Standard Versus Intensity-Modulated Pelvic Radiation Therapy in Treating Patients With Endometrial or Cervical Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Radiation Therapy Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT01672892
First received: August 23, 2012
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

RATIONALE: Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.

PURPOSE: This randomized phase III trial is studying two different methods of radiation and their side effects and comparing how well they work in treating endometrial and cervical cancer after surgery.


Condition Intervention Phase
Cervical Cancer
Endometrial Cancer
Gastrointestinal Complications
Perioperative/Postoperative Complications
Radiation Toxicity
Urinary Complications
Urinary Tract Toxicity
Radiation: 3-dimensional conformal radiation therapy
Radiation: intensity-modulated radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase III Study of Standard vs. IMRT Pelvic Radiation for Post-Operative Treatment of Endometrial and Cervical Cancer (TIME-C)

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Acute gastrointestinal toxicity, as measured by bowel domain of EPIC, at 5 weeks from the start of pelvic radiation [ Time Frame: Week 5 of Radiation Therapy (RT) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Validation of EPIC Bowel and Urinary domains [ Time Frame: Before study start, Week 3 of RT, Week 5 of RT, 4-6 Weeks after RT, 1 year from start of RT and 3 years from start of RT ] [ Designated as safety issue: No ]
  • Toxicity, as measured by CTCAE v. 4.0 [ Time Frame: Before study start, Week 5 of RT, 4-6 Weeks after RT, 1 year from start of RT and 3 years from start of RT ] [ Designated as safety issue: Yes ]
  • Urinary toxicity, as measured by EPIC urinary domain [ Time Frame: Before study start, Week 3 of RT, Week 5 of RT, 4-6 Weeks after RT, 1 year from start of RT and 3 years from start of RT ] [ Designated as safety issue: Yes ]
  • Quality of life, as measured by the FACT-G with cervix subscale [ Time Frame: Before study start, Week 5 of RT, 4-6 Weeks after RT, 1 year from start of RT and 3 years from start of RT ] [ Designated as safety issue: No ]
  • Health utilities, as measured by EQ-5D [ Time Frame: Before study start, Week 5 of RT, 4-6 Weeks after RT, 1 year from start of RT and 3 years from start of RT ] [ Designated as safety issue: No ]
  • Local-regional control [ Time Frame: End of Study ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: End of Study ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: End of Study ] [ Designated as safety issue: No ]
  • Identification of molecular predictors of radiation toxicity and novel circulating cancer biomarkers [ Time Frame: End of Study ] [ Designated as safety issue: No ]

Estimated Enrollment: 281
Study Start Date: November 2012
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I
Patients undergo standard (3-dimensional) radiation therapy 5 days a week for up to 5.5 weeks.
Radiation: 3-dimensional conformal radiation therapy
Undergo radiation therapy
Experimental: Arm II
Patients undergo intensity-modulated radiation therapy (IMRT) 5 days a week for up to 5.5 weeks.
Radiation: intensity-modulated radiation therapy
Undergo radiation therapy

Detailed Description:

OBJECTIVES:

Primary

  • To determine if pelvic intensity-modulated radiation therapy (IMRT) reduces acute gastrointestinal toxicity in the 5th week (after 23-25 fractions) of pelvic radiation as measured with the expanded prostate cancer index composite (EPIC) instrument.

Secondary

  • To determine if grade 2+ gastrointestinal toxicity (Common Terminology Criteria for Adverse Events version 4.0 [CTCAE v. 4.0]) is reduced with IMRT compared to conventional whole-pelvis radiation therapy (WPRT).
  • To determine if grade 2+ hematologic toxicity (CTCAE v. 4.0) is reduced with IMRT compared to conventional WPRT.
  • To determine if urinary toxicity is reduced with IMRT using the EPIC urinary domain.
  • To validate EPIC bowel and urinary domains in women undergoing either IMRT pelvic radiation treatment or four-field pelvic radiation treatment for endometrial or cervical cancer.
  • To assess the impact of pelvic IMRT on quality of life using the Functional Assessment of Cancer Therapy-General (FACT-G) with cervix subscale.
  • To determine if there is any difference in local-regional control, disease-free survival, and overall survival between patients treated with IMRT as compared to conventional WPRT.
  • To perform a health-utilities analysis to measure the financial impact of pelvic IMRT via the EQ-5D instrument.
  • To identify molecular predictors of radiation toxicity and novel circulating cancer biomarkers.

OUTLINE: This is a multicenter study. Patients are stratified according to type of cancer (endometrial vs cervical), chemotherapy (none vs 5 courses of weekly cisplatin at 40 mg/m²), and radiation dose (45 Gy vs 50.4 Gy). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo standard (3-dimensional) radiation therapy 5 days a week for up to 5-6 weeks.
  • Arm II: Patients undergo intensity-modulated radiation therapy (IMRT) 5 days a week for up to 5-6 weeks.

Some patients receive cisplatin IV over 1 hour on day 1. Treatment continues weekly for 5 weeks, concurrently with radiation therapy, in the absence of unacceptable toxicity or disease progression.

Tissue and blood samples may be collected for biomarker and correlative analysis.

Quality of life may be assessed by questionnaires (including the Expanded Prostate Cancer Index Composite [EPIC], the Functional Assessment of Cancer Therapy-General [FACT-G, Version 4], the EQ-5D, and the Common Toxicity Criteria Adverse Events - Patient-Reported Outcome [PRO-CTCAE]) instruments at baseline and periodically during and after study therapy.

After completion of study therapy, patients are followed every 6 months for the first 2 years and then annually for 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Pathologically proven diagnosis of endometrial or cervical cancer within 90 days of registration
  • Patients must have undergone a hysterectomy (total abdominal hysterectomy, vaginal hysterectomy or radical hysterectomy, or total laparoscopic hysterectomy) for carcinoma of the cervix or endometrium within 49 days prior to registration

    • Performance of a bilateral salpingo-oophorectomy will be at the treating surgeon's discretion
    • No positive or close (< 3 mm) resection margins
  • Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:

    • History/physical examination within 45 days prior to registration
    • Computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)-CT including the abdomen and pelvis should be performed for initial radiological staging (performed pre- or post-surgery within 90 days prior to registration)

      • Imaging performed postoperatively should show no evidence of residual disease
      • Any evidence of malignancy identified on preoperative imaging should have been completely resected surgically prior to protocol treatment
    • Chest x-ray or chest CT must be performed within 90 days prior to registration (unless a PET-CT has been performed)
  • Endometrial cancer:

    • Patients with the following histologic features are eligible for pelvic radiation therapy without weekly cisplatin:

      • Less than 50% myometrial invasion, grade 3 adenocarcinoma without uterine serous carcinoma (USC), or clear cell histology
      • At least 50% myometrial invasion, grade 1-2 adenocarcinoma without USC, or clear cell histology
    • Patients with the following histologic features may be treated with pelvic radiation with or without weekly cisplatin (the decision to add weekly cisplatin for these patients is at the treating physician's discretion):

      • At least 50% myometrial invasion, grade 3 including USC and clear cell carcinoma
      • International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrial cancer of any grade including USC and clear cell carcinoma
      • FIGO 2009 stage IIIC1 (pelvic lymph node positive only, para-aortic nodes sampled and negative) including USC and clear cell carcinoma
  • Cervical cancer:

    • Patients with the following pathology findings may be treated with pelvic radiation with or without weekly cisplatin at the treating physician's discretion:

      • Patients with intermediate-risk features including two of the following histologic findings after radical hysterectomy: 1/3 or more stromal invasion, lymph-vascular space invasion or large clinical tumor diameter (> 4 cm)
      • Patients with cervical cancer treated with a simple hysterectomy with negative margins
    • Patients with any of the following criteria following radical hysterectomy are eligible for this study and must receive weekly cisplatin:

      • Positive resected pelvic nodes (para-aortic nodes sampled and negative)
      • Microscopic parametrial invasion with negative margins
  • No patients with para-aortic nodal disease or who require extended-field radiotherapy beyond the pelvis
  • No patients with histology consisting of endometrial stromal sarcoma, leiomyosarcoma, malignant mixed mullerian tumor (MMMT), or carcinosarcoma
  • No evidence of metastatic disease outside of the pelvis

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-2
  • Absolute neutrophil count (ANC) ≥ 1,500 cells/mm³
  • Platelets ≥ 100,000 cells/mm³
  • Hemoglobin (Hgb) ≥ 8.0 g/dL (the use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable)
  • For patients receiving chemotherapy:

    • Within 14 days prior to registration, serum creatinine ≤ 1.5 mg/dL AND calculated creatinine clearance ≥ 50 mL/min
    • Aspartate aminotransferase (AST) ≤ 2 times upper limit of normal (ULN)
    • Bilirubin ≤ 2 times ULN
    • Alkaline phosphatase, magnesium, blood urea nitrogen (BUN), and electrolytes must be obtained and recorded
  • Fertile patients must use effective contraception
  • Not pregnant and/or breastfeeding
  • Willing and able to complete the bowel and urinary domains of the expanded prostate cancer index composite (EPIC) instrument prior to registration
  • No patients who exceed the weight/size limits of the treatment table or CT scanner
  • No mental status changes or bladder control problems that make the patient unable to comply with bladder-filling instructions
  • No prior invasive malignancy (except non-melanomatous skin cancer) unless disease-free for a minimum of 3 years
  • No patients with active inflammatory bowel disease
  • No severe, active co-morbidity, defined as follows:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    • Transmural myocardial infarction within the last 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    • Other major medical illness that requires hospitalization or precludes study therapy at the time of registration
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects (however, laboratory test coagulation parameters are not required for entry into this protocol)
    • Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition (however, human immunodeficiency virus [HIV] testing is not required for entry into this protocol)

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior radiation therapy to the pelvis
  • No prior treatment with platinum-based chemotherapy
  • Patients may NOT receive amifostine or other protective reagents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01672892

  Show 139 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Principal Investigator: Ann Klopp, MD, PhD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT01672892     History of Changes
Other Study ID Numbers: RTOG 1203, CDR0000738944, NCI-2012-02001
Study First Received: August 23, 2012
Last Updated: August 4, 2014
Health Authority: United States: Federal Government

Keywords provided by Radiation Therapy Oncology Group:
perioperative/postoperative complications
gastrointestinal complications
radiation toxicity
urinary complications
urinary tract toxicity
endometrial clear cell carcinoma
endometrial papillary serous carcinoma
stage IA endometrial carcinoma
stage IB endometrial carcinoma
stage II endometrial carcinoma
stage IIIA endometrial carcinoma
stage IIIB endometrial carcinoma
stage IIIC endometrial carcinoma
endometrial adenocarcinoma
cervical adenocarcinoma
stage IB cervical cancer
stage IIA cervical cancer
stage IIB cervical cancer

Additional relevant MeSH terms:
Postoperative Complications
Uterine Cervical Neoplasms
Radiation Injuries
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Wounds and Injuries
Pathologic Processes

ClinicalTrials.gov processed this record on September 16, 2014