AZD2281 and Cisplatin Plus Gemcitabine to Treat Solid Tumor Cancers

Inclusion Criteria

• •Patients must have histologically confirmed (by the NIH pathology department) solid tumor malignancy that is metastatic or unresectable for which standard curative measures do not exist, or are associated with minimal patient survival benefit.
• •To minimize the risk of bone marrow toxicity in this population, patients must have had no more than two prior severely myelosuppressive cytotoxic chemotherapy regimens.
• •Any prior therapy must have been completed greater than 2 weeks prior to enrollment on the protocol in patients participating in a phase 0 (eIND\]) study, or greater than or equal to 4 weeks in patients participating in a regulatory IND study, and the participants must have recovered to eligibility levels (CTCAE Grade less than or equal to 1) from prior toxicity. Prior radiation or surgery should have been completed greater than or equal to 4 weeks prior to study enrollment and all associated toxicities resolved to eligibility levels (prior irradiated tumors will be considered for biopsy if signs of disease progression are present).
• •Age greater than or equal to18 years. Because no dosing or AE data are currently available on the use of AZD2281 in patients less than 18 years of age, children are excluded from this study, but may be eligible for future pediatric Phase I combination trials.
• •Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60 percent).
• •Life expectancy greater than or equal to 3 months.
• •Patients must have normal organ and marrow function as defined below:
• •* Absolute neutrophil count greater than or equal to 1,500/microL
• •* Platelets greater than or equal to 100,000/microL
• •* Total bilirubin less than or equal to 1.5 times institutional upper limit of normal
• •* AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times institutional upper limit of normal
• •* Creatinine less than or equal to 1.5 times institutional upper limit of normal
• •OR
• •Creatinine clearance greater than or equal to 60 mL/minute for patients with creatinine levels greater than 1.5 times institutional upper limit of normal.
• •* The effects of AZD2281 on the developing human fetus are unknown. For this reason, and because cisplatin and gemcitabine used in this trial are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after completion of study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• •* Ability to understand and the willingness to sign a written informed consent document.
• •* Patients who have previously received cisplatin or gemcitabine, or both, are eligible to enter the trial.