| CTRI Number |
CTRI/2018/12/016591 [Registered on: 10/12/2018] Trial Registered Prospectively |
| Last Modified On: |
24/11/2022 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Biological |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
Safety of Pembrolizumab in advanced lung cancer or melanoma |
|
Scientific Title of Study
|
A Prospective, Open-label, Phase 4 Study to Evaluate the Safety of Pembrolizumab (KEYTRUDA®) in Subjects with Unresectable or Metastatic Melanoma or PD-L1 positive Non-small Cell Lung Cancer (NSCLC) in India (Keynote-593) |
| Trial Acronym |
KEYTRUDA® |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| MK3475-593 Version 02 dated 17-May-2018 |
Protocol Number |
| MK3475-593 Version 03 dated 14-Dec-2018 |
Protocol Number |
| MK3475-593 Version 04 dated 03-Jun-2021 |
Protocol Number |
| MK3475-593 Version 05 dated 28 Jun 2022 |
Protocol Number |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
Dr Monisha Sharma |
| Designation |
Director- Clinical Research |
| Affiliation |
MSD Pharmaceuticals Pvt Ltd |
| Address |
6th Floor, Vatika Towers - B, Golf Course Road Sector 54,
Gurgaon
HARYANA
122002
India |
| Phone |
911244647300 |
| Fax |
911244375564 |
| Email |
Monisha.Sharma@merck.com |
|
Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Dr Monisha Sharma |
| Designation |
Director- Clinical Research |
| Affiliation |
MSD Pharmaceuticals Pvt Ltd |
| Address |
6th Floor, Vatika Towers - B, Golf Course Road Sector 54,
Gurgaon
HARYANA
122002
India |
| Phone |
911244647300 |
| Fax |
911244375564 |
| Email |
Monisha.Sharma@merck.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Dr Monisha Sharma |
| Designation |
Director- Clinical Research |
| Affiliation |
MSD Pharmaceuticals Pvt Ltd |
| Address |
6th Floor, Vatika Towers - B, Golf Course Road Sector 54,
Gurgaon
HARYANA
122002
India |
| Phone |
911244647300 |
| Fax |
911244375564 |
| Email |
Monisha.Sharma@merck.com |
|
Source of Monetary or Material Support
Modification(s)
|
| Merck Sharp Dohme LLC a subsidiary of Merck and Co Inc
126 East Lincoln Ave. P.O. Box 2000 Rahway, NJ 07065 |
|
Primary Sponsor
Modification(s)
|
| Name |
Merck Sharp Dohme LLC a subsidiary of Merck and Co Inc |
| Address |
126 East Lincoln Ave.
P.O. Box 2000
Rahway, NJ 07065 |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 8 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Sameer Rastogi |
All India Institute of Medical Sciences |
Room No. 216, 2nd Floor, Dr. B.R.A Institute-Rotary Cancer Hospital; AIIMS, Ansari Nagar, New Delhi - 110029
South
DELHI |
919958975343
samdoc_mamc@yahoo.com |
| Dr Hari Goyal |
Artemis Hospitals |
Room Number 1919; Basement; Sector 51, Gurgaon, Haryana-122001, India
Gurgaon
HARYANA |
911244511111
911246767708
drgoyalhari@hotmail.com |
| Dr Chetan Deshmukh |
Deenanath Mangeshkar Hospital & Research Center |
Department of Oncology, Near Mhatre Bridge, Erandawne, Pune, Maharashtra 411004, India
Pune
MAHARASHTRA |
919850811449
drchetandeshmukh@gmail.com |
| Dr P K Das |
Indraprastha Apollo Hospitals |
Hostel Complex, Basement Annexe, Sarita Vihar, Mathura Road, New Delhi- 1100076, India
New Delhi
DELHI |
911129871683
911141677024
drpratapdas@gmail.com |
| Dr Imran Nisar Shaikh |
Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute |
2nd Floor, Medical Research Department, Rao Saheb Achutrao Patwardhan Marg, Four Bunglows, Andheri West, Mumbai-400053
Mumbai
MAHARASHTRA |
919699947210
912230972030
imran.shaikh@kokilabenhospitals.com |
| Dr Sadashivudu Gundeti |
Nizams Institute of Medical Sciences |
Dept. of Medical Oncology, Punjagutta, Hyderabad, Telangana 500082, India
Hyderabad
TELANGANA |
914023396552
drssgundeti@yahoo.com |
| Dr DCDoval |
Rajiv Gandhi Cancer Institute and Research Centre |
Dept. of Medical Oncology,
Sector-5, Rohini Delhi-110085
New Delhi
DELHI |
91114702441
911127051037
dcdoval@gmail.com |
| DrJyoti Bajpai |
Tata Memorial Hospital |
Room No. 1115, 11th Floor, Homi Bhabha Block, Dr. Ernest Borges Marg, Parel (E),
Mumbai 400 012, Maharashtra, India
Mumbai
MAHARASHTRA |
912224177287
912224177201
drjyotibajpai25@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 8 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee_AIIMS |
Approved |
| Institutional Ethics Committee_Artemis Health Institute |
Approved |
| Institutional Ethics Committee_Deenanath Mangeshkar Hospital & Research Center |
Approved |
| Institutional Ethics Committee_Indraprastha Apollo Hospitals |
Approved |
| Institutional Ethics Committee_Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute |
Approved |
| Institutional Ethics Committee_Tata Memorial Centre |
Approved |
| Institutional Review Board_Rajiv Gandhi Cancer Institute and Research Centre |
Approved |
| NIMS Institutional Ethics Committee_Nizam Institute of medical Sciences |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C439||Malignant melanoma of skin, unspecified, (2) ICD-10 Condition: C349||Malignant neoplasm of unspecifiedpart of bronchus or lung, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Not Applicable |
Not Applicable |
| Intervention |
Pembrolizumab |
Administered as an intravenous (IV) infusion every 3 weeks (Q3W)
Other Names:
KEYTRUDA®
MK-3475 |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
Melanoma Participant:
Has a histologically confirmed diagnosis of unresectable Stage III or metastatic melanoma (Stage IV) not amenable to local therapy
Has received no more than 1 line of prior systemic therapy for unresectable Stage III or Stage IV melanoma including mitogen activated protein kinase inhibitors
Has a Lactate Dehydrogenase (LDH) ≤1.5 times ULN
NSCLC Participant-First Line Treatment:
Has a histologically or cytologically confirmed diagnosis of Stage IV NSCLC
Has a tumor that demonstrate PD-L1 strong expression (PD-L1 ≥50%)
Do not have an EGFR sensitizing mutation AND are anaplastic lymphoma kinase (ALK) translocation negative
Has received no systemic anti-cancer therapy for their metastatic NSCLC
NSCLC Participant-Second Line Treatment and Beyond:
Has a histologically or cytologically confirmed diagnosis of stage IIIB/IV or recurrent NSCLC
Has a tumor that expresses programmed cell death ligand 1 (PD-L1) ≥1%
Has received prior treatment with at least two cycles of a platinum-containing doublet for Stage IIIB/IV or recurrent disease
Has received an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (either erlotinib, gefitinib, or afatinib) if they have an EGFR sensitizing mutation
Has received crizotinib if they have an ALK translocation
NSCLC participants must also meet the following requirements:
Have a life expectancy of at ≥3 months
Provide a formalin fixed tumor tissue sample for PD-L1 biomarker analysis from a recent biopsy of a tumor lesion not previously irradiated; For first line, biopsies obtained PRIOR to the administration of any systemic therapy administered for the treatment of a tumor (such as neoadjuvant/adjuvant/definitive therapy) will not be permitted for analysis. For second line treatment and beyond, no systemic antineoplastic therapy may be administered between the PD-L1 biopsy and initiating study medication
Have documented evidence of the EGFR mutation status or ALK translocation status. If unable to provide documentation of these molecular changes, formalin-fixed paraffin-embedded tumor tissue of any age should be submitted for testing
Have measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the local site investigator/radiologist
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Women of childbearing potential (WOCP) must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of trial treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
WOCP must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of trial treatment
Men of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy |
|
| ExclusionCriteria |
| Details |
For NSCLC Participant only: Has a tumor specimen that is not evaluable for PD-L1 expression by the central laboratory
Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment
Has received prior therapy with an anti- programmed cell death 1 (PD-1), anti-PD-L1, or anti- programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another T-cell receptor (i.e., cytotoxic T-lymphocyte antigen-4 [CTLA-4], OX-40, CD137) or has previously participated in a clinical trial for pembrolizumab (MK-3475)
Has received prior anti-cancer therapy including investigational agent or device within 4 weeks, or completed palliative radiotherapy within 7 days, prior to enrollment
Has recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline
Has recovered adequately from the toxicity and/or complications from major surgery prior to starting trial treatment
Is expected to require any other form of antineoplastic therapy while participating in the trial
Is on systemic corticosteroid therapy within 7 days before the planned date for first dose of treatment or any other form of immunosuppressive medication
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (exceeding 10 mg daily dose of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of trial treatment
Has an active autoimmune disease that has required systemic treatment in the past 2 years
Has a known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., cervical cancer in situ, breast carcinoma) that have undergone potentially curative therapy
Has had an allogeneic tissue/solid organ transplant
Has a history of or current radiographically detectable central nervous system metastases and/or carcinomatous meningitis
Has a severe hypersensitivity (≥ Grade 3) to any excipients in pembrolizumab
Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
Has an active infection requiring systemic therapy including known history of active tuberculosis (Bacillus tuberculosis)
Has a known history of human immunodeficiency virus (HIV) infection
Has a known history of or is positive for hepatitis B (hepatitis B surface antigen [HbsAg] reactive) or hepatitis C (HCV) ribonucleic acid (RNA) [qualitative] is detected
Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
If participant received prior radiation therapy to a symptomatic metastatic lesion, has recovered to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 1 or Grade 0 AEs due to radiation therapy
Is a regular user of any illicit drug or has a recent history (within the last 3 months) of substance abuse including alcohol
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment
Has received a live vaccine within 30 days before the first dose of trial treatment
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator |
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To evaluate the safety of pembrolizumab in Indian patients by measuring the incidence of Adverse Events. |
From time of signing the informed consent form until the end of follow-up. |
|
|
Secondary Outcome
|
|
|
Target Sample Size
|
Total Sample Size="150"
Sample Size from India="150"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 4 |
Date of First Enrollment (India)
Modification(s)
|
31/01/2019 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="7"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
|
Publication Details
|
None Yet |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
Pembrolizumab is approved by the Health Authorities of India for the treatment of advanced lung cancer and melanoma either as first line therapy or after prior therapy. As a condition of granting approval, the Health Authorities of India have required that a Phase 4 clinical trial with Indian participants must be conducted so that adverse reactions related to the drug can reported to the Health Authorities in India. The present study is a Phase 4 safety study of Pembrolizumab to be conducted in India to comply with this condition. This study will provide information on the safety profile of Pembrolizumab for the treatment of NSCLC or Melanoma. This study will record the adverse events that occur during up to two years of treatment with Pembrolizumab in participants with advanced lung cancer or melanoma in India. |