A Randomized Multi-center Phase I/II Trial of ICM (Irinotecan, Cisplatin, Mitomycin C) With or Without AZD2281 (Olaparib) in Patients With Advanced Pancreatic Cancer
The trial is designed to evaluate the role of Parp inhibitor based therapy, combining the
most well studied and potent Parp inhibitor currently available with a low-dose combination
of DNA damaging agents to optimize the effects of Parp inhibition. To ensure optimal
response rates in the trial, to enrich our population for patients likely to achieve the
best clinical response to Parp inhibitor based therapy, we will recruit and enroll patients
with known BRCA mutations, patients of Jewish ancestry, patients with familial pancreatic
cancer, as well as with sporadic pancreatic cancer. We will test patients and their cancers
for other inherited or acquired defects in homologous DNA repair. For the phase 1 study, we
will enroll up to 30 patients. For the phase 2 component of the study, 100 patients with
locally, advanced, unresectable or metastatic pancreatic cancer will be enrolled. An initial
phase I analysis will be performed to test the safety of the ICM with Olaparib regimen at
the doses we predict will be effective for the phase 2 and ensure that these doses are below
the maximum tolerated dose. For this phase 1 we will use a standard 3+3 design and will test
the following dose regimens in a 28 day cycle:
Dose level 1: Cisplatin/Irinotecan i.v.(day 1, 8) and Olaparib (100 mg bid p.o., Day 1 & Day
8) Dose level 2: Cisplatin/Irinotecan i.v.(day 1, 8) and Olaparib 100 bid p.o. day 1-3, day
8-10 (if this dose is not tolerated, go to Dose 5: Mitomycin + Olaparib Dose level 1) Dose
level 3: Cisplatin/Irinotecan i.v.(day 1, 8) and Olaparib 200 bid p.o.day 1-3, day 8-10 (if
this dose is not tolerated, go to Dose 5: Mitomycin + Olaparib Dose level 2) Dose level 4:
Cisplatin/Irinotecan i.v.(day 1, 8) and Olaparib 200 bid p.o. day 1-12 (if this dose is not
tolerated, go to Dose 5: Mitomycin + Olaparib Dose level 3)) Dose level 5:
Cisplatin/Irinotecan i.v.(day 1, 8), Mitomycin Day 1 (5 mg/m2 IV), along with the
established tolerated dose level of Olaparib.
Other intermediate dose schedules of Olaparib may be considered to achieve the most optimal
tolerable regimen" If there are DLTs at Dose 1, we will reduce the duration of Olaparib
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
The number of Participants with Adverse Events and the severity of these adverse events as a Measure of Safety and Tolerability.
Phase I - Assess the safety and toxicities of IC with Olaparib escalating to ICM with Olaparib in patients with locally advanced and metastatic pancreatic cancer and determine the phase 2 dose. Phase II - Assessment of the objective response rates (ORR) of patients with locally advanced and/or metastatic pancreatic cancer treated with IC/ICM with placebo vs. IC/ICM with Olaparib.
1 year
Yes
Michael Goggins, MD
Principal Investigator
Sol Goldman Pancreatic Cancer Research Center, JHMI
United States: Food and Drug Administration
J1070
NCT01296763
January 2011
January 2016
Name | Location |
---|---|
Columbia University Medical Center | New York, New York 10032 |
The Johns Hopkins University School of Medicine | Baltimore, Maryland 21231 |