Evaluation of Paclitaxel (Taxol, NSC #673089), Carboplatin (Paraplatin, NSC #241240), and BSI-201 (NSC #746045, IND #71,677) in the Treatment of Advanced, Persistent, or Recurrent Uterine Carcinosarcoma

Sanofi

Status and phase: Completed; Phase 2

Conditions: Uterine Carcinosarcoma

Treatments: Drug: carboplatin; Drug: BSI-201 (Iniparib); Drug: paclitaxel

Study type: Interventional

Funder types: NETWORK; Industry

Identifiers

NCT00687687

GOG 0232C

20070103 (Other Identifier)

TCD11615

Details and patient eligibility

About

To estimate the antitumor activity of paclitaxel, carboplatin, plus BSI-201 in patients with recurrent or advanced uterine carcinosarcomas.

Based on data generated by BiPar/Sanofi, it is concluded that iniparib does not possess characteristics typical of the PARP inhibitor class. The exact mechanism has not yet been fully elucidated, however based on experiments on tumor cells performed in the laboratory, iniparib is a novel investigational anti-cancer agent that induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging modalities in tumor cell lines. Investigations into potential targets of iniparib and its metabolites are ongoing.

Enrollment: 22 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients must have advanced (stage III or IV), persistent or recurrent uterine carcinosarcoma with documented disease progression. Histologic confirmation of the original primary tumor is required.
• All patients must have 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 greater than 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT, and MRI, or greater than 10 mm when measured by spiral CT.
• Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST (Section 8.1). 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.
• Patients must have a GOG Performance Status of 0, 1, or 2.
• Adequate bone marrow,renal, hepatic, and neurological function

Exclusion criteria

• Patients who have received prior cytotoxic chemotherapy for management of uterine carcinosarcoma.
• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies as noted in Sections 3.23 and 3.24 are excluded if there is any evidence of other malignancy being present within the last five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of uterine carcinosarcoma within the last five years are excluded. Prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease.
• Patients MAY have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease.
• Patients who have symptomatic or untreated brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and corticosteroids.
• Patients who have a significant history of cardiac disease, i.e., myocardial infarction (MI) within 6 months of study registration, unstable angina, congestive heart failure (CHF) with New York Heart Association (NYHA) > class II, or uncontrolled hypertension.
• Patients who have a history of seizure disorder or are currently on anti-seizure medication.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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22 participants in 1 patient group

Pacitaxel/Carboplatin/Iniparib

Experimental group

Description:

Participants will be administered pacitaxel, carboplatin and BSI-201 (Iniparib) in 21 day treatment cycles. Treatment will continue until disease progression or adverse effects prohibit further therapy.

Treatment:

Drug: BSI-201 (Iniparib)

Drug: carboplatin

Drug: paclitaxel