Phase I/II study with lapatinib plus trametinib in patients with metastatic KRAS mutant non-small cell lung cancer
- Conditions
- non-small cell lung cancer10038666
- Registration Number
- NL-OMON46994
- Lead Sponsor
- Antoni van Leeuwenhoek Ziekenhuis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 132
1. Histological or cytological proof of metastatic NSCLC;
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
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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Incidence of dose-limiting toxicities (DLTs) Progression free survival (PFS)<br /><br>per RECIST version 1.1</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Incidence and severity of adverse events<br /><br>- Overall response rate<br /><br>- Duration of response<br /><br>- Time to response<br /><br>- Overall survival (phase II only)<br /><br>- Plasma concentrations of lapatinib, trametinib and relevant metabolites<br /><br>- Baseline molecular status of potential predictive markers of tumor response<br /><br>(BRAF, HRAS, KRAS, NRAS, PTEN, PIK3CA, MAPK1, MAPK2, ARAF, c-MET, EGFR etc.)<br /><br>- Gene alteration (baseline, relapse) in tumor tissue</p><br>