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IRCT20150303021315N29 IRCT 2022-04-03 CinnaGen company Non-inferiority clinical trial to compare efficacy and safety of Pembrolizumab (CinnaGen Co.) versus Keytruda® in patients with metastatic Non-Small Cell Lung Cancer (NSCLC) A phase III, non-inferiority clinical trial to compare efficacy and safety of Pembrolizumab (produced by CinnaGen Co.) versus Pembrolizumab (Keytruda®, produced by Merck Company) in metastatic Non-Small Cell Lung Cancer (NSCLC) patients 2022-04-12 anticipated 295 Complete https://irct.ir/trial/59260 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment, Other design features: The Primary objective of this study is to verify non-inferiority of Pembrolizumab (produced by CinnaGen Co.) compared with Keytruda® in metastatic Non-Small Cell Lung Cancer (NSCLC) patients, Randomization description: Eligible patients will be assigned to treatment with the use of stratification, permuted block (length of each block is 3 or 6), and R-CRAN software (version 4.0.3) that will be designed to achieve the overall balance between groups; randomization will be stratified according to Histologic type (squamous vs. non-squamous) and percentage of PDL1 expression (<1, [1-49], ≥50). After randomization procedure, a code will be allocated to each patient that will be used as patient identifier throughout the study. The assigned code will be denoted by 4 initials (corresponding to the first two letters of first name, first two letters of surname) and 3 numbers (center code). Moreover, the code described is followed by the study unique identification code consisting of first three letters of the generic name of the investigational product (which is PEM-) and 3 numbers (corresponding to the randomization number), e.g. ABCD001PEM-001. The randomization number will be assigned in a consecutive way, Blinding description: Both products used in the study will be entirely indistinguishable for patients and ‎health care providers since they are identical in shape, size, Material and color. they don't differ in appearance. The compartments of both pembrolizumab drugs are packaged in same pack. such a way that they do not differ in appearance. The contents of the labels are based on EMEA regulation. The brand's medicine and produced medicine in the factory are completely relabeled and packaged in the same way. The blinding codes are listed on the drug label, and each drug is linked to the patient through the specific code. The patient, medical staff, and other staff are not disclosed to the type of medication that being taken.The group of patients and the type of medication they receive are not disclosed to the researchers and are kept in opaque sealed envelopes with the researcher at each center. In addition, the people who review the results and analyze the data are aware of the type of patient grouping. 3 Metastatic Non-Small Cell Lung Cancer (NSCLC) patients. Intervention 1: 1) Squamous:- Pembrolizumab (CinnaGen) 200mg IV, every 3 weeks for maximum 51 weeks - Paclitaxel 200 mg/m2 IV, every 3 weeks for maximum 12 weeks (4 cycles)- Carboplatin AUC=6 mg/mL * min IV, every 3 weeks for maximum 12 weeks (4 cycles)2) Non-squamous:- Pembrolizumab (CinnaGen) 200mg IV, every 3 weeks for maximum 51 weeks - Pemetrexed 500mg/m2 IV, every 3 weeks for maximum 51 weeks- Carboplatin AUC=5 mg/mL * min IV, every 3 weeks for maximum 12 weeks (4 cycles), after infusion of pemetrexed. Intervention 2: 1) Squamous: - Keytruda® (Merck) 200mg IV, every 3 weeks for maximum 51 weeks- Paclitaxel 200 mg/m2 IV, every 3 weeks for maximum 12 weeks (4 cycles)- Carboplatin AUC=6 mg/mL * min IV, every 3 weeks for maximum 12 weeks (4 cycles)2) Non-squamous:- Keytruda® (Merck) 200mg IV, every 3 weeks for maximum 51 weeks- Pemetrexed 500mg/m2 IV, every 3 weeks for maximum 51 weeks- Carboplatin AUC=5 mg/mL * min IV, every 3 weeks for maximum 12 weeks (4 cycles), after infusion of pemetrexed. Undecided - It is not yet known if there will be a plan to make this available Justification or reason for indecision in sharing IPD is There is no plan for this purpose.
public Dr. Nasim Anjidani
No 42. Attar sq, Attar st, Valiasr st, Vanak sq, Tehran, Iran
Tehran Iran (Islamic Republic of) 1994766411 +98 21 4347 3000 anjidani.n@orchidpharmed.com Orchid Pharmed Co. scientific Dr. Nasim Anjidani
No. 12, 70 Alley, Yousef Abad St., Tehran, Iran
Tehran Iran (Islamic Republic of) 1939653515 +98 21 4347 3000 Anjidani.n@Orchidpharmed.com Orchid Pharmed Company Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Aged 18-75 years old at the time of signing informed consent form 2. Have a histologically or cytologically confirmed diagnosis of NSCLC, is stage IV, does not have an EGFR sensitizing (activating) mutation or ALK translocation or ROS1 rearrangement Have measurable disease based on RECIST 1.1 as determined by the site Have a life expectancy of at least 3 months ECOG Performance Status 0 or 1 Have adequate organ and marrow function Subject has no history of prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy Have provided a formalin fixed tumor tissue sample from a biopsy of a tumor lesion either at the time of or after the diagnosis of metastatic disease has been made AND from a site not previously irradiated to assess for PD-L1 status. Fine needle aspirates, Endobronchial Ultrasound (EBUS) or cell blocks are not acceptable. Needle or excisional biopsies, or resected tissue is required. 18 years 75 years Both Has received systemic therapy for the treatment of their stage IV NSCLC. Completion of treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of treatment Is receiving systemic steroid therapy ≤ 3 days prior to the first dose of trial treatment or receiving any other form of immunosuppressive medication • corticosteroid use on study for management of ECIs, as pre-medication for the control chemotherapies, and/or a premedication for IV contrast allergies/reactions is allowed • Subjects who are receiving daily steroid replacement therapy serve as an exception to this rule. Daily prednisone at doses of 5-7.5 mg is an example of replacement therapy. Equivalent hydrocortisone doses are also permitted if administered as a replacement therapy. • The daily oral administration of 8 milligrams of dexamethasone during visits with concurrent chemotherapy is permitted to prevent chemotherapy-induced nausea and vomiting and pemetrexed-induced cutaneous adverse effects. Is expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent for NSCLC, radiation therapy, and/or surgical resection) Major surgery within 3 weeks of the first dose of trial treatment; received thoracic radiation therapy of > 30 Gy within 6 months of the first dose of trial treatment Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on the baseline brain imaging obtained during the screening period OR identified prior to signing the ICF o Subjects with previously treated brain metastases may participate provided they are clinically stable (neurologically asymptomatic) and have no evidence of new or enlarging brain metastasis by imaging at least 2 weeks after treatment of the brain metastases (e.g., surgery, RT) and are off steroids for at least 3 days prior to the first dose of study medication Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Subjects that require inhaled corticosteroids would not be excluded from the study Has had an allogeneic tissue/solid organ transplant Has interstitial lung disease (ILD) OR has had a history of pneumonitis that has required oral or IV steroids Has received or will receive a live vaccine within 30 days prior to the first administration of study medication. Seasonal flu vaccines that do not contain a live virus are permitted Has an active infection Has known Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) Has known Hepatitis B or Hepatitis C Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. Is, at the time of signing informed consent, a regular user (including “recreational use”) of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol) Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial •If of childbearing potential, female subjects must be willing to use adequate methods throughout the study, starting with the screening visit through 120 days after the last dose of study therapy • Male subjects with a female partner of child-bearing potential must agree to use adequate methods throughout the trial starting with the screening visit through 120 days after the last dose of pembrolizumab is received. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner Clinically active diverticulitis, intra-abdominal abscess, GI obstruction or peritoneal carcinomatosis Has a known sensitivity to pembrolizumab or any component of chemotherapy regimen Has pre-existing Grade ≥ 2 peripheral neuropathy Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤ 1.3 g per day, for a 5-day period C34.9 Malignant neoplasm of unspecified part of bronchus or lung Treatment - Drugs Treatment - Drugs 1) Squamous:- Pembrolizumab (CinnaGen) 200mg IV, every 3 weeks for maximum 51 weeks - Paclitaxel 200 mg/m2 IV, every 3 weeks for maximum 12 weeks (4 cycles)- Carboplatin AUC=6 mg/mL * min IV, every 3 weeks for maximum 12 weeks (4 cycles)2) Non-squamous:- Pembrolizumab (CinnaGen) 200mg IV, every 3 weeks for maximum 51 weeks - Pemetrexed 500mg/m2 IV, every 3 weeks for maximum 51 weeks- Carboplatin AUC=5 mg/mL * min IV, every 3 weeks for maximum 12 weeks (4 cycles), after infusion of pemetrexed. 1) Squamous: - Keytruda® (Merck) 200mg IV, every 3 weeks for maximum 51 weeks- Paclitaxel 200 mg/m2 IV, every 3 weeks for maximum 12 weeks (4 cycles)- Carboplatin AUC=6 mg/mL * min IV, every 3 weeks for maximum 12 weeks (4 cycles)2) Non-squamous:- Keytruda® (Merck) 200mg IV, every 3 weeks for maximum 51 weeks- Pemetrexed 500mg/m2 IV, every 3 weeks for maximum 51 weeks- Carboplatin AUC=5 mg/mL * min IV, every 3 weeks for maximum 12 weeks (4 cycles), after infusion of pemetrexed. Progression-Free Survival (PFS) per RECIST 1.1, which is defined as the time from randomization to disease progression or death from any cause. Timepoint: Every 9 weeks and during the study as needed. Method of measurement: Imaging (CT scan). Overall Survival, which is defined as the time from randomization to death from any cause. Timepoint: During the study. Method of measurement: Patient medical record. Objective response rate (ORR) per RECIST 1.1, which is defined the percentage of people in a study or treatment group who have a partial or complete response to the treatment during the study. Timepoint: Every 9 weeks. Method of measurement: Imaging (CT scan). Progression-Free Survival (PFS) per iRECIST, which is defined as the time from randomization to disease progression or death from any cause. Timepoint: Every 9 weeks and during the study as needed. Method of measurement: Imaging (CT scan). Evaluation of pembrolizumab safety. Timepoint: Throughout study and during each visit. Method of measurement: Assessing and recording adverse events and clinically significant laboratory abnormalities. Assessment of anti-drug antibody (ADA) development in patients. Timepoint: Visits1, 2, 4, 8, 16 and the follow-up visit. Method of measurement: Blood sampling for the evaluation of anti-drug antibody serum levels. Objective response rate (ORR) per iRECIST, which is defined the percentage of people in a study or treatment group who have a partial or complete response to the treatment during the study. Timepoint: Every 9 weeks. Method of measurement: Imaging (CT scan). CinnaGen company Approved 2022-03-15 Ethics committee of National Research Institude of Tuberclulosis and lung Disease Beheshti Universi Masih Daneshvari Hospital, Tehran, Iran Tehran Tehran Iran (Islamic Republic of)