Clinical trial NCT02039336: Dacomitinib Plus PD-0325901 in Advanced KRAS Mutant NSCLC
Official title: Phase I/II Study With the Combination of Dacomitinib and PD-0325901 in Metastatic KRAS Mutation Positive Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2014-01-17
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence rate of dose-limiting toxicities
timeFrame: 1.5 years
measure: Progression free survival
timeFrame: 2.5 years
Secondary outcomes:
measure: Incidence and severity of adverse events
timeFrame: 2.5 years
measure: Plasma concentration
timeFrame: 2.5 years
measure: Overall response rate
timeFrame: 2.5 years
measure: Duration of response
timeFrame: 1.5 years
measure: Time to response
timeFrame: 2.5 years
measure: Overall survival
timeFrame: 3 years
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center Cancer Institute
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: The Netherlands Cancer Institute
name: f opdam, MD, PhD
role: STUDY_DIRECTOR
affiliation: Erasmus Medical Centre Cancer Institute
name: FALM Eskens, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: UMC Utrecht
name: MPJK Lolkema, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Geel RMJM, van Brummelen EMJ, Eskens FALM, Huijberts SCFA, de Vos FYFL, Lolkema MPJK, Devriese LA, Opdam FL, Marchetti S, Steeghs N, Monkhorst K, Thijssen B, Rosing H, Huitema ADR, Beijnen JH, Bernards R, Schellens JHM. Phase 1 study of the pan-HER inhibitor dacomitinib plus the MEK1/2 inhibitor PD-0325901 in patients with KRAS-mutation-positive colorectal, non-small-cell lung and pancreatic cancer. Br J Cancer. 2020 Apr;122(8):1166-1174. doi: 10.1038/s41416-020-0776-z. Epub 2020 Mar 9.