Radiation Therapy With or Without Cisplatin in Treating Patients With Recurrent Endometrial Cancer

Study Overview
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Brief Summary
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This randomized phase II trial studies radiation therapy and cisplatin to see how well they work compared with radiation therapy alone in treating patients with endometrial cancer that has come back. Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving radiation therapy together with cisplatin is more effective than radiation therapy alone in treating patients with endometrial cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To assess whether pelvic radiation therapy with concurrent cisplatin is more promising with respect to progression-free survival than pelvic radiation therapy alone in the treatment of recurrent uterine carcinoma limited to the pelvis and vagina. SECONDARY OBJECTIVES: I. To capture the sites of recurrence subsequent to treatment with pelvic radiation with or without concurrent weekly cisplatin in women with recurrent uterine carcinoma. II. To estimate overall survival of patients with recurrent uterine carcinoma treated with pelvic radiation therapy with or without concurrent weekly cisplatin. III. To estimate the prognostic significance of the location (central pelvis versus vagina) and size of the recurrence, in addition to the prognostic significance in the salvage setting of the histological subtype, grade, patient age, race, performance status, and the presence of lymph-vascular space involvement of the original tumor at the time of initial hysterectomy. IV. To evaluate toxicity derived from the combined cisplatin and radiation compared with radiation alone in this patient population. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo external-beam radiotherapy (EBRT) to the pelvis daily on days 1-5 for 5 weeks. After completion of EBRT, patients undergo intracavitary low-dose rate or high-dose rate brachytherapy* or low-dose rate interstitial brachytherapy*. ARM II: Patients undergo EBRT as in Arm I and receive cisplatin intravenously (IV) over 1-2 hours on days 1, 8, 15, 22, and 29. Patients then undergo brachytherapy* as in Arm I. NOTE: *IMRT boost is allowed for patients who are not candidates for brachytherapy. IMRT may also be used for the entire course of therapy for the treatment of the whole pelvis and/or the boost in patients not undergoing brachytherapy. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every month for 3 months, 3 months for 2 years and then every 6 months for 3 years.

Official Title
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A Randomized Trial of Pelvic Irradiation With or Without Concurrent Weekly Cisplatin in Patients With Pelvic-Only Recurrence of Carcinoma of the Uterine Corpus

Conditions
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Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation, Endometrial Mucinous Adenocarcinoma, Endometrial Squamous Cell Carcinoma, Recurrent Endometrial Clear Cell Adenocarcinoma, Recurrent Endometrial Endometrioid Adenocarcinoma, Recurrent Endometrial Serous Adenocarcinoma, Recurrent Endometrial Undifferentiated Carcinoma, Recurrent Uterine Corpus Cancer

Intervention / Treatment
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* Radiation: 3-Dimensional Conformal Radiation Therapy
* Drug: Cisplatin
* Radiation: Intensity-Modulated Radiation Therapy
* Radiation: Internal Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients must have undergone complete hysterectomy and bilateral salpingo-oophorectomy at the time of original therapy for their uterine carcinoma Patients must have a biopsy with histologically confirmed diagnosis of recurrent endometrial cancer confined to the pelvis and/or vagina and no evidence of extrapelvic disease Patients must have endometrial carcinoma including endometrioid adenocarcinoma, adenocarcinoma with squamous differentiation, mucinous adenocarcinoma, squamous cell carcinoma, mixed carcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, and serous adenocarcinoma histologies Patients must have no evidence of extrapelvic disease; complete workup staging should be performed prior to initiation of therapy to rule-out presence of metastatic disease; this should include: computed tomography (CT) scan of the thorax with IV contrast, as well as a CT of the pelvis and abdomen with IV and oral (PO) contrast performed using multi-detector CT and equal or less than 5 mm slice thickness; if the patient is unable to tolerate contrast, then magnetic resonance imaging (MRI) with IV gadolinium should be performed; a chest x-ray should be done first, and if abnormal, then a CT scan of the chest should be done Primary surgical debulking before protocol therapy is permissible; this would include removal of gross symptomatic disease in the pelvis and/or vagina Exenterative surgery is not permissible; patients with complete resection of gross recurrent disease are eligible Patients may have received prior hormone therapy and/or systemic chemotherapy; such therapy must have been completed at least 6 months prior to study entry and the patient has clear evidence of disease subsequent to such therapy; patients must not have received neoadjuvant chemotherapy for the present recurrent disease Patients must have Gynecologic Oncology Group (GOG) performance status 0, 1, or 2 Patients must have an estimated survival greater or equal to 3 months Absolute neutrophil count (ANC) >= 1,500/mm^3 , equivalent to Common Toxicity Criteria (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 3.0) grade 1 Platelets >= 100,000/mm^3 (CTCAE v 3.0 grade 0-1) Creatinine =< institutional upper limit normal (ULN), CTCAE v 3.0 grade 0; NOTE: if creatinine > ULN, creatinine clearance must be > 50 mL/min Bilirubin =< 1.5 x ULN (CTCAE v 3.0 grade 1) Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 x ULN (CTCAE v 3.0 grade 0-1) Alkaline phosphatase =< 2.5 x ULN (CTCAE v 3.0 grade 0-1) Neuropathy (sensory and motor) =< CTCAE v 3.0 grade 1 Patients with ureteral obstruction must undergo stent or nephrostomy tube placement prior to study entry Patients who have met the pre-entry requirements Patients must have signed an approved informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization Exclusion Criteria: Patients with evidence of disease outside of the pelvis, including presence of positive periaortic or inguino-femoral nodes Patients who have received previous vaginal, pelvic, or abdominal irradiation Patients who received chemotherapy directed at the present recurrence Patients with septicemia or severe infection Patients who have circumstances that will not permit completion of this study or the required follow-up Patients with renal abnormalities, such as pelvic kidney, horseshoe kidney, or renal transplantation, that would require modification of radiation fields Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy Patients who have undergone complete surgical resection of the recurrent tumor and have no evidence of residual disease evaluable clinically and by CT or MRI imaging, following resection Patients who have a significant history of cardiac disease, i.e., uncontrolled hypertension, unstable angina, congestive heart failure, or uncontrolled arrhythmias within 6 months of registration Patients with history of active collagen vascular disease Patients with GOG performance grade of 3 or 4
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (brachytherapy, radiation therapy)<br>Patients undergo EBRT to the pelvis daily on days 1-5 for 5 weeks. After completion of EBRT, patients undergo intracavitary low-dose rate or high-dose rate brachytherapy or low-dose rate interstitial brachytherapy. | Radiation: 3-Dimensional Conformal Radiation Therapy<br>* Undergo 3-dimensional conformal radiation therapy<br>* Other names: Radiation, 3D Conformal;Radiation: Intensity-Modulated Radiation Therapy<br>* Undergo IMRT<br>* Other names: Radiation, Intensity-Modulated Radiotherapy;Radiation: Internal Radiation Therapy<br>* Given intracavitarily or interstitially<br>* Other names: Radiation, Internal;|
| Experimental: Arm II (brachytherapy, radiation therapy, cisplatin)<br>Patients undergo EBRT as in Arm I and receive cisplatin IV over 1-2 hours on days 1, 8, 15, 22, and 29. Patients then undergo brachytherapy as in Arm I. | Radiation: 3-Dimensional Conformal Radiation Therapy<br>* Undergo 3-dimensional conformal radiation therapy<br>* Other names: Radiation, 3D Conformal;Drug: Cisplatin<br>* Given IV<br>* Other names: Platosin;Radiation: Intensity-Modulated Radiation Therapy<br>* Undergo IMRT<br>* Other names: Radiation, Intensity-Modulated Radiotherapy;Radiation: Internal Radiation Therapy<br>* Given intracavitarily or interstitially<br>* Other names: Radiation, Internal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Disease Progression or Death. | The number of participants with disease progression or death from study entry to progression or death. Participants who experienced progression or death were reported by treatment arm. | Median follow-up for progression-free survival was 62 months with a maximum of 128 months. Patients were followed from study entry until disease progression, death, or date of last contact | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants That Experienced Death on Study | Overall survival is the period from study entry until death or date of last contact. The treatment regimens were compared with regard to overall survival. | Participants were followed from study entry until death or date of last contact. Median follow-up for overall survival was 62 months with a maximum of 128 months. | 
| Number of Participants in Select Prognostic Groups Who Experienced Progression or Death on Study. | Participants were put in prognostic groups including baseline factors of tumor location (vagina only vs. all others) and histology (serious and clear cell vs. all others). They were assessed for prognostic associations with progression-free survival. Participant factors were collected at baseline. Participants were followed from study entry until disease progression, death, or date of last contact for progression-free survival. | Median follow-up for progression-free survival was 62 months with a maximum of 128 months. | 
| Number of Participants That Experienced Adverse Effects Grade 3 or Higher | Number of treated participants with adverse events of grade 3 or higher. Graded by Common Terminology Criteria for Adverse Events version 3.0. Treated patients were evaluated for adverse events during the treatment period, every month for the first three months after completion of therapy up to 2 years, and then every six months for the next 3 years. | Maximum follow-up for adverse events was 61 months. |