Regional Chemotherapy in Locally Advanced Pancreatic Cancer: RECLAP Trial

Brief summary public domain (ClinicalTrials.gov)

Background: \- Pancreatic cancer is difficult to treat because by the time most cases are diagnosed, the tumors are too large to be removed surgically. Standard intravenous chemotherapy may shrink some of the tumor, but even with chemotherapy only about 25 percent of patients will live for 1 year following diagnosis. Several preliminary studies have shown that it is safe to give chemotherapy directly into the pancreas in the area of the tumor, and that giving gemcitabine over a longer period increases the amount of drug that is available to the tumor. Researchers are interested in studying whether giving the approved pancreatic cancer chemotherapy drug gemcitabine directly into the pancreas in the area of the cancer and at a slow rate of infusion is a safe and effective treatment. Objectives: \- To test the safety and effectiveness of administering gemcitabine directly to a pancreatic tumor at a slow rate of infusion. Eligibility: \- Individuals at least 18 years of age who have been diagnosed with pancreatic cancer that is currently too large to be removed surgically but has not yet spread to other organs. Design: * Participants will be screened with a full medical history and physical examination, blood and urine tests, and imaging studies. * Participants will undergo pancreatic angiography and embolization, during which a catheter will be threaded into the blood vessels near the pancreas and a contrast dye will be used to show the blood vessels supplying the tumor. These blood vessels will then be surgically closed off. * After the embolization, gemcitabine will be given as an infusion into the area around the tumor over 24 hours. * Participants will return to the clinical center every 2 weeks after the first infusion for additional infusions of gemcitabine, using the same procedures as above. Participants will be monitored with frequent blood tests and imaging studies. * Two weeks after the fourth treatment (course 1), participants will have more imaging studies, a physical examination, and blood tests. If the tumor is shrinking, participants will have two more courses of treatment (eight more infusions of gemcitabine). * Participants will have followup visits every 3 months for 2 years following the last treatment and then every 6 months.

Detailed description public domain (ClinicalTrials.gov)

Background: * Pancreatic cancer is the fourth leading cause of cancer death in the United States. * Surgery offers the only chance at cure; however, less than 20% of patients are considered resectable at initial presentation. * A common reason for being classified as unresectable is loco-regional advanced disease. * Several phase I studies of regional administration of chemotherapy have proven safe. * The main advantage of pancreatic cancer targeted arterial perfusion of Gemcitabine is achievement of higher local bio-available active drug levels at the tumor bed. * The Regional Chemotherapy in Locally Advanced Pancreatic Cancer (RECLAP) trial is a phase I trial offering highly selective 24-hour intra-arterial administration of Gemcitabine via a subcutaneous port for patients with unresectable locally-advanced pancreatic cancer. Objectives: Primary Objective: * To evaluate feasibility and toxicity of intra-arterial gemcitabine therapy (dose limiting toxicity (DLT)). * To establish the maximum tolerated dose (MTD) Secondary Objectives: * To evaluate response rate using Response Evaluation Criteria in Solid Tumors (RECIST), positron emission tomography (PET), magnetic resonance imaging (MRI) and computed tomography (CT) perfusion criteria (European Association for the Study of the Liver (EASL)) * To determine progression free and overall survival. * To evaluate the conversion rate from unresectable or borderline resectable to potentially resectable pancreatic cancer. * To determine progression-free and overall survival. * To analyze potential selection criteria to be used in future studies for patients who present with marginally unresectable or unresectable locally-advanced pancreatic cancer that might benefit from this approach. Eligibility: * Unresectable locally-advanced pancreatic cancer. * 18 years old or greater with an Eastern Cooperative Oncology Group (ECOG) 0-2 * Laboratory and physical examination parameters within acceptable limits by standard of practice guidelines prior to surgery or chemotherapy. * No extra-pancreatic disease except regional lymph nodes. Design: * This is a dose escalation phase-I study. * Patients considered unresectable due to locally-advanced pancreatic cancer will receive selective arterial perfusion of gemcitabine over 24 hours via a subcutaneous indwelling port. * Treatment will be given on Days 1 and 14. One cycle = 4 weeks for up to six cycles. * Three to six patients will be enrolled per dose cohort. * 18 to 36 patients in 7 cohorts will be accrued plus 6 more patients at the maximum tolerated dose (MTD over 36 months. Patients will be evaluated every 2 cycles (8 weeks). Upon progression patients will be taken off study. If no progressive disease (PD), patients will continue up to 6 cycles. * Chemotherapy na(SqrRoot) ve patients and patients who received previously chemotherapy including gemcitabine will be allowed, as this mode of administration has better bioavailability, offer potential for better biological effect and less systemic toxicity profiles.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Number of Participants With Dose Limiting Toxicity (DLT ) [Cycle 1 (4 weeks), for up to 6 cycles]. Count Of Participants, Participants. 18 mg/m(2)/24h (n=4): 0; 36 mg/m(2)/24h (n=6): 1; 72 mg/m(2)/24h (n=4): 0; 96 mg/m(2)/24h (n=2): 0; 115 mg/m(2)/24h (n=1): 0.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

MTD (Maximum Tolerated Dose) [Cycle 1 (4 weeks), for up to 6 cycles]. Number, mg/ml/24h. Gemcitabine Dose Escalation (n=6): 115.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Response Using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. [Every 2 cycles (8 weeks), up to 18 weeks]. Count Of Participants, Participants. Complete response (CR): 18 mg/m(2)/24h, (n=4): 0; 36 mg/m(2)/24h (n=6): 0; 72 mg/m(2)/24h (n=4): 0; 96 mg/m(2)/24h (n=2): 0; 115 mg/m(2)/24h (n=1): 0. Partial response (PR): 18 mg/m(2)/24h, (n=4): 0; 36 mg/m(2)/24h (n=6): 0; 72 mg/m(2)/24h (n=4): 0; 96 mg/m(2)/24h (n=2): 0; 115 mg/m(2)/24h (n=1): 0. Stable disease: 18 mg/m(2)/24h, (n=4): 4; 36 mg/m(2)/24h (n=6): 4; 72 mg/m(2)/24h (n=4): 2; 96 mg/m(2)/24h (n=2): 2; 115 mg/m(2)/24h (n=1): 0. Progressive disease (PD): 18 mg/m(2)/24h, (n=4): 0; 36 mg/m(2)/24h (n=6): 2; 72 mg/m(2)/24h (n=4): 2; 96 mg/m(2)/24h (n=2): 0; 115 mg/m(2)/24h (n=1): 1.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Response Rate Using Positron Emission Tomography (PET) [Every 2 cycles (8 weeks), up to 18 weeks].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Response Rate Using Magnetic Resonance Imaging (MRI) [Every 2 cycles (8 weeks), up to 18 weeks].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Response Using Computed Tomography (CT) Perfusion Criteria European Association for the Study of the Liver (EASL1) [Every 2 cycles (8 weeks), up to 18 weeks]. Count Of Participants, Participants. Complete response (CR): 18 mg/m(2)/24h (n=4): 0; 36 mg/m(2)/24h (n=6): 0; 72 mg/m(2)/24h (n=4): 0; 96 mg/m(2)/24h (n=2): 0; 115 mg/m(2)/24h (n=1): 0. Partial response (PR): 18 mg/m(2)/24h (n=4): 0; 36 mg/m(2)/24h (n=6): 0; 72 mg/m(2)/24h (n=4): 0; 96 mg/m(2)/24h (n=2): 0; 115 mg/m(2)/24h (n=1): 0. Progressive disease (PD): 18 mg/m(2)/24h (n=4): 0; 36 mg/m(2)/24h (n=6): 4; 72 mg/m(2)/24h (n=4): 2; 96 mg/m(2)/24h (n=2): 2; 115 mg/m(2)/24h (n=1): 0. Stable disease (SD): 18 mg/m(2)/24h (n=4): 4; 36 mg/m(2)/24h (n=6): 2; 72 mg/m(2)/24h (n=4): 2; 96 mg/m(2)/24h (n=2): 0; 115 mg/m(2)/24h (n=1): 1.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Median Time to Progression [From first day of treatment to the day of progression, assessed up to 221 months]. Median, Months (Full Range). Gemcitabine Dose Escalation (n=6): 2 (1 to 221).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Median Overall Survival (OS) [Overall survival was assessed through study completion, an average of 3 years.]. Median, Months (Full Range). 18 mg/m(2)/24h, (n=4): NA (NA to NA) [No deaths.]; 36 mg/m(2)/24h (n=6): 9 (3 to 15); 72 mg/m(2)/24h (n=4): 9 (3 to 16); 96 mg/m(2)/24h (n=2): 15 (0 to 15); 115 mg/m(2)/24h (n=1): NA (NA to NA) [No deaths.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Number of Participants Who Converted From Unresectable or Borderline Resectable To Potentially Resectable Pancreatic Cancer [4 months]. Count Of Participants, Participants. 18 mg/m(2)/24h (n=4): 0; 36 mg/m(2)/24h (n=6): 0; 72 mg/m(2)/24h (n=4): 0; 96 mg/m(2)/24h. (n=2): 1; 115 mg/m(2)/24h (n=1): 1.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Number of Potential Selection Criteria to Be Used in Future Studies for Patients With Marginally Unresectable Or Unresectable Locally-Advanced Pancreatic Cancer [up to 2.5 years].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Number of Participants With Serious and Non-Serious Adverse Events [Date treatment consent signed to date off study, approximately 2 years and 2 months and 21 days]. Count Of Participants, Participants. 18 mg/m(2)/24h (n=4): 4; 36 mg/m(2)/24h (n=6): 5; 72 mg/m(2)/24h (n=4): 3; 96 mg/m(2)/24h (n=2): 2; 115 mg/m(2)/24h (n=1): 1.