Archives: Clinical Trials

This is a single arm phase II trial assessing the potential activity of combination PEGPH20 plus Gemcitabine with radiotherapy in ten patients with localized, unresectable pancreatic adenocarcinoma.

The objective of this study is to estimate the R0 resection rate in patients with Resectable Pancreatic Ductal Adenocarcinoma (R-PDAC) as well as those with Resectable Pancreatic Ductal Adenocarcinoma (BR-PDAC) independently in response to neoadjuvant sequential therapy of combination nab-paclitaxel and gemcitabine followed by stereotactic body radiotherapy (SBRT).

To evaluate the safety, tolerability, and efficacy of TTI-101 given in combination with Stereotactic Body Radiation Therapy (SBRT) in borderline resectable pancreatic ductal adenocarcinoma.

This phase II trial studies how well niraparib and dostarlimab work in treating patients with germline or somatic BRCA1/2 and PALB2 mutated pancreatic cancer that has spread to other places in the body (metastatic). Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as dostarlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving niraparib and dostarlimab may kill more tumor cells.

Pancreatic cancer is an aggressive disease with an extremely poor prognosis. It is the forth leading cause of cancer-related fatalities, with an estimated one-year and five-year survival rate of 21% and 5%, respectively. Despite recent progress, the median survival time is 6-10 months for patients with locally advanced disease and 3-6 months for metastatic disease (1). The anti-metabolite gemcitabine has become the standard chemotherapy for locally advanced and metastatic pancreatic cancer, after demonstrating an improved rate of clinical benefit response and an overall survival advantage over 5-FU (2). In addition to its clinical effectiveness gemcitabine has a manageable toxicity profile, making it an attractive agent to investigate in combination with newer agents. Series of phase III trials were conducted examining the efficacy of the combination of gemcitabine and a second cytotoxic agent, including 5-FU, cisplatin, oxaliplatin and irinotecan. These gemcitabine doublets demonstrated no survival advantage over single-agent gemcitabine (3-6). However, the rationale for continuing to study gemcitabine-based combinations remains compelling.

Curcumin (diferuloylmethane) is a natural compound derived from the rhizome of Curcuma Longa, an East Indian plant, commonly called turmeric. It has been shown to possess potent anti-inflammatory and anti-oxidative properties, for which it has a long history of dietary use as a food additive. Curcumin has also a potent anti-proliferative effects against a variety of cancer cell lines in vitro, which stem from its ability to modulate many intracellular signal transduction pathways (7). Human phase I-II studies found curcumin to be safe, and indicated no dose-limiting toxicity when taken by mouth at doses up to 10 g/day (8, 9). This data, together with the dismal therapeutic options available for pancreatic cancer patients, suggest that curcumin warrants investigation in this setting. Investigators from MD Anderson Cancer Center and Rambam Medical Center in Haifa, have recently initiated, separately, a phase II study of single agent Curcumin in patients with pancreatic cancer (10).

One of the lessons learned from cancer research in recent decades is that combination strategies can provide dramatic improvement in a therapy's safety and efficacy over mono-therapeutic regiments, especially if the combined drugs differ in their mode of action. In a recent paper that was accepted for publication we demonstrated, in vitro, the mechanism, clinical importance and implications of a novel combinatorial therapy, of celecoxib and curcumin, that was discovered in our lab, in inhibiting the growth of several pancreatic cell lines. P-34 (expressing high levels of COX -2), MiaPaca (Expressing low levels of COX-2) and Panc-1 (no expression of COX -2) cell lines were exposed to different concentrations of celecoxib (0-40µM), curcumin (0-20µM) and their combination. In P-34 cells, curcumin synergistically potentiated the inhibitory effect of celecoxib on cell growth. The growth inhibition was associated with inhibition of proliferation and induction of apoptosis.

These experiments further demonstrate, for the first time, that the combination effect is correlated with synergistic augmentation of apoptosis and involves down-regulation of COX-2 protein.

The present study evaluates gemcitabine in combination with curcumin and celecoxib for patients with pancreatic cancer.

This phase I trial studies the side effects and the best dose of alisertib when given together with gemcitabine hydrochloride in treating patients with solid tumors or pancreatic cancer that is metastatic or cannot be removed by surgery. Alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving alisertib with gemcitabine hydrochloride may be an effective treatment for solid tumors or pancreatic cancer.

The outcomes of concurrent EUS-guided intra-tumour injection of P-32 microparticles (OncoSil; OncoSil Medical, Australia) with chemotherapy in locally advanced pancreatic carcinoma in the local population is uncertain.

The aim of the current study is to assess efficacy and safety of the intervention in the local population. We hypothesis that the intervention is safe and useful for tumour downstaging.

Cardiovascular diseases and cancers, the two leading causes of death in Canada, require cholesterol to sustain their progression. All cells require cholesterol, but cancer cells have much higher needs to sustain growth, division and metastasis. The availability of new cholesterol-lowering drugs developed to protect patients from heart diseases has resulted in unprecedented low levels of cholesterol. The combination of atorvastatin, ezetimibe and Repatha, which are 3 cholesterol-lowering drugs used in combination, is safe, well tolerated and efficient over years of treatment. Recent reports indicate that abundant cholesterol supplies are required to sustain the progression of pancreatic ductal adenocarcinomas. This proof-of-concept study aims to verify the feasibility, the acceptability and gain preliminary data on adding a cholesterol shortage on top of FOLFIRINOX (standard chemotherapy) in newly diagnosed patients with locally advanced pancreatic adenocarcinomas or metastatic pancreatic adenocarcinomas. It is expected that a drug-induced cholesterol shortage will slow-down or stop the progression of pancreatic adenocarcinomas while increasing the response to chemotherapy.

This is a randomized prospective clinical study comparing the Acquire Biopsy Device to SharkCore Biopsy Device.

Pancreatic cancer is an aggresive type of cancer with poor mean survival rates despite improvements in chemotherapy regimens and advances in surgical techniques. Surgery is the only therapeutic option with an intend to treat. Pancreaticoduodenectomy is indicated for malignancy in the pancreatic head as well as other periampullary tumors. One of the most fatal complications after Whipple operation is postoperative pancreatic fistula as a result of pancreatojejunostomy leakage. Various risk factors for pancreatojejunostomy leakage have been proposed, while there are others less studied.