Paclitaxel and Carboplatin or Ifosfamide in Treating Patients With Newly Diagnosed Persistent or Recurrent Uterine Carcinosarcoma - Full Text View

Sponsors and Collaborators:	Gynecologic Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00954174

Purpose

RATIONALE: 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 carcinosarcoma.

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 carcinosarcoma.

Condition	Intervention	Phase
Sarcoma	Drug: carboplatin Drug: ifosfamide Drug: paclitaxel	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Soft Tissue Sarcoma

Drug Information available for: Paclitaxel Carboplatin Ifosfamide

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Duration of overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Duration of progression-free survival [ Designated as safety issue: No ]
Toxicity as assessed by CTCAE version 3.0 [ Designated as safety issue: Yes ]
Quality of life [ Designated as safety issue: No ]

Estimated Enrollment:	415
Study Start Date:	August 2009
Estimated Primary Completion Date:	February 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1.	Drug: carboplatin Given IV Drug: paclitaxel Given IV
Arm II: Experimental Patients receive paclitaxel as in arm I and ifosfamide IV over 1 hour on days 1-3.	Drug: ifosfamide Given IV Drug: paclitaxel Given IV

Detailed Description:

OBJECTIVES:

Primary

To determine if treatment with paclitaxel and carboplatin does not result in an inferior death rate when compared to paclitaxel and ifosfamide in chemotherapy-naïve patients with newly diagnosed stage I-IV persistent or recurrent uterine carcinosarcoma.

Secondary

To determine if treatment with combination paclitaxel and carboplatin does not result in an inferior progression-free survival when compared to paclitaxel and ifosfamide.
To determine if acute toxicity, specifically physician-assessed neurotoxicity and infection, associated with combination paclitaxel and carboplatin is reduced compared to that of paclitaxel and ifosfamide.
To determine if treatment with combination paclitaxel and carboplatin is associated with superior patient reported quality of life and neurotoxicity scores compared to that of paclitaxel and ifosfamide.

Tertiary

To bank formalin-fixed and paraffin-embedded tumor tissue and DNA extracted from whole blood specimens 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 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 IV over 3 hours and carboplatin IV over 1 hour 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Biopsy confirmed uterine carcinosarcoma (malignant mixed müllerian tumor)
- Newly diagnosed disease
- Stage I-IV* disease
- Persistent or recurrent disease
- Chemotherapy-naive disease NOTE: *Unstaged patients (patients who have not had hysterectomy 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)
Measurable or nonmeasurable disease
- Measurable disease is defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension as ≥ 20 mm by conventional techniques (e.g., palpation, plain s-ray, CT scan, MRI) or ≥ 10 mm by spiral CT scan
- Patients with measurable disease must have ≥ 1 "target lesion" to be used to assess disease progression as defined by RECIST criteria
- 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 ≥ 90 days after completion of radiotherapy

PATIENT CHARACTERISTICS:

GOG performance status 0-2
Platelet count ≥ 100,000/mm^3
ANC ≥ 1,500/mm^3
Creatinine ≤ 1.5 times upper limit of normal (ULN)
Bilirubin ≤ 1.5 times ULN
SGOT ≤ 2.5 times ULN
Alkaline phosphatase ≤ 2.5 times ULN
Serum albumin ≥ 3 g/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Neuropathy (sensory and motor) ≤ CTCAE v3.0 grade 1
No active infection requiring antibiotics
No concurrent or history of other invasive malignancies, except for nonmelanoma skin cancer, within the past 5 years
No known hypersensitivity to E. coli-derived drug preparations (pegfilgrastim and filgrastim [G-CSF]), mesna, or other thiol compounds

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from the effects of recent surgery, radiotherapy, or other therapy
No prior cytotoxic chemotherapy for management of uterine sarcoma
No prior cancer treatment that contraindicates this protocol therapy
At least 4 weeks since prior adjuvant external beam radiotherapy and/or vaginal brachytherapy
At least 1 week since prior hormonal therapy directed at the malignant tumor
- Continuation of hormone replacement therapy allowed
No planned radiotherapy after or during study treatment prior to progression of cancer

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00954174

Sponsors and Collaborators

Gynecologic Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Matthew A. Powell, MD

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Gynecologic Oncology Group ( Philip J. DiSaia )
Study ID Numbers:	CDR0000651458, GOG-0261
Study First Received:	August 6, 2009
Last Updated:	August 26, 2009
ClinicalTrials.gov Identifier:	NCT00954174 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

uterine carcinosarcoma
stage I uterine sarcoma
stage II uterine sarcoma

stage III uterine sarcoma
stage IV uterine sarcoma
recurrent uterine sarcoma

Study placed in the following topic categories:

Antimitotic Agents
Carboplatin
Recurrence
Neoplasms, Connective and Soft Tissue
Malignant Mesenchymal Tumor
Soft Tissue Sarcomas
Ifosfamide
Paclitaxel
Uterine Sarcoma

Mechlorethamine
Tubulin Modulators
Sarcoma
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Alkylating Agents
Carcinosarcoma
Isophosphamide mustard

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators
Antimitotic Agents
Carboplatin
Pharmacologic Actions
Neoplasms, Connective and Soft Tissue
Neoplasms
Ifosfamide

Paclitaxel
Therapeutic Uses
Tubulin Modulators
Sarcoma
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Alkylating Agents
Neoplasms, Complex and Mixed
Carcinosarcoma
Isophosphamide mustard

ClinicalTrials.gov processed this record on September 11, 2009