Dacomitinib Plus PD-0325901 in Advanced KRAS Mutant NSCLC

Phase 1

• Conditions: Colorectal Cancer
• Interventions: Drug: Dacomitinib; Drug: PD-0325901; Drug: Docetaxel

• Registration Number: NCT02039336
• Lead Sponsor: The Netherlands Cancer Institute

Brief Summary

This is a phase I/II multi-center open-label proof of concept study, consisting of two parts. Part A of this study is designed to identify the recommended phase 2 dose (RP2D) of the combination regimen of dacomitinib plus PD-0325901 in patients with advanced KRAS mutant (KRASm) non-small cell lung cancer (NSCLC). Part B is designed to perform a randomized comparison of the combination of dacomitinib and PD-0325901 versus standard of care therapy in patients with advanced KRASm NSCLC. It is hypothesized that with this combination strategy the progression free survival of patients with KRASm NSCLC will be doubled.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-01
• Study First Submitted: 2014-01-15
• Study First Submitted QC: 2014-01-15
• Study First Posted: 2014-01-17
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-24
• Last Update Posted: 2018-08-27
• Primary Completion: 2018-12
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

• Histological or cytological proof of advanced non-small cell lung cancer
• Written documentation of KRAS (exon 2, 3 or 4) mutation
• At least 18 years of age or older
• Able and willing to give written informed consent
• WHO performance status of 0 or 1

Exclusion Criteria

• Symptomatic or untreated leptomeningeal disease
• Symptomatic brain metastasis
• Impairment of gastrointestinal function
• Uncontrolled infectious disease
• Left ventricular ejection fraction < 50%
• Retinal degenerative disease or with history of uveitis, retinal vein occlusion or retinal detachment

Other protocol-defined inclusion/exclusion criteria may apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dacomitinib + PD-0325901	Dacomitinib	Dacomitinib: oral tablets PD-0325901: oral capsules
Dacomitinib + PD-0325901	Docetaxel	Dacomitinib: oral tablets PD-0325901: oral capsules
Dacomitinib + PD-0325901	PD-0325901	Dacomitinib: oral tablets PD-0325901: oral capsules

Primary Outcome Measures

Name	Time	Method
Incidence rate of dose-limiting toxicities	1.5 years
Progression free survival	2.5 years

Secondary Outcome Measures

Name	Time	Method
Duration of response	1.5 years
Time to response	2.5 years
Plasma concentration	2.5 years
Overall response rate	2.5 years
Incidence and severity of adverse events	2.5 years
Overall survival	3 years

Trial Locations

Locations (3)

Erasmus Medical Center Cancer Institute; 🇳🇱 Rotterdam, Netherlands

The Netherlands Cancer Institute; 🇳🇱 Amsterdam, Netherlands

University Medical Center Utrecht; 🇳🇱 Utrecht, Netherlands