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

• ClinicalTrials.gov Identifier: NCT00942357
• Recruitment Status: Active, not recruiting
• First Posted: July 20, 2009
• Results First Posted: December 19, 2018
• Last Update Posted: October 19, 2021
• Sponsor: Gynecologic Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): GOG Foundation ( Gynecologic Oncology Group )

Tracking Information

• First Submitted Date: July 17, 2009
• First Posted Date: July 20, 2009
• Results First Submitted Date: August 23, 2018
• Results First Posted Date: December 19, 2018
• Last Update Posted Date: October 19, 2021
• Actual Study Start Date: June 29, 2009
• Actual Primary Completion Date: February 15, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 17, 2018)

Number of Participants With Recurrence, Progression or Death [ Time Frame: Disease was to be assessed at baseline, end of treatment and every 6 months for two years, and annually up to 5 years. ]

Number of participants enrolled with recurrence or progression of disease or death up to date of last contact. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion or the appearance of new lesions.

• Original Primary Outcome Measures (submitted: July 17, 2009): Recurrence-free survival

Current Secondary Outcome Measures (submitted: December 17, 2018)

• Number of Participants With Acute Adverse Effects as Graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version (CTCAE) Version 3.0 [ Time Frame: Assessed throughout the treatment period and for 21-30 days after discontinuation of treatment ]
  The maximum grade of all treatment emergent adverse events without regard to attribution. General guidelines for severity of adverse events are as follows: Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life threatening and Grade 5 is death.
• Number of Participants With Late Adverse Events as Graded by the NCI CTCAE Version 3.0 [ Time Frame: Assessed every 6 months for 3 years ]
  The maximum grade of Adverse events reported during follow-up until progression of disease, a change of therapy or otherwise off study for a maximum of 3 years without regard to attribution. General guidelines for severity of adverse events are as follows: Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life threatening and Grade 5 is death.
• 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 Peripheral Neuropathy Symptoms [ Time Frame: Prior to study treatment (baseline), Arm 1: 1 week post completion of radiation therapy, Arm 2: Prior to cycle 3 (6 weeks post starting of study treatment), 18 weeks post the starting of study treatement, 70 weeks post the starting of study treatment ]
  Patient reported peripheral neuropathy symptoms was measured with the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity subscale (short version) (FACT/GOG-Ntx subscale). The FACT/GOG-Ntx subscale contains 4 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative items, reversal was performed prior to score calculation. According to the FACIT measurement system, the Ntx score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the scale. The Ntx score ranges 0-16 with a large score suggests less peripheral neuropathy symptoms.
• Patient-reported Quality of Life (QOL) [ Time Frame: Prior to study treatment (baseline), Arm 1: 1 Week post completion of radiation therapy, Arm 2: Prior to cycle 3 (6 weeks post starting of study treatment), 18 weeks post the starting of study treatment, 70 weeks post the starting of study treatment ]
  Patient reported quality of life was measured with the Treatment Outcome Index of the Functional Assessment of Cancer Therapy for endometrial cancer (FACT-En TOI). It is a scale for assessing general QOL of endometrial cancer patients. It consists of three subscales: Physical Well Being (7 items), Functional Well Being (7 items), and Endometrium Cancer subscale (16 items). Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). According to the FACIT measurement system, a subscale score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the subscale. The FACT-En TOI score is calculated as the sum of the subscale scores, ranges are 0-120 with a large score suggesting a better QOL.

Original Secondary Outcome Measures (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 Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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: 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Endometrial Clear Cell Adenocarcinoma
• Endometrial Serous Adenocarcinoma
• Stage IA Uterine Corpus Cancer AJCC v7
• Stage IB Uterine Corpus Cancer AJCC v7
• Stage II Uterine Corpus Cancer AJCC v7
• Stage IIIA Uterine Corpus Cancer AJCC v7
• Stage IIIB Uterine Corpus Cancer AJCC v7
• Stage IIIC Uterine Corpus Cancer AJCC v7
• Stage IVA Uterine Corpus Cancer AJCC v7

Intervention

• Drug: Carboplatin
  Given IV
  Other Names:

  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
• Drug: Cisplatin
  Given IV
  Other Names:

  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
• Radiation: Internal Radiation Therapy
  Undergo brachytherapy
  Other Names:

  • BRACHYTHERAPY
  • internal radiation
  • Internal Radiation Brachytherapy
  • Radiation Brachytherapy
• Drug: Paclitaxel
  Given IV
  Other Names:

  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat
• Other: Quality-of-Life Assessment
  Ancillary studies
  Other Name: Quality of Life Assessment
• Radiation: Radiation Therapy
  Undergo radiation therapy
  Other Names:

  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • irradiation
  • Radiation
  • Radiotherapeutics
  • RADIOTHERAPY
  • RT
  • Therapy, Radiation

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 *

• Matulonis UA, Huang HQ, Filiaci VL, Randall M, DiSilvestro PA, Moxley KM, Fowler JM, Powell MA, Spirtos NM, Tewari KS, Richards WE, Nakayama JM, Mutch DG, Miller DS, Matei D, Wenzel LB. Patient reported outcomes for cisplatin and radiation followed by carboplatin/paclitaxel versus carboplatin/paclitaxel for locally advanced endometrial carcinoma: An NRG oncology study. Gynecol Oncol. 2022 Feb;164(2):428-436. doi: 10.1016/j.ygyno.2021.11.021. Epub 2021 Dec 11.
• Matei D, Filiaci V, Randall ME, Mutch D, Steinhoff MM, DiSilvestro PA, Moxley KM, Kim YM, Powell MA, O'Malley DM, Spirtos NM, Small W Jr, Tewari KS, Richards WE, Nakayama J, Matulonis UA, Huang HQ, Miller DS. Adjuvant Chemotherapy plus Radiation for Locally Advanced Endometrial Cancer. N Engl J Med. 2019 Jun 13;380(24):2317-2326. doi: 10.1056/NEJMoa1813181.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 17, 2018): 813
• Original Estimated Enrollment (submitted: July 17, 2009): 804
• Estimated Study Completion Date: July 28, 2024
• Actual Primary Completion Date: February 15, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Korea, Republic of, United States

Administrative Information

• NCT Number: NCT00942357
• Other Study ID Numbers: GOG-0258; NCI-2011-01951 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 10-00685; 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
• Current Responsible Party: GOG Foundation ( Gynecologic Oncology Group )
• Original Responsible Party: Philip J. DiSaia, Gynecologic Oncology Group
• Current Study Sponsor: Gynecologic Oncology Group
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Daniela E Matei; NRG Oncology

• PRS Account: GOG Foundation
• Verification Date: September 2021