non-small cell lung cancer
Conditions
Interventions
Product Name: Lapatinib
Pharmaceutical Form: Tablet
INN or Proposed INN: LAPATINIB
CAS Number: 231277-92-2
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 500-1500
Sponsors
The Netherlands Cancer Institute
Eligibility
Sex/Gender
All
Inclusion criteria
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the recommended phase 2 dose (RP2D) of the lapatinib- trametinib combination in patients with KRASm NSCLC To determine the progression free survival of the lapatinib-trametinib combination compared to standard of care therapy in patients with KRASm NSCLC;Secondary Objective: - To characterize the safety and tolerability of lapatinib in combination with trametinib. - To asses anti-tumor activity of lapatinib in combination with trametinib. - To determine the pharmacokinetic profile of lapatinib and trametinib in this combination. - To explore genetic determinants of response to the lapatinib-trametinib combination - To explore the potential mechanism of resistance to lapatinib in combination with trametinib, as measured by gene alterations/expression profiles (baseline, relapse) in tumor tissue upon progression;Primary end point(s): Incidence of dose-limiting toxicities (DLTs) Progression free survival (PFS) per RECIST version 1.1;Timepoint(s) of evaluation of this end point: Continuous Every 8 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Incidence and severity of adverse events Overall response rate, duration of response, time to response and overall survival (phase II only) Plasma concentrations of lapatinib, trametinib and relevant metabolites Baseline molecular status of potential predictive markers of tumor response (BRAF, HRAS, KRAS, NRAS, PTEN, PIK3CA, MAPK1, MAPK2, ARAF, c-MET, EGFR etc.) Gene alteration (baseline, relapse) in tumor tissue;Timepoint(s) of evaluation of this end point: Continuous Every 8 weeks / continuous Cycle 1 Day 1, 2, Cycle 2 Day 1, 2, Day 1 of subsequent cycles Baseline Baseline, on treatment, and upon progressive disease | — |
Countries
Netherlands
Contacts
Public ContactCarla Vianen
The Netherlands Cancer Institute
Outcome results
None listed