Clinical Trials

The purpose of this study is to examine the safety and evaluate the response of VB-111 on DTC.

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 evaluate the efficacy of single agent ABT-888 (veliparib) (NSC 737664) in BRCA carriers with metastatic breast cancer based on response rate (RECIST criteria). SECONDARY OBJECTIVES: I. To conduct subset analysis on BRCA1 vs. BRCA2 and hormone receptor status. II. To evaluate progression-free survival of patients on single-agent ABT-888. III. To further describe the safety and tolerability of ABT-888 (NSC 737664) as a single agent and in combination with carboplatin for BRCA-associated breast cancer. IV. To evaluate the pharmacokinetics of ABT-888 (NSC 737664) alone and in combination with carboplatin. V. To assess the relationship between the level of PARP inhibition by ABT-888 and biomarkers of DNA damage in PBMC's and in tumor VI. To explore the relationship between biomarkers of drug effect and progression-free survival. VII. To evaluate the efficacy and safety of the combination of carboplatin and ABT-888 in patients who have failed single agent ABT-888. VIII. To conduct subset analysis on BRCA1 vs. BRCA2 and hormone receptor status. OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status (0-1 vs 2), and hormone status (estrogen receptor [ER]- and/or progesterone receptor [PR]-positive vs ER- and/or PR-negative). Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive oral veliparib twice daily on days 1-21. ARM II: Patients receive carboplatin IV over 30 minutes on day 1 and veliparib as in arm I. In both arms, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood and hair follicle sample collection for pharmacokinetics and other laboratory studies. After completion of study therapy, patients are followed up every 3-6 months.

This is an open-label study that investigates the impact of a dose ramp-up strategy for sorafenib in patients with HCC. Clinical trial and post-marketing data suggest that sorafenib dose reductions and discontinuations due to adverse events are common and limit the drug's effectiveness. It is our hypothesis that a dose escalation strategy for sorafenib will improve the tolerability and allow a greater percentage of patients to remain on drug. The primary end-point of the study is the total accumulated and median daily dose of sorafenib delivered at month 2 and 4.

OBJECTIVES: Primary - To collect clinical data and family histories and blood and/or tissue samples from patients diagnosed with pancreatic diseases, including pancreatic cancer, for use in future studies. - To collect information regarding food preparation and intake in these patients. Secondary - To make available to researchers medical data and biospecimens to enable them to develop better ways to screen people at risk for pancreatic conditions, including pancreatic cancer. - To investigate genes or substances that increase susceptibility of developing pancreatic conditions. - To find agents that may help prevent, treat, or cure these conditions. - To learn whether inherited factors increase the risk of pancreatic diseases, pancreatic cancer, or other cancers. OUTLINE: This is a multicenter study. Patients complete two 1-hour surveys assessing health, clinical and family history of pancreatic conditions including cancer, and food preparation and intake. Patients also complete a 15- to 30-minute follow up survey at 6 months and 1 year to assess health, health practices, and family history. A review of the patient's medical information is obtained from the medical record. Blood samples are collected for future research studies. Oral cells and stool samples may also be collected for future studies.

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).

Unfortunately, despite the best clinical efforts and breakthroughs in biotechnology, most patients diagnosed with pancreatic cancer continue to die from the rapid progression of their disease. The primary reason for this is that the disease is typically without symptoms until significant local and/or distant spread has occurred and is often beyond the chance for cure at the time of the diagnosis. The lack of any treatment to significantly increase long term survival rates is reflected by the poor outcomes associated with this disease, specifically time to disease progression and overall survival. These disappointing facts typically shape discussions of treatment options for patients with this disease. However, another important part of the body is now being looked at as a target for therapy against this disease -- the immune system. Scientists have clearly shown that pancreatic tumor cells produce a number of defective proteins, or express normal proteins in highly uncharacteristic ways, as part of this cancer. In some cancers, these abnormalities can cause an immune response to the cancer cells much in the way one responds to infected tissue. In progressive cancers however, the immune system fails to identify or respond to these abnormalities and the cancer cells are not attacked or destroyed for reasons not yet fully understood. This clinical trial proposes a new way to stimulate the immune system to recognize the abnormal components found in pancreatic cancer cells and to stimulate an immune response that destroys or blocks the growth of the cancer. This new method of treatment helps the immune system of pancreatic cancer patients to "identify" the cancerous tissue so that it can be eliminated from the body. As an example, most people are aware that patients with certain diseases may require an organ transplant to replace a damaged kidney or heart. After receiving their transplant these patients receive special drugs because they are at great danger of having an immune response that destroys or "rejects" the transplanted organ. This "rejection" occurs when their immune system responds to differences between the cells of the transplanted organ and their own immune system by attacking the foreign tissue in the same way as it would attack infected tissue. When the differences between foreign tissues and the patient's body are even larger, perhaps like differences between organs from pigs and the immune system cells of humans, the rejection is very rapid, highly destructive and the immunity it generates is long lasting. This is called hyperacute rejection and the medicine used to immunize patients in this protocol tries to harness this response to teach a patient's immune system to fight their pancreatic cancer just as the body would learn to reject a transplanted organ from an animal. To do this, the investigators have placed a mouse gene into human pancreatic cancer cells so that the immune system will easily recognize them as foreign, stimulating the patient immune system to attack the vaccine cells just as they would any other animal cells. As part of the process of destroying the immunotherapy cells, the patient immune system is stimulated to identify as many differences from normal human as possible. This extra stimulation is thought to encourage immune responses against the pancreatic cancer in the patient based on shared abnormalities of pancreatic cancer vaccine cells and the patient's pancreatic cancer cells. In this experimental therapy, patients are given injections of an immunotherapy consisting of two types of cancer cells that the investigators have modified to make them more easily recognized and attacked by the immune system. The investigators propose to test this new treatment in patients with pancreatic cancer who have undergone tumor removal surgery but remain at extremely high risk of disease progression to demonstrate that treatment with the immunotherapy increases the time until the tumor recurs or increases overall survival when given in combination with the current standard of care therapy for this disease. For more information, please see our study specific website: www.pancreaticcancer-clinicaltrials.com

Pancreatic cancer (PC) is the most lethal of all major cancers with a five year survival rate of 5 %. While stage I and II tumors leads to an improvement in survival, almost all PCs are currently diagnosed at more advanced non-resectable stages since minimally invasive technique which is capable of screening early-stage PC does not exist. Serum CA19-9 is not recommended as a screening technique because of its low sensitivity and specificity. Imaging modalities such as MRI, CT, EUS and ERCP are more accurate but are not appropriate screening tools due to their high cost, discomfort and complications. Therefore, there is a strong demand for a screening tool with high sensitivity and specificity which is highly acceptable for the patient. The investigators would like to standardize the detection method of pancreatic cancer that uses the duodenal juice as an optional endoscopic diagnosis. It's a very useful chance to collect pancreatic juice from duodenum, it is called "duodenal juice" ,if we collect them without additional invasion. The investigators would like to collect duodenal juice during undergoing upper gastrointestinal endoscopy and analyze the pancreatic tumor markers in duodenal juice. A definite diagnosis of the patient is made with histology, cytology or imaging diagnosis and the result of each definite diagnosis is correlated to the each marker analyzing result of duodenal juice. Therefore this study can be positioned as a feasibility study to confirm clinical performance.

PRIMARY OBJECTIVES: I. Response rate. We will compare the cetuximab/ARQ 197 (tivantinib) combination with cetuximab single agent activity. SECONDARY OBJECTIVES: I. Continuous tumor shrinkage. II. Progression-free survival (PFS). III. Overall survival (OS). IV. Endpoints I), II), and III) above, as well as response rates, will be assessed and compared between treatment arms in the subgroup of patients with high c-MET expression (anticipated to be ~84% of patients, and/or high c-MET copy number (anticipated >10% and largely overlapping with MET IHC). V. Single agent activity for ARQ 197 (tivantinib) in patients who have failed cetuximab. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive cetuximab intravenously (IV) over 60-120 minutes on days 1 and 15 and tivantinib orally (PO) twice daily (BID) on days 1-28. ARM II: Patients receive cetuximab IV over 60-120 minutes on days 1 and 15. Patients who fail cetuximab as a single agent may receive single agent tivantinib PO BID on days 1-28. In both arms, courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 5 years.