Ibrutinib Combined With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Cancer

Brief summary public domain (ClinicalTrials.gov)

Gemcitabine and nab-paclitaxel is a standard regimen (NCCN, Category 1) for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). However, further improvement in treatment is needed. Increasingly, the nature of the immune infiltrate in PDAC appears to be tumor promoting. In preclinical studies, ibrutinib treatment, presumably by reprogramming B cells, results in increased CD8+ T cells to assist in tumor control. Preclinical studies of ibrutinib plus gemcitabine show superior antitumor effects compared to gemcitabine alone in both orthotopic murine pancreatic cancer cell line grafts and in genetically engineered mouse models. Thus, the investigators propose a clinical trial of ibrutinib plus the standard gemcitabine based regimen of gemcitabine and nab-paclitaxel, evaluating safety, then efficacy and including correlative studies.

Detailed description public domain (ClinicalTrials.gov)

Pancreatic adenocarcinoma (PDAC) represents the fourth leading cause of cancer-related mortality in the United States, with an estimated 39,950 deaths attributable to PDAC in 2014 (http://seer.cancer.gov/statfacts/html/pancreas.html). Over 90% of patients have inoperable disease at presentation, at which point systemic therapy becomes the primary form of treatment. Treating PDAC has been challenging and few approved drugs are available. Recently, however, some breakthroughs have occurred, raising hope that this aggressive disease can be better controlled. FOLFIRINOX, a combination of 5FU, oxaliplatin, and irinotecan, has been found to be substantially superior to treatment of gemcitabine alone in patients with metastatic disease and good performance status. Similarly, gemcitabine and nab-paclitaxel, a regimen with less non-hematologic toxicity, demonstrated improved overall survival and progression-free survival compared to gemcitabine alone. Both of these combinations or modifications of these combinations are now front line options for patients with good performance status. Furthermore, these improvements in survival, however incremental, now afford patients with pancreatic cancer time to participate in and possibly benefit from clinical trials of novel therapeutics.

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

Number of Patients Who Experienced a Dose-Limiting Toxicity (DLT) [Up to 2 years]. Number, participants. Dose Escalation for Safety and Toxicity (n=10): 9; Immune Response Cohort (n=8): 8.

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

Maximum Tolerated Dose (MTD) [Up to 2 years]. Number, mg/day. Dose Escalation for Safety and Toxicity (n=10): 820; Immune Response Cohort (n=8): 560.

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

CA19-9 Clinical Response Rate [12 months]. Number, proportion of responders (95% Confidence Interval). Dose Escalation for Safety and Toxicity (n=6): 0.333 (0.0433 to 0.7772); Immune Response Cohort (n=7): 0.143 (0.0036 to 0.5787).

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

Median Time-to-progression (TTP) [10 months]. Median, days (95% Confidence Interval). Dose Escalation for Safety and Toxicity (n=10): 128 (56 to NA) [The upper range of the confidence interval was calculated to be infinity]; Immune Response Cohort (n=8): 126 (64 to NA) [The upper range of the confidence interval was calculated to be infinity].

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

Median Overall Survival (OS) [Up to 2 years]. Median, days (95% Confidence Interval). Dose Escalation for Safety and Toxicity (n=10): 246 (84 to NA) [The upper range of the confidence interval was calculated to be infinity]; Immune Response Cohort (n=8): 170 (66 to NA) [The upper range of the confidence interval was calculated to be infinity].

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

Median Progression-free Survival (PFS) [10 months]. Median, days (Full Range). Dose Escalation for Safety and Toxicity (n=10): 128 (56 to NA) [The upper range of the confidence interval was calculated to be infinity]; Immune Response Cohort (n=8): 99 (64 to NA) [The upper range of the confidence interval was calculated to be infinity].