A clinical trial to study the effect of Capmatinib in Indian patients with Metastatic NSCLC (MET exon 14 skipping mutation positive)
- Conditions
- Health Condition 1: C349- Malignant neoplasm of unspecifiedpart of bronchus or lung
- Registration Number
- CTRI/2022/05/042549
- Lead Sponsor
- ovartis Healthcare Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
1. Signed informed consent must be obtained prior to participation in the study.
2. Adult more than or equal to 18 years old at the time of informed consent.
3.Metastatic NSCLC (Stage IV, according to Version 8 of the AJCC Staging Manual) either treatment naïve or progressed (clinically and/or radiologically) on one or more lines of systemic therapy.
4. Histologically or cytologically confirmed diagnosis of NSCLC with confirmed
EGFR wild type and ALK rearrangement negative and who have tested positive MET
exon14 skipping mutation Locally available MET report either by reverse
transcriptase polymerase chain reaction RTPCR or NGS would be considered in
case not available MET testing would be done through NGS based molecular prescreening
done as part of the study.
5. Patients must have recovered from all toxicities related to prior systemic therapies to
grade less than or equal to 1 Common Terminology Criteria for Adverse Events CTCAE version 5.0.
6. At least one measurable lesion as defined by RECIST 1.1.
7. Patients must have adequate organ function including the following laboratory values at the screening visit.
a. Absolute neutrophil count more than or equal to 1.5 x 109/L without growth factor support
b. Platelets more than or equal to 100 x 109/L
c. Hemoglobin more than or equal to 9 g/dL
d. Calculated creatinine clearance using Cockcroft Gault formula more than or equal to 45 mL/min
e. Total bilirubin less than or equal to 1.5 ULN upper limit of normal except in patients with Gilberts syndrome who may be included if total bilirubin is less than or equal to 3.0 x ULN and direct bilirubin is less than or equal to 1.5 x ULN
f. AST less than or equal to 3 x ULN except for patients with liver metastasis, who may only be included if AST less than or equal to 5 x ULN
g. ALT less than or equal to 3 x ULN except for patients with liver metastasis who may only be included if ALT less than or equal to 5 x ULN
h.Alkaline phosphatase ALP less than or equal to 5.0 x ULN
i. Asymptomatic serum amylase less than or equal to grade 2. Patients with grade 1 or grade 2 serum amylase at the beginning of the study must be confirmed to have no signs and or symptoms suggesting pancreatitis or pancreatic injury e.g. elevated P amylase, abnormal imaging findings of pancreas etc.
j. Serum lipase less than or equal to ULN
8. Eastern Cooperative Oncology Group ECOG performance status PS of 0 to 2.
9. Willing and able to comply with scheduled visits treatment plan and laboratory tests.
1. Prior treatment with any MET inhibitor or hepatocyte growth factor targeting therapy.
2. Presence or history of a malignant disease other than NSCLC that has been
diagnosed and/or required therapy within the past 3 years. Exceptions to this
exclusion include the following: completely resected basal cell and squamous cell
skin cancers and completely resected carcinoma in situ of any type.
3. Patients 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.
4. Patients 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.
5. Presence or history of interstitial lung disease or interstitial pneumonitis, including
clinically significant radiation pneumonitis i.e. affecting activities of daily living or requiring therapeutic intervention.
6. Subject with clinically significant heart diseases like unstable angina acute
myocardial infraction within 6 months prior to screening, NYHA class III IV congestive cardiac failure uncontrolled hypertension, arrhythmias or QTcF more than or equal to 470 ms on the screening ECG.
7. Major surgery e.g. intra-thoracic intra-abdominal or intrapelvic within 4 weeks
prior 2 weeks for resection of brain metastases to starting capmatinib or who have
not recovered from side effects of such procedure. Video-assisted thoracic surgery
and mediastinoscopy will not be counted as major surgery and patients can be
enrolled in the program more than or equal to 1 week after the procedure.
8. Thoracic radiotherapy to lung fields less than or equal to 4 weeks prior to starting capmatinib or patients who have not recovered from radiotherapy-related toxicities. For all other anatomic sites including radiotherapy to thoracic vertebrae and ribs radiotherapy less than or equal to 2 weeks prior to starting capmatinib or patients who have not recovered from radiotherapyrelated toxicities. Palliative radiotherapy for bone lesions less than or equal to 2 weeks prior to starting capmatinib is allowed.
9. Impairment of gastrointestinal GI function or GI disease that may significantly alter
the absorption of capmatinib or patients who are unable to swallow oral tablets.
10. Patients receiving treatment with strong inducers of CYP3A that cannot be
discontinued at least 1 week prior to the start of treatment with capmatinib and for the duration of the study.
11. Unable or unwilling to swallow tablets as per dosing schedule.
12. Patients with known hypersensitivity to capmatinib and any of the excipients of capmatinib.
13. Patients with any other severe, acute or chronic medical or psychotic conditions or
significant abnormal physical findings 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.
14. Patients with prior systemic anti-cancer chemotherapy immunotherapy biologic
therapy vaccine and investigational agents within 4 weeks or less than or equal to 5 x half-life of the
agent whichever is shorter befo
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Incidence of AEs, including SAEs after <br/ ><br>treatment initiation, changes in laboratory <br/ ><br>values, vital signs, and ECGs <br/ ><br>Tolerability dose interruptions, reductions, <br/ ><br>and dose intensity. <br/ ><br>Timepoint: Baseline Week 1, Week 4, Week 7, Week 10, Week 13, Week 16, Week 19, Week 22, Week 24 (EOT), EOS (30 days after EOT) <br/ ><br>
- Secondary Outcome Measures
Name Time Method All assessed per RECIST 1.1 by <br/ ><br>investigator assessment <br/ ><br>• ORR <br/ ><br>• OIRR <br/ ><br>• DOR <br/ ><br>• TTR <br/ ><br>• DCR <br/ ><br>• PFSTimepoint: Every 6 weeks (±7 days) from the first day of treatment with capmatinib until disease progression or 24 weeks/6 months or EOS. <br/ ><br>