The primary objective of this study is to demonstrate equivalence of pharmacokinetic properties, and comparability of safety and immunogenicity parameters of RPH-030 and Vectibix® following a single (first) intravenous administration to patients with mCRC with wild-type RAS genes as 1-line therapy in combination with FOLFIRI. The additional objective is to perform a pilot evaluation of the efficacy of RPH-030 and Vectibix® following a single (first) intravenous administration to patients with mCRC with wild-type RAS genes as 1-line therapy in combination with FOLFIRI.
This study is a multicenter, double-blind, randomized, comparative, phase I study Treatment with panitumumab in combination with FOLFIRI (de Gramont) within of this study will continue for up to 2 years or disease progression/unacceptable toxicity/patient refusal to continue therapy (in whichever comes first) The study will include the following periods: 1. Screening period: days -27 to 0 (up to 1 administration of the study therapy) If a tumor biopsy is required for histological diagnosis verification and testing of KRAS/NRAS, BRAF mutation status, Her2/neu status, and MSI status, the screening period may be extended up to 42 days 2. Main period: days 1 to 182 Eligible patients will be randomized at the ratio of 1:1 to one of the two study arms: RPH-030 and Vectibix®. During the Main Period of the study, patients will receive panitumumab (RPH-030 or Vectibix®) at a dose of 6 mg/kg intravenously (IV) once every 2 weeks (2 weeks = 1 cycle) in combination with FOLFIRI (after 8 cycles, patients will be switched to the de Gramont regimen) Therapy during the Main Study Period will continue until the earliest of the following: * Completion of 6 months (up to 13 cycles inclusive) * Disease progression (according to RECIST 1.1 criteria or clinical progression) * Development of unacceptable toxicity * Patient's withdrawal of consent to continue treatment Tumor response assessment during the Main Study Period will be performed approximately every 6 weeks Patients will be hospitalized at least twice: at Visit 1 (Day 1) and Visit 3 (Day 29) either before drug administration or on the eve of it; the duration of hospitalization will be at least 24 hours from the start of panitumumab infusion 3. Period of continued therapy: days 183 to 365 During the period of continued therapy, all patients will receive RPH-030 therapy, including those patients who received Vectibix® therapy during the Main Period Therapy during this period will continue until the earliest of the following: * Up to 1 year of therapy * Disease progression (according to RECIST 1.1 criteria or clinical progression) * Development of unacceptable toxicity * Patient's withdrawal of consent to continue treatment Assessment of the tumor response to therapy during the period of continued therapy will be performed approximately once every 8 weeks 4. Treatment Extension Period: days 366 to 729 Participants in the Treatment Extension Period will be patients who demonstrate stable disease (SD) or tumor response after 1 year of therapy. The decision to enter this period will be made by the investigator Therapy during the Treatment Extension Period will continue until the earliest of the following: * For a total duration of up to 2 years * Disease progression (according to RECIST 1.1 criteria or clinical progression) * Development of unacceptable toxicity * Patient's withdrawal of consent to continue treatment 5. Follow-up period (follow-up/FU) For patients who complete the Treatment Extension Period (either as scheduled or prematurely), a Follow-up visit will be scheduled 28 ± 3 days after the last dose of panitumumab. Following this visit, the patient's participation in the study will be considered complete Follow-up (FU) visits will be conducted every 8 weeks (±7 days) until Day 365, death, or withdrawal of consent (whichever occurs first): * For patients who discontinue study therapy due to disease progression or start a new line of treatment (including surgery), FU will be conducted via telephone contact with the patient or relatives to collect overall survival data * For patients who discontinue study therapy for reasons other than progression and have not started new treatment, FU will include CT/MRI assessments until disease progression, initiation of new therapy, or Day 365. Once progression occurs or new therapy starts, these patients will switch to telephone survival follow-up
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
180
RPH-030: concentrate for solution for infusion, 20 mg/mL Panitumumab is diluted in 0.9% sodium chloride for injection under aseptic conditions. The volume required to achieve a dose of 6 mg/kg is withdrawn from the vial and added to a total volume of 100 mL. The final concentration must not exceed 10 mg/mL
Vectibix®: concentrate for solution for infusion, 20 mg/mL Panitumumab is diluted in 0.9% sodium chloride for injection under aseptic conditions. The volume required to achieve a dose of 6 mg/kg is withdrawn from the vial and added to a total volume of 100 mL. The final concentration must not exceed 10 mg/mL
Irinotecan: concentrate for solution for infusion, 20 mg/mL The required amount of Irinotecan should be diluted in either 5% dextrose solution or 0.9% sodium chloride solution for injection
Calcium Folinate: solution for intravenous and intramuscular administration, 10 mg/mL
Fluorouracil: solution for intravascular administration, 50 mg/mL The required amount of Fluorouracil should be diluted in either 5% dextrose solution or 0.9% sodium chloride solution for injection
State Budgetary Healthcare Institution of the Arkhangelsk Region "Arkhangelsk Oncology Dispensary"
Arkhangelsk, Russia
RECRUITINGMoscow City Oncology Hospital No. 62 (MGOB 62)
Istra, Russia
RECRUITINGRegional Budgetary Healthcare Institution "Ivanovo Regional Oncology Dispensary"
Ivanovo, Russia
RECRUITINGState Budgetary Healthcare Institution of Kaluga Region "Kaluga Regional Clinical Oncology Dispensary"
Kaluga, Russia
Area under the pharmacokinetic curve "concentration-time" (AUC(0-336)) of panitumumab
Area under the pharmacokinetic curve "concentration-time" of panitumumab after the first (single dose) administration, truncated at the point before the second administration, i.e. up to 336 hours
Time frame: Pre-dose on Day 1 (first administration) and 1, 3, 6, 8, 12 h post-dose; 24 (Day 2), 72 (Day 4), 96 (Day 5), 120 (Day 6), 192 (Day 9), 264 (Day 12), 336 (Day 15) h post-dose
Area under the pharmacokinetic curve "concentration-time" of panitumumab at steady state (AUC tau ss)
Area under the pharmacokinetic curve "concentration-time" of panitumumab at steady state (after the third administration) (AUC tau ss)
Time frame: Pre-dose on Day 29 (third administration), and 1, 3, 6, 8, 12 h post-dose; 24 (Day 30), 72 (Day 32), 120 (Day 34), 192 (Day 37), 264 (Day 40), 336 (Day 43) h post-dose
Maximum serum concentration of panitumumab after the first administration (Cmax)
Maximum serum concentration of panitumumab after the first administration (Cmax)
Time frame: Pre-dose on Day 1 (first administration) and 1, 3, 6, 8, 12 h post-dose; 24 (Day 2), 72 (Day 4), 96 (Day 5), 120 (Day 6), 192 (Day 9), 264 (Day 12), 336 (Day 15) h post-dose
Maximum serum concentration of panitumumab at steady state (Cmax ss)
Maximum serum concentration of panitumumab at steady state (after the third administration) (Cmax ss)
Time frame: Pre-dose on Day 29 (third administration), and 1, 3, 6, 8, 12 h post-dose; 24 (Day 30), 72 (Day 32), 120 (Day 34), 192 (Day 37), 264 (Day 40), 336 (Day 43) h post-dose
Minimum serum concentration of panitumumab at steady state (Cmin ss)
Minimum serum concentration of panitumumab at steady state (in three administrations) (Cmin ss)
Time frame: Pre-dose on Day 29 (third administration), and 1, 3, 6, 8, 12 h post-dose; 24 (Day 30), 72 (Day 32), 120 (Day 34), 192 (Day 37), 264 (Day 40), 336 (Day 43) h post-dose
Residual concentration of panitumumab at steady state (Ctrough)
Residual concentration of panitumumab at steady state (before the third administration) (Ctrough)
Time frame: Pre-dose on Day 29 (third administration), and 1, 3, 6, 8, 12 h post-dose; 24 (Day 30), 72 (Day 32), 120 (Day 34), 192 (Day 37), 264 (Day 40), 336 (Day 43) h post-dose
Proportion of patients (%) with adverse drug reactions (ADRs) of any severity
Proportion of patients (%) with adverse drug reactions (ADRs) of any severity
Time frame: Up to day 729
Proportion of patients (%) with adverse events (AEs) of any severity
Proportion of patients (%) with adverse events (AEs) of any severity
Time frame: Up to day 729
Proportion of patients (%) with AEs of severity grade ≥ 3
Proportion of patients (%) with AEs of severity grade ≥ 3 according to CTCAE 5.0
Time frame: Up to day 729
Proportion of patients (%) with ADRs of severity grade ≥ 3
Proportion of patients (%) with ADRs of severity grade ≥ 3 according to CTCAE 5.0
Time frame: Up to day 729
Proportion of patients (%) with serious adverse events (SAEs)
Proportion of patients (%) with serious adverse events (SAEs)
Time frame: Up to day 729
Proportion of patients (%) with serious adverse drug reactions (SADRs)
Proportion of patients (%) with serious adverse drug reactions (SADRs)
Time frame: Up to day 729
Proportion of patients (%) who required discontinuation of treatment due to development of ADRs
Proportion of patients (%) who required discontinuation of treatment due to development of ADRs
Time frame: Up to day 729
Proportion of patients (%) who developed anti-drug antibodies (ADA) to panitumumab
Proportion of patients (%) who developed anti-drug antibodies (ADA) to panitumumab
Time frame: Pre-dose on Day 1 (first administration); 1008 (Day 43), 2688 (Day 113), 4032 (Day 169), 5376 (Day 225), 6720 (Day 281), 8400 (Day 351) h post-dose
Proportion of patients (%) who developed neutralizing antibodies (NAb) to panitumumab
Proportion of patients (%) who developed neutralizing antibodies (NAb) to panitumumab
Time frame: Pre-dose on Day 1 (first administration); 1008 (Day 43), 2688 (Day 113), 4032 (Day 169), 5376 (Day 225), 6720 (Day 281), 8400 (Day 351) h post-dose
Proportion of patients (%) developing dermatologic toxicity
Proportion of patients (%) developing dermatologic toxicity
Time frame: Up to day 729
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State Autonomous Healthcare Institution "Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of Tatarstan named after Professor M.Z. Sigal"
Kazan', Russia
RECRUITINGState Budgetary Healthcare Institution "Kuzbass Clinical Oncology Dispensary named after M.S. Rappoport" (SBHI "KCOD")
Kemerovo, Russia
RECRUITINGState Budgetary Healthcare Organisation "Clinical Oncology Dispensary No. 1" under the Ministry of Healthcare of Krasnodar region
Krasnodar, Russia
RECRUITINGRegional Budgetary Healthcare Institution "Kursk Oncology Research and Clinical Center named after G.E. Ostroverkhov"
Kursk, Russia
RECRUITINGState Budgetary Healthcare Institution "Leningrad Regional Clinical Hospital"
Kuz'molovskiy, Russia
RECRUITINGThe Loginov Moscow Clinical Scientific Center (MCSC)
Moscow, Russia
RECRUITING...and 16 more locations