Carboplatin and Paclitaxel With or Without Cisplatin and Radiation Therapy in Treating Patients With Stage I, Stage II, Stage III, or Stage IVA Endometrial Cancer

Tracking Information
First Submitted Date ICMJE	July 17, 2009
First Posted Date ICMJE	July 20, 2009
Last Update Posted Date	January 10, 2018
Actual Study Start Date ICMJE	June 29, 2009
Actual Primary Completion Date	March 9, 2017 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: December 23, 2014)	Recurrence-free survival (RFS) [ Time Frame: From study entry until disease recurrence, death, or date of last contact, assessed up to 8 years ]; Independence between the two endpoints, RFS and survival, and randomized treatment will be assessed with a stratified logrank test for an intent-to-treat analysis of eligible patients.
Original Primary Outcome Measures ICMJE; (submitted: July 17, 2009)	Recurrence-free survival
Change History	Complete list of historical versions of study NCT00942357 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: February 9, 2016)	Cumulative incidence of distant metastases (beyond the pelvis and vagina) [ Time Frame: Up to 8 years ]; Cumulative incidence of grade 3 or higher bowel-related gastrointestinal adverse events graded by the NCI CTCAE version 3.0 [ Time Frame: Up to 3 years ]The cumulative incidence of grade 3 or higher bowel-related gastrointestinal adverse events will also be estimated using the date of onset and will account for competing events of death, progression, and non-protocol cancer treatment.; Cumulative incidence of local recurrence (limited to the pelvis or vagina) [ Time Frame: Up to 8 years ]; Incidence of acute and adverse effects as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version (CTCAE) version 3.0 [ Time Frame: Up to completion of study treatment ]The maximum grade over the entire course of therapy for any individual effect will be used as a summary of acute toxicity. The Kruskal-Wallis test corrected for ties will be used to compare the maximum grade of acute adverse effects of therapy by treatment arm.; Incidence of late adverse events as graded by the NCI CTCAE version 3.0 [ Time Frame: Up to 3 years ]The maximum grade over the follow-up period (prior to initiation of subsequent therapy) for any individual effect will be used as summary of late adverse effects.; Overall survival [ Time Frame: From entry into the study to death or the date of last contact, assessed up to 8 years ]Independence between the two endpoints, RFS and survival, and randomized treatment will be assessed with a stratified logrank test for an intent-to-treat analysis of eligible patients.; Patient-reported quality of life (QOL) [ Time Frame: Up to 1 year after completion of study treatment ]QOL will be measured using the Functional Assessment of Cancer Therapy (FACT)-General, Physical Well-being (PWB) and Functional Well-being (FWB) subscales, FACT-Endometrial Cancer additional concerns subscale, FACT/GOG-Neurotoxicity (NTX)-4 subscale, and items C3 and C5 from the FACT-Colorectal. Linear mixed models adjusted for baseline score, age, and performance status at enrollment will be used to test the hypothesis of no difference in PWB+FWB scores and FACT-GOG/NTX-4 scores between assigned treatment arms in an intent-to-treat analysis of eligible patients.
Original Secondary Outcome Measures ICMJE; (submitted: July 17, 2009)	Overall survival; Cumulative incidence of local recurrence; Cumulative incidence of distant metastases; Acute and late adverse effects as measured by NCI CTCAE v3.0; Patient-reported quality of life
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Carboplatin and Paclitaxel With or Without Cisplatin and Radiation Therapy in Treating Patients With Stage I, Stage II, Stage III, or Stage IVA Endometrial Cancer
Official Title ICMJE	A Randomized Phase III Trial of Cisplatin and Tumor Volume Directed Irradiation Followed by Carboplatin and Paclitaxel vs. Carboplatin and Paclitaxel for Optimally Debulked, Advanced Endometrial Carcinoma
Brief Summary	This randomized phase III trial studies carboplatin and paclitaxel to see how well they work with or without cisplatin and radiation therapy in treating patients with stage I-IVA endometrial cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel, and 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy and radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether carboplatin and paclitaxel are more effective with or without cisplatin and radiation therapy in treating patients with endometrial cancer.
Detailed Description	PRIMARY OBJECTIVES: I. To determine if treatment with cisplatin and volume-directed radiation followed by carboplatin and paclitaxel for 4 cycles (experimental arm) reduces the rate of recurrence or death (i.e., increases recurrence-free survival) when compared to chemotherapy consisting of carboplatin and paclitaxel for 6 cycles (control arm) in patients with stages III-IVA endometrial carcinoma (< 2 cm residual disease) or patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage I or II serous (uterine papillary serous carcinoma [UPSC]) or clear cell endometrial carcinoma and positive cytology. SECONDARY OBJECTIVES: I. To determine if treatment with cisplatin and volume-directed radiation followed by carboplatin and paclitaxel for 4 cycles (experimental arm) reduces the rate of death (i.e., increases survival) when compared to chemotherapy consisting of carboplatin and paclitaxel for 6 cycles (control arm) in patients with stages III-IVA endometrial carcinoma (< 2 cm residual disease) or patients with FIGO 2009 stage I or II serous (UPSC) or clear cell endometrial carcinoma and positive cytology. II. To compare the regimens with respect to acute and late adverse effects of therapy. III. To determine the impact of patient-reported quality of life during and following treatment for up to 1 year with the two treatment regimens. TERTIARY OBJECTIVES: I. To bank formalin-fixed, paraffin-embedded (FFPE) tumor tissue and whole blood specimens for future research. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive cisplatin intravenously (IV) on days 1 and 29. Patients also undergo radiation therapy once daily (QD), 5 days a week, for 5-6 weeks. Some patients may then undergo brachytherapy over 2-3 weeks. Beginning within 8 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer
Intervention ICMJE	Drug: Carboplatin Given IV; Drug: Cisplatin Given IV; Radiation: Internal Radiation Therapy Undergo brachytherapy; Drug: Paclitaxel Given IV; Other: Quality-of-Life Assessment Ancillary studies Other Name: Quality of Life Assessment; Radiation: Radiation Therapy Undergo radiation therapy
Study Arms	Experimental: Arm I (cisplatin, radiation therapy, paclitaxel, carboplatin) Patients receive cisplatin IV on days 1 and 29. Patients also undergo radiation therapy QD, 5 days a week, for 5-6 weeks. Some patients may then undergo brachytherapy over 2-3 weeks. Beginning within 8 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Interventions: Drug: Carboplatin Drug: Cisplatin Radiation: Internal Radiation Therapy Drug: Paclitaxel Other: Quality-of-Life Assessment Radiation: Radiation Therapy; Active Comparator: Arm II (paclitaxel and carboplatin) Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Interventions: Drug: Carboplatin Drug: Paclitaxel Other: Quality-of-Life Assessment
Publications *	Not Provided
* 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	Active, not recruiting
Actual Enrollment ICMJE; (submitted: August 23, 2017)	807
Original Estimated Enrollment ICMJE; (submitted: July 17, 2009)	804
Study Completion Date	Not Provided
Actual Primary Completion Date	March 9, 2017 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: All patients with surgical stage III or IVA endometrial carcinoma per FIGO 2009 staging criteria including clear cell and serous papillary and undifferentiated carcinoma Surgical stage III disease includes those patients with positive adnexa, parametrial involvement, tumor invading the serosa, positive pelvic and/or para-aortic nodes, or vaginal involvement Surgical stage IVA patients with bladder or bowel mucosal involvement, but no spread outside the pelvis; Patients with FIGO 2009 surgical stage I or II endometrial clear cell or serous carcinoma and with positive peritoneal cytology; Surgery must have included a hysterectomy and bilateral salpingo-oophorectomy; pelvic lymph node sampling and para-aortic lymph node sampling are optional; Patients with a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2; White blood cell (WBC) >= 3,000/mcl; Absolute neutrophil count (ANC) >= 1,500/mcl; Platelet count >= 100,000/mcl; Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 2.5 x upper limit of normal (ULN); Alkaline phosphatase =< 2.5 times ULN; Bilirubin =< 1.5 times ULN; Creatinine =< institutional ULN; Patients who have met the pre-entry requirements; testing values/results must meet eligibility criteria; Patients who have signed an approved informed consent and authorization permitting release of personal health information; Entry into the study is limited to no more than 8 weeks from the date of surgery Exclusion Criteria: Patients with carcinosarcoma; Patients with recurrent endometrial cancer; Patients with residual tumor after surgery (any single site) exceeding 2 cm in maximum dimension; Patients who have had pelvic or abdominal radiation therapy; Patients with positive pelvic washings as the only extra-uterine disease are NOT eligible if the histology is other than clear cell or papillary serous carcinoma; Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of active malignancy within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy; Patients with a history of serious co-morbid illness or uncontrolled illnesses that would preclude protocol therapy; Patients with an estimated survival of less than three months; Patients with FIGO 2009 stage IVB endometrial cancer; Patients with parenchymal liver metastases; Patients who have received prior chemotherapy for endometrial cancer; Patients with a history of myocardial infarction, unstable angina, or uncontrolled arrhythmia within 3 months from enrollment
Sex/Gender	Sexes Eligible for Study: Female
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Canada, Korea, Republic of, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00942357
Other Study ID Numbers ICMJE	GOG-0258; NCI-2011-01951 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); CDR0000649079; GOG-0258 ( Other Identifier: NRG Oncology ); GOG-0258 ( Other Identifier: CTEP ); U10CA180868 ( U.S. NIH Grant/Contract ); U10CA027469 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Gynecologic Oncology Group
Study Sponsor ICMJE	Gynecologic Oncology Group
Collaborators ICMJE	National Cancer Institute (NCI)
Investigators ICMJE	Principal Investigator: Daniela Matei NRG Oncology
PRS Account	Gynecologic Oncology Group
Verification Date	August 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP