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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

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ClinicalTrials.gov Identifier: NCT00331760
Recruitment Status : Completed
First Posted : May 31, 2006
Results First Posted : June 3, 2013
Last Update Posted : February 26, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group

Tracking Information
First Submitted Date  ICMJE May 30, 2006
First Posted Date  ICMJE May 31, 2006
Results First Submitted Date  ICMJE April 12, 2013
Results First Posted Date  ICMJE June 3, 2013
Last Update Posted Date February 26, 2019
Study Start Date  ICMJE March 2006
Actual Primary Completion Date February 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 3, 2013)
Reproducibility of Radiation Technique (Number of Unacceptable Deviations in Central IMRT Quality Assurance Review) [ Time Frame: IMRT planning and dosing data is centrally reviewed for quality assurance after treatment delivery. ]
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%.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 1, 2019)
  • Percentage of Patients With Grade 2+ Bowel Adverse Events [ Time Frame: From the start of treatment to 90 days. ]
    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.
  • Percentage of Patients With Any Grade 3+ Treatment-related Adverse Events [ Time Frame: 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. ]
    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.
  • Percentage of Patients With Any Late Grade 3+ Treatment-related Adverse Events [ Time Frame: 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. ]
    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.
  • Percentage of Cervical Carcinoma Patients That Were Chemotherapy Compliant [ Time Frame: From start to end of chemotherapy, approximately five weeks from registration. ]
    Chemotherapy treatment was centrally reviewed for quality assurance and compliance once complete chemotherapy treatment data was received from sites.
  • Rate of Local-regional Failure at Five Years [ Time Frame: From registration to 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.
  • Rate of Distant Metastases at Five Years [ Time Frame: From registration to 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.
  • Rate of Disease-free Survival at Five Years [ Time Frame: From registration 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.
  • Rate of Overall Survival at Five Years [ Time Frame: From randomization to 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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE A Phase II Study of Intensity Modulated Radiation Therapy (IMRT) to the Pelvis ± Chemotherapy for Post-Operative Patients With Either Endometrial or Cervical Carcinoma
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cervical Cancer
  • Endometrial Cancer
Intervention  ICMJE
  • Drug: cisplatin
  • Radiation: intensity-modulated radiation therapy
Study Arms  ICMJE
  • Endometrial Cancer: IMRT
    Endometrial Cancer patients receive Intensity Modulated Radiation Therapy (IMRT) 28 fractions over 5.5 weeks.
    Intervention: Radiation: intensity-modulated radiation therapy
  • Cervical Cancer: IMRT + Chemotherapy (cisplatin)
    Cervical patients receive Intensity Modulated Radiation Therapy (IMRT) 28 fractions over 5.5 weeks and concurrent weekly cisplatin 40 mg/m^2 for five weeks.
    Interventions:
    • Drug: cisplatin
    • Radiation: intensity-modulated radiation therapy
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 12, 2013)
106
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE December 2016
Actual Primary Completion Date February 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00331760
Other Study ID Numbers  ICMJE RTOG-0418
CDR0000472905
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Radiation Therapy Oncology Group
Study Sponsor  ICMJE Radiation Therapy Oncology Group
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • NRG Oncology
Investigators  ICMJE
Study Chair: Anuja Jhingran, MD M.D. Anderson Cancer Center
PRS Account Radiation Therapy Oncology Group
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP