Study of efficacy of capmatinib in comparison with standard of care docetaxel as a second or third line therapy in participants with non-small cell lung cancers harboring MET exon 14 skipping mutation.
- Conditions
- cMET mutated NSCLCMedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-001578-31-NL
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 90
1. Signed informed consent must be obtained prior to participation in the study.
2. Adult = 18 years old at the time of informed consent.
3. Stage IIIB/IIIC (not amenable to surgery, radiation or multi modality therapy) or IV NSCLC at the time of study entry.
4. Histologically or cytologically confirmed diagnosis of NSCLC that is:
• EGFR wt. This should have been assessed as part of the participant’s standard of care by a validated test for EGFR mutations as per local guidelines.
• AND has MET?ex14 mutation as determined by Novartis-designated central laboratory or by locally performed, tissue-based test, validated according to local regulation, from a Clinical Laboratory Improvement Amendments (CLIA)-certified US laboratory or an accredited local laboratory outside of the US. The positive MET?ex14 mutation result as determined per local test must be documented in the participant's source documents and in the CRF prior to entering main screening.
5. Mandatory provision of a formalin-fixed, paraffin embedded tumor tissue sample (archival tumor block or slides, or a newly obtained tumor sample) with quality and quantity sufficient to allow assessment of MET ?ex14 mutation status (as defined in the study [laboratory manual]). This pertains to all participants, including those who have a MET ?ex14 mutation result from a local test. Tumor samples must contain at least 10% tumor content.
6. Participants must have progressed on one or two prior lines of systemic therapy for advanced/metastatic disease (stage IIIB/IIIC [not candidates for surgery, radiation or multi modality therapy] or IV NSCLC), and must be docetaxel naive and candidates for single agent chemotherapy (docetaxel). Treatment failure is defined as documented disease progression or intolerance to treatment, however participants must have progressed on or after the last therapy before study entry.
7. ECOG performance status (PS) of 0 - 1.
8. Participants must have a life expectancy of at least 3 months.
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 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 54
1. Prior treatment with any MET inhibitor or HGF-targeting therapy.
2. Participants with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms. If participants are on corticosteroids for endocrine deficiencies or tumor-associated symptoms other than CNS related, dose must have been stabilized (or decreasing) for at least 5 days before Cycle 1 Day 1.
3. Participants with known druggable molecular alterations (such as ROS1 translocation or BRAF mutation, etc.) which might be a candidate for alternative targeted therapies as applicable per local regulations and treatment guidelines.
4. Participants with known druggable molecular alterations (such as ROS1 and RET rearrangement, BRAF mutation, KRAS mutation, NTRK fusion, etc.) which might be a candidate for alternative targeted therapies.
5. Substance abuse, active infection or other severe, acute, or chronic medical or psychotic conditions or laboratory abnormalities that in the opinion of the investigator may increase the risk associated with study participation, or that may interfere with the interpretation of study results.
Active infections include but are not limited to Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV). Screening for known chronic conditions is not required. Participants with known serologic evidence of chronic HBV or HCV infection, whose disease is controlled under antiviral therapy, according to local regulations are eligible. Participants with known history of testing positive for human immunodeficiency virus (HIV)
infection, and with a history of acquired immunodeficiency syndrome
(AIDS)-defining opportunistic infections in the last 12 months prior to the first dose of study treatment must be excluded. HIV participants at high risk or with history of uncontrolled opportunistic infection must also be excluded. To ensure that effective anti-retroviral treatment (ART) is tolerated and that toxicities are not confused with investigational drug toxicities, trial
participants should be on established ART for at least four weeks prior to enrollment, they should have the disease under control and suppressed viral loads defined as per local guideline. HIV participants co-infected with hepatitis virus must also be excluded.
6. For female participants treated with docetaxel, a highly effective contraception must be used during the study. Local prescribing information relating the time limits for such precautions and any additional restrictions will be followed.
Highly effective contraception methods include:
- Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.
- Female bilateral tubal ligation, female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), or total hysterectomy at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.
- Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant.
- Use of oral (estrogen and
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method