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A Randomized Phase III Study of Standard vs. IMRT Pelvic Radiation for Post-Operative Treatment of Endometrial and Cervical Cancer (TIME-C)

Phase 3
18 Years
Open (Enrolling)
Cervical Cancer, Endometrial Cancer, Gastrointestinal Complications, Perioperative/Postoperative Complications, Radiation Toxicity, Urinary Complications, Urinary Tract Toxicity

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Trial Information

A Randomized Phase III Study of Standard vs. IMRT Pelvic Radiation for Post-Operative Treatment of Endometrial and Cervical Cancer (TIME-C)



- 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.


- 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

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.

Inclusion Criteria


- Pathologically proven diagnosis of endometrial or cervical cancer within 90 days of

- 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

- 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

- 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

- 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


- 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 ≤ 1.0 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

- 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)


- 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

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Acute gastrointestinal toxicity, as measured by bowel domain of EPIC, at 5 weeks from the start of pelvic radiation

Outcome Time Frame:

Week 5 of Radiation Therapy (RT)

Safety Issue:


Principal Investigator

Ann Klopp, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Federal Government

Study ID:

RTOG 1203



Start Date:

November 2012

Completion Date:

Related Keywords:

  • Cervical Cancer
  • Endometrial Cancer
  • Gastrointestinal Complications
  • Perioperative/Postoperative Complications
  • Radiation Toxicity
  • Urinary Complications
  • Urinary Tract Toxicity
  • gastrointestinal complications
  • perioperative/postoperative 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
  • Endometrial Neoplasms
  • Uterine Cervical Neoplasms
  • Postoperative Complications
  • Adenoma
  • Radiation Injuries



Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
Universtiy of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104