Standard Versus Intensity-Modulated Pelvic Radiation Therapy in Treating Patients With Endometrial or Cervical Cancer
Condition: Cervical Cancer; Endometrial Cancer; Gastrointestinal Complications; Perioperative/Postoperative Complications; Radiation Toxicity; Urinary Complications; Urinary Tract Toxicity
MeSH terms: Uterine Cervical Neoplasms; Endometrial Neoplasms; Postoperative Complications
Intervention: Standard radiation therapy; intensity-modulated radiation therapy
Intervention description: Patients treated once a day, 5 days a week with a daily fraction size of 1.8 Gy. Whole pelvis treated with a four-field technique (AP/PA/R lateral/L lateral) to 45 or 50.4 Gy at 1.8 Gy/fraction. The dose is prescribed to the isocenter which is defined as the intersection of the four beams and can be normalized to an isodose line between 97-100%. The decision to deliver 45 or 50.4 Gy is at the physician's discretion and must be reported at the time of enrollment.; Patients treated once a day, 5 days a week with a daily fraction size of 1.8 Gy. All targets treated simultaneously. The vaginal planning target volume (PTV) (ITV with 7.0 mm margin) and nodal PTV receives 45 Gy in 25 fractions or 50.4 Gy in 28 fractions. The decision to deliver 45 or 50.4 Gy is at the physician's discretion and must be reported at the time of enrollment.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 289.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 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

Summary:

      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.
    

Eligibility criteria:

        Inclusion criteria:

          1. Pathologically proven diagnosis of endometrial or cervical cancer.

          2. 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 salpingooophorectomy will be at the treating surgeon's discretion.

          3. Appropriate stage for protocol entry, including no distant metastases, based upon the
             following minimum diagnostic workup:

               -  3.1 History/physical examination within 45 days prior to registration;

               -  3.2 CT, MRI or positron emission tomography - computed tomography (PET-CT)
                  including the abdomen and pelvis should be performed for initial radiological
                  staging. This may be performed pre- or post-surgery within 90 days prior to
                  registration. Imaging performed post-operatively should show no evidence of
                  residual disease. Any evidence of malignancy identified on pre-operative imaging
                  should have been completely resected surgically prior to protocol treatment.

               -  3.3 Chest CT or chest x-ray must be performed within 90 days prior to
                  registration (unless a PET-CT has been performed)

          4. Zubrod Performance Status 0-2

          5. Age ≥ 18;

          6. Complete blood count (CBC)/differential obtained within 14 days prior to registration
             on study, with adequate bone marrow function defined as follows:

               -  6.1 Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;

               -  6.2 Platelets ≥ 100,000 cells/mm3;

               -  6.3 Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to
                  achieve Hgb ≥ 8.0 g/dl is acceptable.)

          7. For patients receiving chemotherapy:

        7.1 Within 14 days prior to registration, serum creatinine ≤ 1.5 mg/dL and calculated
        creatinine clearance ≥ 50 cc/min. Both tests must be within these limits. The creatinine
        clearance should be calculated using the Cockcroft-Gault formula: (See Section 7.3.1) 7.2
        Aspartate aminotransferase (AST) ≤ 2 x upper limit of normal (ULN) 7.3 Bilirubin ≤ 2 x ULN
        7.4 Alkaline phosphatase, Mg, blood urea nitrogen (BUN) and electrolytes must be obtained
        and recorded 8 Endometrial Cancer: 8.1 Patients with the following histologic features are
        eligible for pelvic radiation therapy without weekly cisplatin:

          -  <50% myometrial invasion, grade 3 adenocarcinoma without uterine serous carcinoma
             (USC) or clear cell histology

          -  ≥50% myometrial invasion grade 1-2 adenocarcinoma without USC or clear cell histology
             8.2 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:

          -  ≥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 IIIC1 (pelvic lymph node positive only, para-aortic nodes negative if
             removed) including USC and clear cell carcinoma. Note: If para-aortic nodes are not
             removed, CT abdomen or PET CT must demonstrate no evidence of lymphadenopathy. 9.
             Cervical Cancer: 9.1 Patients with the following pathology findings may be treated
             with pelvic radiation with or without weekly cisplatin at the treating physician's
             discretion. The decision to add weekly cisplatin for these patients is at the treating
             physician's discretion. 9.1.1 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

          -  Large clinical tumor diameter (> 4 cm) 9.1.2 Patients with cervical cancer treated
             with a simple hysterectomy with negative margins 9.2 Patients with any of the
             following criteria following radical hysterectomy are eligible for this study and must
             receive weekly cisplatin:

          -  Positive resected pelvic nodes and para-aortic nodes negative if removed. Note: If
             para-aortic nodes are not removed, CT abdomen or PET CT must demonstrate no evidence
             of lymphadenopathy.

          -  Microscopic parametrial invasion with negative margins. 10. Patient must provide study
             specific informed consent prior to study entry. 11. Willingness and ability to
             complete the bowel and urinary domains of the EPIC prior to registration

        Exclusion criteria:

          1. Patients with para-aortic nodal disease or who require extended field radiotherapy
             beyond the pelvis.

          2. Patients with histology consisting of endometrial stromal sarcoma, leiomyosarcoma or
             malignant mixed mullerian mixed tumor (MMMT or carcinosarcoma)

          3. Patients who exceed the weight/size limits of the treatment table or CT scanner.

          4. Mental status changes or bladder control problems that make the patient unable to
             comply with bladder-filling instructions.

          5. Patients with evidence of metastatic disease outside of the pelvis.

          6. Patients with positive or close (< 3 mm) resection margins

          7. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
             for a minimum of 3 years.

          8. Prior radiation therapy to the pelvis

          9. Patients with active inflammatory bowel disease. 10 Severe, active co-morbidity,
             defined as follows:

               -  10.1 Unstable angina and/or congestive heart failure requiring hospitalization
                  within the last 6 months

               -  10.2 Transmural myocardial infarction within the last 6 months

               -  10.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the
                  time of registration

               -  10.4 Other major medical illness which requires hospitalization or precludes
                  study therapy at the time of registration

               -  10.5 Hepatic insufficiency resulting in clinical jaundice and/or coagulation
                  defects; note, however,that laboratory test coagulation parameters are not
                  required for entry into this protocol

               -  10.6 Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for
                  Disease Control and Prevention (CDC) definition; note, however, that HIV testing
                  is not required for entry into this protocol. The need to exclude patients with
                  AIDS from this protocol is necessary because the treatments involved in this
                  protocol may be significantly immunosuppressive. Protocol-specific requirements
                  may also exclude immunocompromised patients.

        11. Patients with prior treatment with platinum-based chemotherapy 12. Women who are
        breastfeeding