A prospective, multicenter, open-label, Phase IV, interventional study to assess the safety and efficacy of Capmatinib in Indian patients with mesenchymal-epithelial transition (MET) exon 14 skipping mutation positive metastatic non-small cell lung cancer (NSCLC)
OPD 7, Aadhar Health Institute, Tosham Road, Near South Bypass, Crossing Hisar, Haryana 125005 Hisar HARYANA
9896539142
drlovenish@gmail.com
Dr Deepam Pushpam
AIIMS
Room No 245, Department of Medical Oncology, Second Floor, Dr. B.R.A. Institute Rotary Cancer Hospital
Indian Institute of Medical Sciences, Sri Aurobindo Marg, Ansari Nagar East, New Delhi Delhi - 110029 East DELHI
9650629370
deepampushpam@gmail.com
Dr Sandip Barik
AIIMS
Department of Radiotherapy, Basement Hospital Building, Sijua, Patrapada, Bhubaneswar, 751019, Odisha Khordha ORISSA
Department of Medical Oncology,
Chittaranjan National Cancer Institute,
37, SP Mukherjee Road,
Kolkata-700026, India Kolkata WEST BENGAL
9830115905
kkmukherjee4u@hotmail.com
Dr Minish Jain
CIMET’s Inamdar Multispeciality Hospital
CIMET’s Inamdar Multispeciality Hospital,
Building Sr. No: 15, Behind KPCT Mall, Fatima Nagar, Wanawadi, Pune-411040, Maharashtra, India. Pune MAHARASHTRA
9823133390
minishjain009@gmail.com
Dr Dinesh Shet
Father Muller Medical College Hospital
"Depart of Medical Oncology,
Father Muller Medical College Hospital
Father Muller Road, Kankanady, Mangalore,
Karnataka - 575002, India"
Dakshina Kannada KARNATAKA
7259606348
shetdinesh@yahoo.co.in
Dr Abdul Majeed
Government Medical College
Department of General Medicine, Division of Medical Oncology & Hematology, Kozhikode 673008, Kerala Kozhikode KERALA
9447311247
majeedonco@gmail.com
Dr Koushik Chatterjee
IPGMER and SSKM Hospital
244, Acharya J. C. Bose Road, Kolkata West,
Bengal 700020, India
Kolkata WEST BENGAL
9874357580
drkoushik.chatterjee@gmail.com
Dr Prasanth Ganesan
Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER)
Department of Medical Oncology,
3rd Floor, Super Speciality Building, Gorimedu, Dhanvantri Nagar, Puducherry - 605006 Pondicherry PONDICHERRY
9444216310
pg1980@gmail.com
Dr Srikant Tiwari
Jawaharlal Nehru Cancer Hospital And Research Centre
P.B No. 32, Cancer Hospital Road, Idgah Hills, Bhopal Madhya Pradesh 462001 Bhopal MADHYA PRADESH
Department of Medical Oncology, OPD No. 28, MPMMCC Sundarpur, Varanasi 221005, Uttarpradesh Varanasi UTTAR PRADESH
7597364554
kapoorakhil1987@gmail.com
Dr Praveen Kumar Shenoy V P
Malabar Cancer Centre
Department of Clinical Haematology & Medical Oncology, Moozhikkara P.O, Kodiyeri, Thalassery, Kannur, Kerala, 670103 India Kannur KERALA
9790463281
vppraveen233@gmail.com
Dr P K Chaithanya
MNJ Institute of Oncology & Regional Cancer Centre
Red Hills, Lakdikapul, Hyderabad, Telangana-500004 Hyderabad TELANGANA
8897199994
mnjiorccchaithanya@gmail.com
Dr Udip Dilip Maheswari
Mumbai Oncocare Centre (Unit of Cellcure Cancer Centre Pvt Ltd)
Mumbai Oncocare Centre (Unit of Cellcure Cancer Centre Pvt Ltd)
1 to 4, 1st floor, Shreepati Arcade,
August Kranti Rd, Nana Chowk,
Kemps Corner, Grant Road,
Mumbai-400036. Maharashtra India. Mumbai MAHARASHTRA
7677434237
drudipdm@mocindia.co.in
Dr Anand Pathak
National Cancer Institute (NCI)
Khasra No 25, Outer Hingna Ring Road, Mouza-Jamtha Nagpur - 441108. Maharashtra Nagpur MAHARASHTRA
9823038498
medical_director@ncinagpur.in
Dr Sadashivudu Gundeti
Nizams Institute of Medical Sciences
Department of Medical Oncology, Punjagutta Market, Punjagutta, Hyderabad, Telangana,
India 500082
Hyderabad TELANGANA
Aadhar institutional Ethics committee, AADHAR HEALTH INSTITUTE, Tosham Road, Near South Bypass Crossing Hisar, Haryana 125005, India
Approved
Ethics Committee Inamdar Multispeciality Hospital CIMETs Inamdar Multispeciality Hospital, Building S.No. 15, Fatima Nagar, Wanawadi, Pune, Maharashtra-411040 India
Approved
Father Muller Institutional Ethics Committee
Approved
GCRI GCS Ethics Committee, The Gujarat Cancer and Research Institute, Civil Hospital Campus, Asarwa, Ahmedabad, Gujarat 380016, India
Approved
Human Ethics Committee, RCC Regional Cancer Centre Medical College Campus, Thiruvananthapuram, Kerala 695011, India
Approved
IEC MPMMCC and HBCH Varanasi, Mahamana Pandit Madan Mohan Malaviya Cancer Centre, Sundar Bagiya, Near Nariya Gate Banaras, Hindu University Campus, Varanasi, Uttar Pradesh 221005, India
Approved
IEC Intervention Studies JIPMER
Approved
IEC Malabar Cancer Centre, Moozhikkara P O, Kodiyeri, Thalassery, Kannur, Kerala 670103, India
Approved
Institute Ethics Committee All India Institute of Medical Sciences, New Delhi
Approved
INSTITUTE ETHICS COMMITTEE for clinical Trials AIIMS, Nagpur
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Institute Ethics Committee, All India Institute of Medical Sciences, Raipur, Chattisgarh
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INSTITUTIONAL ETHICS COMMITTEE AlIMS, All India Institute of Medical Sciences BBSR, Bhubaneswar Sijua, P O Patrapada, Bhubaneswar, Khordha Orissa 751019, India
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Institutional Ethics Committee Bhagwan Mahaveer Cancer Hospital and Research Center
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Institutional Ethics Committee Chittaranjan National Cancer Institute
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Institutional Ethics Committee MNJ Institute of Oncology & Regional Cancer Centre
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Institutional Ethics Committee Sparsh Hospitals Sparsh Hospitals & Critical Care (P) Ltd. Plot no. A/407, Saheed Nagar, Bhubaneswar-751007, Odisha, India
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Institutional Ethics Committee VMMC and SJH VMMC And SAFDARJUNG HOSPITAL
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Institutional Ethics Committee, Government Medical College, 4th Floor, Golden Jubilee Annex Institute of Maternal and Child Health Kozhikode, Kerala 673008, India
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Institutional Ethics Committee, North East Cancer Hospital and research institute, 11th mile, Amerigog, Jorabat, Guwahati, Kamrup Metropolitan, Assam 781023, India
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IPGMER and Research Oversight Committee, IPGMER, 244, Acharya J C Bose Road, Kolkata, West Bengal 700020, India
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JNCHRC, PO Box No 32, Idgah Hills Bhopal, Madhya Pradesh 462001 India
Mumbai Oncocare Centre Institutional Ethics Committee 1 to 4, 1st floor, Shreepati Arcade, August Kranti Rd, Nana Chowk, Kemps Corner, Grant Road, Mumbai-400036. Maharashtra India.
Approved
National cancer Institute Ethics Committee
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NIEC NIMS Institutional Ethics Committee, Nozams Institute of Medical Sciences, Panjagutta, Hyderabad, Telangana, India 500082
Approved
TMH Institutional Ethics Committee-I Tata Memorial Hospital
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.
ExclusionCriteria
Details
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 before first dose of capmatinib. If previous treatment is
a monoclonal antibody then the treatment must be discontinued at least 4 weeks
before first dose of capmatinib. If previous treatment is an oral targeted agent, then
the treatment must be discontinued at least 5 x half-life of the agent.
15. Pregnant or nursing (lactating) women.
16. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
while taking study treatment and for 7 days after stopping study treatment. Highly
effective contraception methods include:
a. Total abstinence when this is in line with the preferred and usual lifestyle of the
patient. Periodic abstinence e.g. calendar, ovulation, symptothermal, postovulation
methods and withdrawal are not acceptable methods of contraception.
b. Female sterilization have had surgical bilateral oophorectomy with or without
hysterectomy total hysterectomy or bilateral tubal ligation 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 followup hormone level
assessment.
c. Male sterilization at least 6 months prior to screening. For female patients on the
study, the vasectomized male partner should be the sole partner for that patient.
d. Use of oral estrogen and progesterone injected or implanted hormonal methods
of contraception or placement of an intrauterine device or intrauterine system, or
other forms of hormonal contraception that have comparable efficacy failure rate
less than or equal to 1% for example hormone vaginal ring or transdermal hormone contraception.
In case of use of oral contraception women should have been stable on the same
pill for a minimum of 3 months before taking treatment.
17. Sexually active males unwilling to use a condom during intercourse while taking
study treatment and for 7 days after stopping study treatment. A condom is required
for all sexually active male patients to prevent them from fathering a child AND to
prevent delivery of study treatment via seminal fluid to their partner. In addition male
patients must not donate sperm for the time period specified above.
18. Any other condition that would in the Investigator judgment contraindicate
patient’s participation in the clinical study due to safety concerns or compliance with
clinical study procedures e.g. active infection including active hepatitis B and C
SARS CoV2 inflammation intestinal obstruction unable to swallow medication
Social or psychological issues etc.
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
Incidence of AEs, including SAEs after
treatment initiation, changes in laboratory
values, vital signs, and ECGs
Tolerability dose interruptions, reductions,
and dose intensity.
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)
Secondary Outcome
Outcome
TimePoints
All assessed per RECIST 1.1 by
investigator assessment
• ORR
• OIRR
• DOR
• TTR
• DCR
• PFS
Every 6 weeks (±7 days) from the first day of treatment with capmatinib until disease progression or 24 weeks/6 months or EOS.
Target Sample Size
Total Sample Size="50" Sample Size from India="50" Final Enrollment numbers achieved (Total)= "50" Final Enrollment numbers achieved (India)="50"
This is a Phase IV, prospective, multicenter, open-label, interventional study to assess the safety and efficacy of capmatinib in Indian patients with MET exon 14 skipping mutation positive metastatic NSCLC in any line of therapy. The study will include molecular prescreening 28 days for patients who do not have documented MET exon 14 skipping mutation positive results screening period 28 days treatment period of 24 weeks 6 months, 400 mg BID treatment as continuation dosing end of treatment EOT visit and follow-up period of 30 days post last dose of study treatment. Completion of the followup period after the last dose of the study treatment will be considered as the End of Study EOS. Patients transitioning to PTA will also have to compete the EOS Visit assessment after the last dose administration of capmatinib which is as a part 6 months of treatment for the current study. The total study duration for 50 patients in the study will be approximately 2.5 years. The study will include approximately 50 Indian patients. During screening period patients will undergo screening procedures for meeting the eligibility for the study During the treatment phase, treatment will be administered as capmatinib 400 mg orally BID on a continuous dosing schedule for the duration of 24 weeks 6 months. Followup period of 30 days include safety evaluations after end of the study treatment. Completion of the follow-up period will be considered as the End of Study EOS.