test

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

Conditions

Ovarian Carcinosarcoma | Recurrent Ovarian Epithelial Cancer | Recurrent Primary Peritoneal Cavity Cancer | Recurrent Uterine Sarcoma | Stage I Uterine Sarcoma | Stage IA Ovarian Epithelial Cancer | Stage IA Primary Peritoneal Cavity Cancer | Stage IB Ovarian Epithelial Cancer | Stage IB Primary Peritoneal Cavity Cancer | Stage IC Ovarian Epithelial Cancer | Stage IC Primary Peritoneal Cavity Cancer | Stage II Uterine Sarcoma | Stage IIA Ovarian Epithelial Cancer | Stage IIA Primary Peritoneal Cavity Cancer | Stage IIB Ovarian Epithelial Cancer | Stage IIB Primary Peritoneal Cavity Cancer | Stage IIC Ovarian Epithelial Cancer | Stage IIC Primary Peritoneal Cavity Cancer | Stage III Uterine Sarcoma | Stage IIIA Ovarian Epithelial Cancer | Stage IIIA Primary Peritoneal Cavity Cancer | Stage IIIB Ovarian Epithelial Cancer | Stage IIIB Primary Peritoneal Cavity Cancer | Stage IIIC Ovarian Epithelial Cancer | Stage IIIC Primary Peritoneal Cavity Cancer | Stage IV Ovarian Epithelial Cancer | Stage IV Primary Peritoneal Cavity Cancer | Stage IV Uterine Sarcoma | Uterine Carcinosarcoma

Trial Phase

Phase 3

Trial Purpose and Description

Trial Purpose

This randomized phase III trial is studying giving paclitaxel together with carboplatin to see how well it works compared with giving paclitaxel together with ifosfamide in treating patients with newly diagnosed persistent or recurrent uterine, ovarian, fallopian tube, or peritorium cavity cancer. 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 or by stopping them from dividing. It is not yet known whether paclitaxel is more effective when given together with carboplatin or ifosfamide in treating patients with uterine, ovarian, fallopian tube, or peritorium cavity cancer.


Trial 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 stratified according to history of pelvic radiation (any vs none), disease status/stage at time of study registration (stage I-II [pelvic lymph nodes not surgically and pathologically assessed] vs Federation of Gynecology and Obstetrics [FIGO] stage I-II [pelvic lymph nodes surgically and pathologically assessed] vs FIGO stage III-IV vs recurrent), and measurable disease (any vs none). Patients are randomized to 1 of 2 treatment arms.

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

ARM II: Patients receive paclitaxel as in arm I and ifosfamide IV over 1 hour on days 1-3.

In both arms, treatment repeats every 21 days for 6-10 courses in the absence of disease progression or unacceptable toxicity. Archival formalin-fixed and paraffin-embedded tumor tissue samples and a pre-treatment blood sample are collected for further analysis. Patients also complete quality of life (FACT-G, FACT-En TOI) and neurotoxicity (FACT/GOG-Ntx subscale) assessments at baseline and at weeks 6, 15, and 26.

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.


Participation Guidelines

Age:
18 Years - N/A
Gender:
Female

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 ; 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 >= 100,000/mcL

- Absolute neutrophil count (ANC) >= 1,500/mcL equivalent to Common Terminology
Criteria for Adverse Events (CTCAE) v3.0 Grade 1

- Creatinine =< 1.5 times upper limit of normal (ULN)

- Bilirubin =< 1.5 times ULN

- Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 times ULN

- Alkaline phosphatase =< 2.5 times ULN

- Serum albumin >= 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 E. coli-derived drug preparations
(pegfilgrastim and filgrastim [G-CSF])

- Patients with a known hypersensitivity to mesna or other thiol compounds

- Patients who are not biopsy proven to have carcinosarcoma of the uterus, fallopian
tube, peritoneum or ovary are ineligible
Sponsor:
Gynecologic Oncology Group
National Cancer Institute (NCI)
Dates:
August 2009
Last Updated:
February 27, 2014
Study HIC#:

Clinicaltrials.gov ID: NCT00954174