Clinical Trials

PRIMARY OBJECTIVES: I. To determine the response rate and progression-free survival at 6 months in patients with endometrial, ovarian, hepatocellular carcinoma, carcinoid or islet cell cancer. II. To determine the toxicity of the combination of temsirolimus and bevacizumab in patients with endometrial, ovarian, hepatocellular carcinoma, carcinoid or islet cell cancer. SECONDARY OBJECTIVES: I. To collect blood and tumor specimens from all patients entered on the trial for possible future analysis. OUTLINE: Patients receive temsirolimus intravenously (IV) on days 1, 8, 15, and 22, and bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 3 years.

PRIMARY OBJECTIVES:

     I. To determine the maximally tolerated dose (MTD) of the combination of vismodegib and sirolimus in unresectable solid tumors. (Cohort I)

     SECONDARY OBJECTIVES:

     I. To describe the adverse event profile associated with this treatment combination.

     II. To describe the tumor responses to treatment combination.

     CORRELATIVE OBJECTIVES:

     I. To assess the effect of the sirolimus and vismodegib combination on selected biomarkers in tumor biopsies of patients with metastatic pancreatic cancer.

     II. To assess the effect of the combination of vismodegib and sirolimus on fludeoxyglucose F 18 (F18-FDG) positron emission tomography (PET) or PET/computed tomography (CT) imaging in Cohort II (MTD) patients with metastatic pancreatic cancer.

     III. To study the association of clinical (toxicity and/or tumor response or activity) with the biologic (pharmacodynamic) results obtained by examining tissue biopsies and PET or PET/CT imaging from the same patients.

     OUTLINE: This is a dose-escalation study of sirolimus.

     Patients receive sirolimus orally (PO) once daily (QD) and vismodegib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

     After completion of study treatment, patients are followed up for 3 months.

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose of the combination of ABT-888 (veliparib) and weekly topotecan (topotecan hydrochloride) in adult patients with advanced solid tumors. (Phase I) II. To identify any anti-tumor activity of this treatment combination, as assessed by objective response in patients with advanced solid tumors. (Phase I) III. To assess the confirmed response rate for patients with epithelial ovarian cancer or primary peritoneal carcinoma treated with the combination of ABT-888 and weekly topotecan. IV. To assess the toxicity of the combination of ABT-888 and weekly topotecan in patients with epithelial ovarian cancer or primary peritoneal carcinoma. (Phase II) SECONDARY OBJECTIVES: I. To identify any pharmacokinetic interactions between ABT-888 and topotecan. (Phase I and II) II. Phase I MTD: to provide preliminary view as to difference in response and toxicity based on BRCA mutation status. (Phase I) III. To determine whether topotecan stimulates adenosine diphosphate (ADP)-ribose polymer formation in circulating peripheral blood mononuclear cells. (Phase I) IV. To determine whether ABT-888 inhibits basal or topotecan-stimulated ADP-ribose polymer formation. (Phase I) V. To determine whether topotecan stimulates ADP-ribose polymer formation in circulating tumor cells and whether ABT-888 modulates this. (Phase II) VI. To assess differences in the toxicity and/or efficacy of this regimen based on BRCA 1/2 mutational status. (Phase II) VII. To determine whether pretreatment tumor cell levels of topoisomerase I, poly ADP-ribose polymerase (PARP), BRCA1, BRCA2, XRCC1, tyrosyl-deoxyribonucleic acid (DNA) phosphodiesterase 1 (TDP1), P-glycoprotein or breast cancer resistance protein (BCRP) predict response to this regimen. (Phase II) VIII. To identify, in an exploratory manner, any transcriptional profiles that may predict response to this regimen. (Phase II) OUTLINE: This is a phase I, dose escalation study of veliparib and topotecan hydrochloride followed by a phase II study. Patients receive veliparib orally (PO) on days 1-3, 8-10, and 15-17 (veliparib is omitted on days 1-3 of course 2) and topotecan hydrochloride intravenously (IV) over 30 minutes on days 2, 9, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 3 months (Phase I) or every 3 or 6 months for 5 years (Phase II).