NCT02039336

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
35

participants targeted

Target at P25-P50 for phase_1 colorectal-cancer

Timeline
Completed

Started Apr 2014

Typical duration for phase_1 colorectal-cancer

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 15, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 17, 2014

Completed
3 months until next milestone

Study Start

First participant enrolled

April 2, 2014

Completed
4.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 7, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 7, 2018

Completed
Last Updated

July 8, 2025

Status Verified

July 1, 2025

Enrollment Period

4.4 years

First QC Date

January 15, 2014

Last Update Submit

July 2, 2025

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

  • Incidence rate of dose-limiting toxicities

    1.5 years

  • Progression free survival

    2.5 years

Secondary Outcomes (6)

  • Incidence and severity of adverse events

    2.5 years

  • Plasma concentration

    2.5 years

  • Overall response rate

    2.5 years

  • Duration of response

    1.5 years

  • Time to response

    2.5 years

  • +1 more secondary outcomes

Study Arms (1)

Dacomitinib + PD-0325901

EXPERIMENTAL

Dacomitinib: oral tablets PD-0325901: oral capsules

Drug: DacomitinibDrug: PD-0325901Drug: Docetaxel

Interventions

DacomitinibDRUG
Dacomitinib + PD-0325901
PD-0325901DRUG
Dacomitinib + PD-0325901
DocetaxelDRUG
Dacomitinib + PD-0325901

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

The Netherlands Cancer Institute

Amsterdam, 1066CX, Netherlands

Location

Erasmus Medical Center Cancer Institute

Rotterdam, 3015CE, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584CX, Netherlands

Location

Related Publications (1)

  • 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.

    PMID: 32147669DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

dacomitinibmirdametinibDocetaxel

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenes

Study Officials

  • f opdam, MD, PhD

    The Netherlands Cancer Institute

    STUDY DIRECTOR

  • FALM Eskens, PhD

    Erasmus Medical Centre Cancer Institute

    PRINCIPAL INVESTIGATOR

  • MPJK Lolkema, PhD

    UMC Utrecht

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 15, 2014

First Posted

January 17, 2014

Study Start

April 2, 2014

Primary Completion

August 7, 2018

Study Completion

August 7, 2018

Last Updated

July 8, 2025

Record last verified: 2025-07

Locations

NL(3)