - St.Luke's Division	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Southwest Virginia Regional Cancer Center at Wellmonth Health	Norton	Virginia
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Breast Surgeons, Incorporated	Oakland	California
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Larry G Strieff MD Medical Corporation	Oakland	California
United States	Tom K Lee, Incorporated	Oakland	California
United States	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah
United States	Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields	Olympia Fields	Illinois
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	Johnson County Radiation Therapy	Overland Park	Kansas
United States	Menorah Medical Center	Overland Park	Kansas
United States	Bay Medical	Panama City	Florida
United States	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Valley Care Medical Center	Pleasanton	California
United States	Valley Medical Oncology Consultants - Pleasanton	Pleasanton	California
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	South Suburban Oncology Center	Quincy	Massachusetts
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Radiation Oncology Center - Roseville	Roseville	California
United States	Mercy General Hospital	Sacramento	California
United States	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford	Salem	Ohio
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah
United States	Veterans Affairs Medical Center - San Diego	San Diego	California
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Doctors Medical Center - San Pablo Campus	San Pablo	California
United States	Cancer Institute of New Mexico	Santa Fe	New Mexico
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Shawnee Mission Medical Center	Shawnee Mission	Kansas
United States	South Shore Hospital	South Weymouth	Massachusetts
United States	St. Margaret's Hospital	Spring Valley	Illinois
United States	Valley Cancer Center	Spring Valley	Illinois
United States	Cancer Institute at St. John's Hospital	Springfield	Illinois
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	St. John's Regional Health Center	Springfield	Missouri
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Solano Radiation Oncology Center	Vacaville	California
United States	Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare	Vineland	New Jersey
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	South Pointe Hospital Cancer Care Center	Warrensville Heights	Ohio
United States	University of Wisconcin Cancer Center at Aspirus Wausau Hospital	Wausau	Wisconsin
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Cancer Treatment Center	Wooster	Ohio
United States	CCOP - Main Line Health	Wynnewood	Pennsylvania
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (3)

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

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 o — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reproducibility of Radiation Technique (Number of Unacceptable Deviations in Central IMRT Quality Assurance Review)	Central quality assurance review of the IMRT planning and dosing categorized unacceptable deviations (UD) from protocol compliance with the delineation of planning target volume for the vagina and pelvic lymph nodes. Each arm of this study is considered independently, they are not compared to each other. The study was designed such that, for each arm, 5 or more of 42 subjects scored as unacceptable would determine the respective treatment technique as not reproducible. For each arm this design provides 90% power with a 0.05 type I error to reject the null hypothesis that the true probability of concluding the given technique to be reproducible is <= 80%. The alternative hypothesis is that the true probability is >= 95%.; For [vagina / pelvic lymph nodes]: UD is defined as: The 90% isodose surface covers < 95% of [internal target volume (ITV)/ planned target volume (PTV)] 50.4 or > 5% of the [ITV/PTV] 50.4 receives over 115%.	IMRT planning and dosing data is centrally reviewed for quality assurance after treatment delivery.
Secondary	Percentage of Patients With Grade 2+ Bowel Adverse Events	Bowel adverse events are defined as any of the following adverse events: diarrhea; enteritis; fistula; ileus:gastrointestinal (GI); incontinence:anal; necrosis:GI; obstruction:GI; perforation:GI; proctitis; stricture/stenosis (including anastomotic):GI. Adverse events are graded using Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the adverse event (AE). The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to adverse event.	From the start of treatment to 90 days.
Secondary	Percentage of Patients With Any Grade 3+ Treatment-related Adverse Events	Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the adverse event (AE). The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.	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.
Secondary	Percentage of Patients With Any Late Grade 3+ Treatment-related Adverse Events	Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each adverse events (AE) based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. Late is defined as more than 90 days after the start of radiation therapy.	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.
Secondary	Percentage of Cervical Carcinoma Patients That Were Chemotherapy Compliant	Chemotherapy treatment was centrally reviewed for quality assurance and compliance once complete chemotherapy treatment data was received from sites.	From start to end of chemotherapy, approximately five weeks from registration.
Secondary	Rate of Local-regional Failure at Five Years	Local-regional failure time is defined as time from registration to date of local-regional failure (any failure in the treatment field, which will be the pelvis only), death without local-regional failure (competing risk), or last known follow-up (censored). Local-regional failure rates are estimated by the cumulative incidence method.	From registration to five years.
Secondary	Rate of Distant Metastases at Five Years	Distant Metastases failure time is defined as time from registration to date of distant disease, death without distant metastases (competing risk), or last known follow-up (censored) and is estimated by the cumulative incidence method. Para-aortic nodal disease is considered to be distant disease for a cervical primary, but not for an endometrial primary.	From registration to five years
Secondary	Rate of Disease-free Survival at Five Years	Disease-free survival time is defined as time from registration to date of failure (any tumor recurrence, development of distant metastases or death from any cause) and is estimated by the Kaplan-Meier method. Patients last known to be alive without failure are censored at the date of last contact.	From registration five years
Secondary	Rate of Overall Survival at Five Years	Overall survival time is defined as time from randomization to the date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.	From randomization to five years