AZD8931, an Inhibitor of EGFR, ERBB2 and ERBB3 Signalling, in Combination With FOLFIRI: a Phase I/II Study to Determine the Importance of Schedule and Activity in Colorectal Cancer
PANTHER is a registered phase I/randomised phase II trial in patients with recurrent or
metastatic colorectal cancer. Patients are recruited to received AZD8931 (an EGFR/ERBB
inhibitor) in combination with FOLinic acid, Fluorouracil and IRInotecan (FOLFIRI). AZD8931
and FOLFIRI will be given in two-weekly cycles. The Phase I trial will aim to determine the
recommended Phase II dose of AZD8931 (either 20, 40, 80 or 160mg bd, on days 1-4 of each
2-weekly cycle) - the dose of AZD8931 that patients will receive will depend on the dose
under investigation at the time of registration.
The AZD8931 dose will be determined by the Modified Continual Reassessment Method (mCRM).
mCRM is a dose-toxicity model which describes the probability of a toxicity occurring at
each dose level, which is based on clinical judgment and any available toxicity data.
The recommended AZD8931 dose in combination with FOLFIRI, determined from the phase I trial,
will become one of the treatment groups in the randomised Phase II - the other treatment
group will be FOLFIRI alone (Control group).
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Occurrence of Dose Limiting Toxicity
Detailed adverse event monitoring will be conducted according to CTCAE v4.03. Dose Limiting Toxicity (DLT) is defined as any adverse event or laboratory abnormality detailed in the trial protocol, that is considered to be related to AZD8931 and commencing anytime during the DLT evaluation period (from start of cycle 1 to end of cycle 1). Adverse Events include: Skin, Gastrointestinal, Haematological, Clinical Chemistry, Cardiovascular.
From start of cycle 1 to end of cycle 1 (each cycle = 2 weeks)
Daniel Hochhauser, BA, MBBS, MRCP, D.PHIL, FRCP
University College London (UCL) Cancer Institute
United Kingdom: Medicines and Healthcare Products Regulatory Agency