Phase IB/Randomized Phase II Study of Folfirinox Plus AMG-479 (Ganitumab) or Placebo in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma
OBJECTIVES:
Primary
- To assess the safety and determine the maximally tolerated dose (MTD) of modified
FOLFIRINOX (mFOLFIRINOX) and ganitumab in patients with previously untreated,
metastatic pancreatic adenocarcinoma. (phase I)
- To compare overall survival of patients with previously untreated, metastatic
pancreatic adenocarcinoma who receive mFOLFIRINOX plus ganitumab versus mFOLFIRINOX
plus placebo. (phase II)
- To assess the convergent validity of each selected PRO-CTCAE item by comparing each
item at baseline between patients with ECOG performance status (PS) 0 vs 1. (phase II)
Secondary
- To compare objective response rate, duration of response, and progression-free survival
of patients with previously untreated, metastatic pancreatic adenocarcinoma who receive
mFOLFIRINOX plus ganitumab versus mFOLFIRINOX plus placebo.
- To compare treatment-related toxicity in patients with previously untreated, metastatic
pancreatic adenocarcinoma who receive mFOLFIRINOX plus ganitumab versus mFOLFIRINOX
plus placebo.
- To assess the responsiveness (sensitivity to change) of Patient-Reported Outcomes
(PRO)-CTCAE by comparing change scores within groups of patients as defined by changes
in ECOG PS at post-baseline administrations. (phase II)
- To compare the maximum post-baseline score for each PRO-CTCAE item per patient between
arms in the randomized phase II component of the study. (exploratory).
OUTLINE: This is a dose-escalation, phase IB study followed by a randomized phase II study.
Patients in the phase II study are stratified according to ECOG performance status of 0
versus 1.
- Phase IB: Patients receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV
over 90 minutes, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV
over 48 hours beginning on day 2 (mFOLFIRINOX). After cohort 0, subsequent patients
also receive ganitumab IV over 1 hour on day 1. Treatment repeats every 14 days in the
absence of disease progression or unacceptable toxicity.
- Phase II: Patients are randomized to 1 of 2 treatment arms:
- Arm I: Patients receive mFOLFIRINOX as in Phase IB and ganitumab IV over 30-60
minutes on day 1.
- Arm II: Patients receive mFOLFIRINOX as in Phase IB and placebo IV over 30-60
minutes on day 1.
In both arms, treatment repeats every 14 days in the absence of disease progression or
unacceptable toxicity.
Patients randomized in the phase II component of the study may complete 16 Patient-Reported
Outcomes (PRO)-CTCAE items (measuring 8 symptoms) on paper on day 1 of all odd-numbered
courses (i.e., courses 1, 3, 5, etc.).
Tumor tissue and blood samples may be collected for correlative studies.
After completion of study therapy, patients are followed every 3 months for 3 years.
Interventional
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicity (phase I)
Yes
Brain M. Wolpin, MD
Principal Investigator
Dana-Farber Cancer Institute
United States: Food and Drug Administration
CDR0000716301
NCT01473303
August 2012
Name | Location |
---|