GOG 261: A Randomized Phase III Trial of Paclitaxel Plus Carboplatin Versus Ifosfamide Plus Paclitaxel in Chemotherapy-Naïve Patients with Newly Diagnosed Stage I-IV, Persistent or Recurrent Carcinosarcoma (Mixed Mesodermal Tumors) of the Uterus, Fallopian Tube, Peritoneum, or Ovary
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.
* Regimen I: (experimental arm): paclitaxel over 3 hours, and carboplatin over 1 hour, all given by vein as an outpatient on day 1 of a 3-week cycle.
* Regimen II (standard arm): ifosfamide (by vein on days 1, 2, and 3) over 1 hour on days 1-3, paclitaxel (by vein on day 1) over 3 hours.
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.
1.Patients must have newly diagnosed Stage I-IV, persistent or recurrent (including unstaged) uterine, fallopian tube, peritoneal or ovarian carcinosarcoma (malignant mixed mullerian tumor-MMMT) and be chemotherapy naïve as directed against uterine carcinosarcoma. Review of the pathologic specimen from the uterus is required. 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).
2.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 radiotherapy prior to beginning protocol chemotherapy.
3.Patients must have a GOG Performance Status of 0, 1, or 2.
4.Patients must have recovered from effects of recent surgery, radiotherapy or other therapy.
5.Patients must be free of active infection requiring antibiotics.
6.Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration. Continuation of hormone replacement therapy is permitted.
7.Patients must have adequate:
oBone marrow function: Platelet count greater than or equal to 100,000/mcl, and ANC count greater than or equal to 1,500/mcl, equivalent to CTCAE v3.0 Grade 1.
oRenal function: creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), CTCAE v3.0 Grade 1.
oHepatic function: Bilirubin less than or equal to 1.5 x ULN (CTCAE v3.0 Grade 1). SGOT and alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v3.0 Grade 1). Serum Albumin should be equal to or greater than 3g/dL.
oNeurologic function: Neuropathy (sensory and motor) less than or equal to CTCAE v3.0 Grade 1.
8.Patients must have signed an approved informed consent and authorization permitting release of personal health information.
9.Patients of childbearing potential must have a negative serum pregnancy test prior to study entry and be practicing an effective form of contraception.
10. 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, CT, and 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 RECIST (Section 8). 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.
11.Patients must be 18 years of age or older
12.Female patients of all ethnic and racial groups
13.Spanish speaking patients.