PS-341 Plus Carboplatin in Platinum and Taxane Resistant Recurrent Ovarian Cancer, Primary Peritoneal Cancer, and Fallopian Tube Cancer

The goal of this clinical research study is to find the highest safe dose of PS-341 that can be given with carboplatin chemotherapy as a treatment for patients with ovarian, abdominal, or fallopian tube cancer. Researchers also hope to find out if giving these drugs together will help shrink or slow the growth of tumors in patients who are considered resistant to platinum drugs. The safety of these drugs will also be studied.

Official Title

A Phase I Study Evaluating the Safety and Tolerability of PS-341 and Carboplatin in Patients with Platinum- and Taxane-Resistant Recurrent Ovarian Cancer, Primary Peritoneal Cancer, and Fallopian Tube Cancer

Conditions

– Ovarian Cancer- Primary Peritoneal Cancer- Fallopian Tube Cancer

Study Type

Study Design

Further Details

1. Establish the dose-limiting toxicity and maximally tolerated dose of PS-341 and carboplatinum when given in combination to patients with platinum- and taxane-resistant recurrent ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. 2. Determine the proportion of patients treated with PS-341 in combination with carboplatinum who achieve a confirmed complete response (CR) or partial response (PR) or have stable disease (SD).

Study Start

Eligibility & Criteria

Genders Eligible for Study: Female Criteria Inclusion:Patients must have histologically-confirmed ovarian cancer, primary peritoneal cancer, or fallopian tube cancer with advanced and/or metastatic disease. All patients must be considered platinum- and taxane- resistant. Platinum resistance is defined as: a) Progression of disease during platinum or taxane chemotherapy, or b) Progression of disease within 6 months of completing platinum or taxane chemotherapy c) Failure to achieve a complete response, with persistent macroscopic disease, after 6 cycles of chemotherapy, if the last two cycles had no measurable change in disease status Patients may have had any number of prior chemotherapy regimens, except high dose chemotherapy an/or peripheral blood stem cell transplantation (high dose: higher than the standard doses of chemotherapy) Patients must have measurable disease. Zubrod performance status of < 2. Expected survival of three months or longer. Patients must give voluntary written informed consent before performance of any study-related procedure not part of normal medical care. Adequate liver, renal and bone marrow function, defined as: Absolute neutrophil count (ANC) >1.5×109 /L. Platelets >100×109/L Total bilirubin <1.7 umol/L Alanine transaminase (ALT) and aspartate transaminase (AST) <1.5xULN Alkaline phosphatase <2.5xULN. Serum creatinine <1.5xULN. Exclusion:Chemotherapy within four weeks of first course of PS-341. (Patients may have been on hormonal therapy). Patients who previously received high-dose chemotherapy (higher than the standard doses of chemotherapy) and/or peripheral blood stem cell transplantation. Radiation therapy within four weeks of enrollment (excepting palliative XRT). Patients not recovered from toxic effects of previous chemotherapy, radiation therapy, or antibody therapy. Patients with > Grade 2 peripheral neuropathy. Surgery within four weeks of study enrollment. History of severe hypersensitivity reaction to carboplatin Electrocardiographic evidence of acute ischemia or new conduction system abnormalities. Myocardial infarction within six months of enrollment. Patients with brain metastases or central nervous system disease as evidenced by clinical symptoms. History of other malignancy, except nonmelanoma skin cancer or carcinoma in-situ of the cervix, unless in complete remission and off all therapy for that disease for a minimum of 5 years. Chemotherapy given for prior cancers will not exclude patients from participating in this study. Patients with previously documented human immunodeficiency virus (HIV) infection. HIV-positive patients are excluded from the study based on theoretical concerns regarding the effect of PS-341 on certain aspects of immune function. NF-KB is a critical T cell activation protein (including through CD40L/CD 154 stimulation) and also is involved in cytokine production. Because PS 341 effectively blocks NF-KB and therefore could reduce or block the ability of T lymphocytes and other immune cells to fight HIV, PS-341 should not be administered to HIV-positive patients. Additional experiments in animal models are being conducted to better elucidate the effects of PS-341 on HIV. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Other serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol. Patients who are pregnant, suspected to be pregnant, or breast-feeding. Patients with a known hypersensitivity to PS-341, boron, or manitol.

Total Enrolment

24

Contact Details

[1] Pedro T. Ramirez, MD, Study Chair, University of Texas M. D. Anderson Cancer Center