Paclitaxel and Carboplatin or Ifosfamide in Treating Patients With Newly Diagnosed, Persistent or Recurrent Uterine, Ovarian, Fallopian Tube, or Peritoneal Cavity Cancer

• ClinicalTrials.gov Identifier: NCT00954174
• Recruitment Status: Active, not recruiting
• First Posted: August 7, 2009
• Results First Posted: August 10, 2020
• Last Update Posted: September 30, 2021
• Sponsor: GOG Foundation
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): GOG Foundation

Tracking Information

• First Submitted Date: August 6, 2009
• First Posted Date: August 7, 2009
• Results First Submitted Date: March 13, 2020
• Results First Posted Date: August 10, 2020
• Last Update Posted Date: September 30, 2021
• Actual Study Start Date: August 17, 2009
• Actual Primary Completion Date: March 30, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 27, 2020)

Overall Survival [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 115 months. ]

Measured in months from randomization to last contact or death. Primary analysis was restricted to the eligible uterine carcinosarcoma cohort.

• Original Primary Outcome Measures (submitted: August 6, 2009): Duration of overall survival

Current Secondary Outcome Measures (submitted: July 27, 2020)

• Duration of Progression-free Survival [ Time Frame: Approximately 9 years and 7 months ]
  Measured in months from randomization to last contact or the earlier of the date of progression or death.
• Incidence of Adverse Events as Assessed by CTCAE Version 3.0 [ Time Frame: Patients were assessed for adverse events during active protocol treatment and up to 30 days after the last cycle of treatment on the protocol. ]
  Maximum grade experienced among all treated and eligible patients. The grades are described by severity. Grade 1 is the lowest (most mild) and Grade 5 being death (most severe). Adverse events were analyzed across cohorts since disease site was considered independent of AEs.
• Patient-Reported Quality of Life (QOL) - Baseline [ Time Frame: Baseline - Prior to study treatment ]
  Patient reported quality of life was measured with the Treatment Outcome Index (TOI) of the Functional Assessment of Cancer Therapy for endometrial cancer (FACT-En TOI). The FACT-En TOI is a scale for assessing general QOL of endometrial cancer patients. The FACT-En TOI score ranges 0-120 with a large score suggesting better QOL. Quality of Life was analyzed across cohorts since disease site was considered independent of Quality of Life.
• Patient Reported Quality of Life (QOL) - Post Baseline [ Time Frame: Prior to cycle 3, Prior to cycle 6, 30 weeks post cycle 1. ]
  Patient reported quality of life was measured with the Treatment Outcome Index (TOI) of the Functional Assessment of Cancer Therapy for endometrial cancer (FACT-En TOI). The FACT-En TOI is a scale for assessing general QOL of endometrial cancer patients. The FACT-En TOI score ranges 0-120 with a large score suggesting better QOL. Quality of Life was analyzed across cohorts since disease site was considered independent of Quality of Life.
• Patient Reported Peripheral Neuropathy Symptoms - Baseline [ Time Frame: Baseline (Pre cycle 1) ]
  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 11 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). . The Ntx score ranges 0-44 with a large score suggesting less peripheral neuropathy symptoms. Quality of Life was analyzed across cohorts since disease site was considered independent of Quality of Life.
• Patient-reported Peripheral Neuropathy Symptoms - Post Baseline [ Time Frame: Prior to cycle 3, Prior to cycle 6, 30 weeks post cycle 1 ]
  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 11 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). The Ntx score ranges 0-44 with a large score suggesting less peripheral neuropathy symptoms.Quality of Life was analyzed across cohorts since disease site was considered independent of Quality of Life.

Original Secondary Outcome Measures (submitted: August 6, 2009)

• Duration of progression-free survival
• Toxicity as assessed by CTCAE version 3.0
• Quality of life

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Paclitaxel and Carboplatin or Ifosfamide in Treating Patients With Newly Diagnosed, Persistent or Recurrent Uterine, Ovarian, Fallopian Tube, or Peritoneal Cavity Cancer
• Official Title: A Randomized Phase III Trial of Paclitaxel Plus Carboplatin Versus Ifosfamide Plus Paclitaxel in Chemotherapy-Naive Patients With Newly Diagnosed Stage I-IV, Persistent or Recurrent Carcinosarcoma (Mixed Mesodermal Tumors) of the Uterus, Fallopian Tube, Peritoneum or Ovary
• Brief Summary: This randomized phase III trial studies paclitaxel and carboplatin see how well they work compared with paclitaxel and ifosfamide in treating patients with fallopian tube, or peritoneal cavity cancer that is newly diagnosed, persistent, or has come back (recurrent). Drugs used in chemotherapy, such as paclitaxel, carboplatin, and ifosfamide, 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 paclitaxel is more effective when given with carboplatin or ifosfamide in treating patients with uterine, ovarian, fallopian tube, or peritoneal cavity cancer.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine if treatment with combination paclitaxel and carboplatin (TC) chemotherapy does not result in an inferior death rate when compared to ifosfamide, mesna, and paclitaxel chemotherapy.

SECONDARY OBJECTIVES:

I. To determine if treatment with combination paclitaxel and carboplatin (TC) chemotherapy does not result in an inferior progression-free survival when compared to ifosfamide, mesna, and paclitaxel chemotherapy.

II. To determine if acute toxicity, specifically physician-assessed neurotoxicity and infection, associated with combination paclitaxel and carboplatin chemotherapy is reduced compared to that of ifosfamide, mesna, and paclitaxel chemotherapy.

III. To determine if treatment with combination paclitaxel and carboplatin chemotherapy is associated with superior patient-reported quality of life and neurotoxicity scores compared to that of ifosfamide, mesna, and paclitaxel chemotherapy.

TERTIARY OBJECTIVES:

I. To bank formalin-fixed, paraffin-embedded (FFPE) tumor tissue and deoxyribonucleic acid (DNA) extracted from whole blood for future research.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours followed by carboplatin IV over 30-60 minutes on day 1.

ARM II: Patients receive ifosfamide IV over 1 hour on days 1-3 followed by paclitaxel as in Arm I.

In both arms, treatment repeats every 21 days for 6-10 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, 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

• Mixed Mesodermal (Mullerian) Tumor
• Ovarian Carcinosarcoma
• Recurrent Fallopian Tube Carcinoma
• Recurrent Ovarian Carcinoma
• Recurrent Primary Peritoneal Carcinoma
• Stage I Ovarian Cancer AJCC v6 and v7
• Stage IA Fallopian Tube Cancer AJCC v6 and v7
• Stage IA Ovarian Cancer AJCC v6 and v7
• Stage IA Uterine Sarcoma AJCC v7
• Stage IB Fallopian Tube Cancer AJCC v6 and v7
• Stage IB Ovarian Cancer AJCC v6 and v7
• Stage IB Uterine Sarcoma AJCC v7
• Stage IC Fallopian Tube Cancer AJCC v6 and v7
• Stage IC Ovarian Cancer AJCC v6 and v7
• Stage IC Uterine Sarcoma AJCC v7
• Stage II Ovarian Cancer AJCC v6 and v7
• Stage IIA Fallopian Tube Cancer AJCC v6 and v7
• Stage IIA Ovarian Cancer AJCC V6 and v7
• Stage IIA Uterine Sarcoma AJCC v7
• Stage IIB Fallopian Tube Cancer AJCC v6 and v7
• Stage IIB Ovarian Cancer AJCC v6 and v7
• Stage IIB Uterine Sarcoma AJCC v7
• Stage IIC Fallopian Tube Cancer AJCC v6 and v7
• Stage IIC Ovarian Cancer AJCC v6 and v7
• Stage IIIA Fallopian Tube Cancer AJCC v7
• Stage IIIA Ovarian Cancer AJCC v6 and v7
• Stage IIIA Primary Peritoneal Cancer AJCC v7
• Stage IIIA Uterine Sarcoma AJCC v7
• Stage IIIB Fallopian Tube Cancer AJCC v7
• Stage IIIB Ovarian Cancer AJCC v6 and v7
• Stage IIIB Primary Peritoneal Cancer AJCC v7
• Stage IIIB Uterine Sarcoma AJCC v7
• Stage IIIC Fallopian Tube Cancer AJCC v7
• Stage IIIC Ovarian Cancer AJCC v6 and v7
• Stage IIIC Primary Peritoneal Cancer AJCC v7
• Stage IIIC Uterine Sarcoma AJCC v7
• Stage IV Fallopian Tube Cancer AJCC v6 and v7
• Stage IV Ovarian Cancer AJCC v6 and v7
• Stage IV Primary Peritoneal Cancer AJCC v7
• Stage IVA Uterine Sarcoma AJCC v7
• Stage IVB Uterine Sarcoma AJCC v7
• Uterine Carcinosarcoma

Intervention

• Drug: Carboplatin
  Given IV
  Other Names:

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

  • Asta Z 4942
  • Asta Z-4942
  • Cyfos
  • Holoxan
  • Holoxane
  • Ifex
  • IFO
  • IFO-Cell
  • Ifolem
  • Ifomida
  • Ifomide
  • Ifosfamidum
  • Ifoxan
  • IFX
  • Iphosphamid
  • Iphosphamide
  • Iso-Endoxan
  • Isoendoxan
  • Isophosphamide
  • Mitoxana
  • MJF 9325
  • MJF-9325
  • Naxamide
  • Seromida
  • Tronoxal
  • Z 4942
  • Z-4942
• 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

Study Arms

• Experimental: Arm I (paclitaxel, carboplatin)
  Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30-60 minutes on day 1.
  Interventions:

  • Drug: Carboplatin
  • Drug: Paclitaxel
  • Other: Quality-of-Life Assessment
• Experimental: Arm II (paclitaxel, ifosfamide)
  Patients receive ifosfamide IV over 1 hour on days 1-3 followed by paclitaxel as in Arm I.
  Interventions:

  • Drug: Ifosfamide
  • Drug: Paclitaxel
  • Other: Quality-of-Life Assessment

• Publications *: Powell MA, Filiaci VL, Hensley ML, Huang HQ, Moore KN, Tewari KS, Copeland LJ, Secord AA, Mutch DG, Santin A, Warshal DP, Spirtos NM, DiSilvestro PA, Ioffe OB, Miller DS. Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial. J Clin Oncol. 2022 Mar 20;40(9):968-977. doi: 10.1200/JCO.21.02050. Epub 2022 Jan 10.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 26, 2020): 637
• Original Estimated Enrollment (submitted: August 6, 2009): 415
• Study Completion Date: Not Provided
• Actual Primary Completion Date: March 30, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients must have newly diagnosed stage I-IV, persistent or recurrent (including unstaged) uterine carcinosarcoma (malignant mixed mullerian tumor-MMMT or with ovarian, fallopian tube or peritoneal carcinosarcoma and an enrollment date prior to 10/21/2013; pathology confirmed by site/institutional pathologist prior to enrollment) and be chemotherapy naïve as directed against their carcinosarcoma; unstaged patients (patients who have not had hysterectomy or ovarian surgery) are eligible and should be included as "unstaged" if the only histologic (pathology) documentation of the disease is a biopsy or curettage of the uterus; if these patients have documented metastatic disease, it should be assigned the appropriate stage (III/IV)
• Patients may have received prior adjuvant external beam radiation therapy and/or vaginal brachytherapy; patients should be at least 4 weeks from the completion of external beam radiotherapy prior to beginning protocol chemotherapy; patients do not need to be delayed if receiving vaginal brachytherapy only
• Gynecologic Oncology Group (GOG) performance status 0, 1, or 2
• Patients must have recovered from the effects of recent surgery, radiotherapy, or other therapy
• Patients must be free of active infection requiring antibiotics
• Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to beginning protocol chemotherapy; continuation of hormone replacement therapy is permitted
• Platelet count greater than or equal to 100,000/mcL
• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcL equivalent to Common Terminology Criteria for Adverse Events (CTCAE) version (v)3.0 grade 1
• Creatinine less than or equal to 1.5 times upper limit of normal (ULN), CTCAE v3.0 grade 1
• Bilirubin less than or equal to 1.5 times ULN (CTCAE v3.0 grade 1)
• Serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 2.5 times ULN (CTCAE v3.0 grade 1)
• Alkaline phosphatase less than or equal to 2.5 times ULN (CTCAE v3.0 grade 1)
• Serum albumin should be equal to or greater than 3 g/dL
• Neuropathy (sensory and motor) less than or equal to CTCAE v3.0 grade 1
• Patients must have signed an approved informed consent and authorization permitting release of personal health information
• Patients of childbearing potential must have a negative serum pregnancy test prior to study entry and be practicing an effective form of contraception
• Patients may have measurable disease or non-measurable disease; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each lesion must be >= 20 mm when measured by conventional techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic resonance imaging (MRI), or >= 10 mm when measured by spiral CT; measurable disease patients must have at least one "target lesion" to be used to assess progression on this protocol as defined by Response Evaluation Criteria In Solid Tumors (RECIST); tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

Exclusion Criteria:

• Patients who have received prior cytotoxic chemotherapy for management of uterine or ovarian carcinosarcoma
• Patients with a history of other invasive malignancies or with a concomitant invasive malignancy, with the exception of non-melanoma skin cancer, if there is any evidence of other malignancy being present within the last five years; patients are also ineligible if their previous cancer treatment contraindicates this protocol therapy
• Patients for whom radiotherapy is planned after or during chemotherapy prior to progression of cancer
• Patients with known hypersensitivity to Escherichia (E.) coli-derived drug preparations (pegfilgrastim and filgrastim [G-CSF])
• Patients with a known hypersensitivity to mesna or other thiol compounds
• For enrollment prior to 10/21/2013, patients who are not biopsy proven to have carcinosarcoma of the uterus, fallopian tube, peritoneum or ovary; for enrollment after 10/21/2013, patients who are not biopsy proven to have carcinosarcoma of the uterus

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: Korea, Republic of, United States
• Removed Location Countries: India

Administrative Information

• NCT Number: NCT00954174
• Other Study ID Numbers: GOG-0261; NCI-2011-01959 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); CDR0000651458; GOG-0261 ( Other Identifier: NRG Oncology ); GOG-0261 ( 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
• Original Responsible Party: Philip J. DiSaia, Gynecologic Oncology Group
• Current Study Sponsor: GOG Foundation
• Original Study Sponsor: Gynecologic Oncology Group
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Matthew A Powell; NRG Oncology

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