Phase I/II study with lapatinib plus trametinib in patients with metastaticnon-small cell lung cancer with a mutation in the KRAS gene

Phase 1

• Conditions: non-small cell lung cancer; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-002209-39-NL
• Lead Sponsor: The Netherlands Cancer Institute

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-06-17
• Last Update Posted: 3 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 132

Inclusion Criteria

1.Histological or cytological proof of metastatic NSCLC ; for PART B: treated with first line therapy for metastatic disease only.
2.Written documentation of a known pathogenic KRAS (exon 2, 3 or 4) mutation and PIK3CA wild-type (exon 9 and 20).
3.Age = 18 years.
4.Able and willing to give written informed consent.
5.WHO performance status of 0 or 1 (part A and B)
6.Able to swallow and retain orally administered medications and does not have clinically significant gastrointestinal abnormalities that may alter absorption (e.g. malabsorption syndrome or major resection of the stomach or bowel)
7.Able and willing to undergo blood sampling for PK and PD analysis.
8.Able and willing to undergo a tumor biopsy prior to start, after two weeks on therapy and upon progression of disease

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32

Exclusion Criteria

1.Any treatment with investigational drugs within 30 days prior to receiving the first dose of investigational treatment.
2.History of another primary malignancy
3.Symptomatic or untreated leptomeningeal disease.
4.Symptomatic brain metastasis. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid and anticonvulsant therapy (for at least 6 weeks) are allowed to enrol. Radiotherapy for brain metastasis must have been completed at least 6 weeks prior to start of study treatment. Brain metastasis must be stable with verification by imaging (e.g. brain MRI or CT completed at screening demonstrating no current evidence of progressive brain metastases). Patients are not permitted to receive anti-epileptic drugs or corticosteroids.
5.Patients previously treated with any targeted drug combination known to interfere with EGFR, HER-2, HER-3, HER-4 or MAPK- and PI3K-pathway components, including inhibitors of PI3K, AKT, mTOR, BRAF, MEK and ERK.
6.History of interstitial lung disease or pneumonitis

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified