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

Phase 3

Conditions: Stage IA Uterine Sarcoma AJCC v7
Mixed Mesodermal (Mullerian) Tumor
Stage IA Ovarian Cancer AJCC v6 and v7
Stage IB Fallopian Tube Cancer AJCC v6 and v7
Stage IC Ovarian Cancer AJCC v6 and v7
Stage IIA Uterine Sarcoma AJCC v7
Stage IIC Fallopian Tube Cancer AJCC v6 and v7
Stage IIIA Ovarian Cancer AJCC v6 and v7
Stage IIIB Uterine Sarcoma AJCC v7
Stage IV Fallopian Tube Cancer AJCC v6 and v7

Interventions: Drug: Carboplatin
Drug: Ifosfamide
Drug: Paclitaxel
Other: Quality-of-Life Assessment

Registration Number: NCT00954174

Lead Sponsor: GOG Foundation

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.

Recruitment & Eligibility

Status: UNKNOWN

Sex: Female

Target Recruitment: 637

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II (paclitaxel, ifosfamide)	Quality-of-Life Assessment	Patients receive ifosfamide IV over 1 hour on days 1-3 followed by paclitaxel as in Arm I.
Arm I (paclitaxel, carboplatin)	Quality-of-Life Assessment	Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30-60 minutes on day 1.
Arm I (paclitaxel, carboplatin)	Paclitaxel	Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30-60 minutes on day 1.
Arm I (paclitaxel, carboplatin)	Carboplatin	Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30-60 minutes on day 1.
Arm II (paclitaxel, ifosfamide)	Paclitaxel	Patients receive ifosfamide IV over 1 hour on days 1-3 followed by paclitaxel as in Arm I.
Arm II (paclitaxel, ifosfamide)	Ifosfamide	Patients receive ifosfamide IV over 1 hour on days 1-3 followed by paclitaxel as in Arm I.

Primary Outcome Measures

Name	Time	Method
Overall Survival	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.

Secondary Outcome Measures

Name	Time	Method
Duration of Progression-free Survival	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	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	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	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	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	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.

Trial Locations

Locations (535): University of Alabama at Birmingham Cancer Center
🇺🇸
Birmingham, Alabama, United States
University of South Alabama Mitchell Cancer Institute
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Mobile, Alabama, United States
Saint Joseph's Hospital and Medical Center
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Phoenix, Arizona, United States
Mayo Clinic Hospital in Arizona
🇺🇸
Phoenix, Arizona, United States
Mayo Clinic in Arizona
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Scottsdale, Arizona, United States
University of Arizona Cancer Center-Orange Grove Campus
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Tucson, Arizona, United States
Banner University Medical Center - Tucson
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Tucson, Arizona, United States
University of Arizona Cancer Center-North Campus
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Tucson, Arizona, United States
Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
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Jonesboro, Arkansas, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
🇺🇸
Burbank, California, United States
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University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States