Head and Neck Squamous Cell Carcinoma
Conditions
Keywords
Head and Neck Squamous Cell Carcinoma, RPH-002
Brief summary
The primary objective of the study is to evaluate the comparability of efficacy, safety, and immunogenicity of RPH-002 and Erbitux® when administered in combination with docetaxel and cisplatin as first-line therapy in patients with advanced head and neck squamous cell carcinoma
Detailed description
This study is a international, multicenter, open-label, randomized, parallel-group Phase III study The study will include the following periods: 1. Screening Period 1 Includes Days -14 to -1 (prior to the first administration of the investigational product/comparator) 2. Main Period (Period 1) The main study period includes Days 1-126 The Main Period begins with administration of cetuximab (RPH-002 or Erbitux®) and chemotherapy on Day 1 of Cycle 1. Chemotherapy continues for up to 6 cycles, each lasting 3 weeks (21 days). Chemotherapy agents are administered no earlier than 1 hour after completion of cetuximab infusion. Cetuximab is administered weekly for up to 18 doses In Period 1, tumor response is assessed every 6 weeks 3. Screening Period 2 Includes Days -7 to 0 (prior to Visit 1 of the Maintenance Therapy Period) During Screening Period 2, the patient's general condition and laboratory and instrumental test results are evaluated to determine eligibility for continuation of therapy in the Maintenance Therapy Period 4. Maintenance Therapy Period (Period 2) Includes Days 127-386 In the Maintenance Therapy Period, patients with a tumor response or stable disease at Week 18 of Period 1 are included in the study. Tumor response is assessed according to RECIST 1.1 criteria: * Complete Response (CR) - disappearance of all target lesions, confirmed by CT scans for at least 4 weeks; the short axis of any lymph node previously considered pathological (target or non-target) must be \<10 mm * Partial Response (PR) - at least a 30% decrease in the sum of diameters of target lesions, maintained for at least 4 weeks compared with baseline (screening) measurements * Progressive Disease (PD) - at least a 20% increase in the sum of diameters of target lesions compared with the smallest sum recorded during the study (with an absolute increase of at least 5 mm), or the appearance of one or more new lesions * Stable Disease (SD) - neither sufficient shrinkage in the sum of diameters to qualify as partial response nor sufficient increase to qualify as progressive disease compared with the smallest sum recorded during the study During the Maintenance Therapy Period, patients receive monotherapy with cetuximab at 250 mg/m² once weekly. The maximum number of administrations of cetuximab during this period is 36 Therapy continues until the earliest of the following: * up to 54 weeks from the start of study treatment * disease progression (per RECIST 1.1 or clinical progression) * unacceptable toxicity Radiologically confirmed progression according to RECIST 1.1 criteria is defined as an increase of at least 20% in the sum of diameters of target lesions compared with the smallest sum recorded during the study (with an absolute increase of at least 5 mm), or the appearance of one or more new lesions In Period 2, tumor response is assessed every 6 weeks 5. Follow-up Period The Follow-Up Period assesses the safety of study therapy in all patients who complete Period 1 and do not enter Period 2, as well as in patients who complete therapy in Period 2. The period lasts 28 ± 3 days after the last study drug administration (if therapy completes as planned at 54 weeks) or until death, loss to follow-up, or Day 365, whichever occurs first. A single follow-up visit is conducted 28 ± 3 days after the last study drug administration
Interventions
DRUGRPH-002
RPH-002: solution for infusion, 100 mg/20 mL (5 mg/mL) per vial RPH-002 is administered IV once weekly. The first dose is 400 mg/m², given as a 20 mg/m² IV test dose over 10 minutes followed by 380 mg/m² IV over the remainder of 120 minutes. Subsequent weekly doses are 250 mg/m² IV over 60 minutes Thirty to sixty minutes prior to the infusion of RPH-002, premedication with diphenhydramine 50 mg (or other H1-receptor antagonist) administered orally or intravenously and a glucocorticosteroid (e.g., dexamethasone 8 mg) is required
DRUGErbitux®
Erbitux®: solution for infusion, 5 mg/mL; vials of 10, 20, 50, and 100 mL containing 50, 100, 250, and 500 mg of the drug, respectively Erbitux® is administered IV once weekly. The first dose is 400 mg/m², given as a 20 mg/m² IV test dose over 10 minutes followed by 380 mg/m² IV over the remainder of 120 minutes. Subsequent weekly doses are 250 mg/m² IV over 60 minutes Thirty to sixty minutes prior to the infusion of Erbitux®, premedication with diphenhydramine 50 mg (or other H1-receptor antagonist) administered orally or intravenously and a glucocorticosteroid (e.g., dexamethasone 8 mg) is required
DRUGCisplatin
Solution for injection (500 μg / 1 mg / 1 mL; 10 / 25 / 50 / 100 mg per vial) Cisplatin is administered intravenously at 75 mg/m² once every 3 weeks. Hydration is required to promote diuresis and reduce cisplatin-related nephrotoxicity
DRUGDocetaxel
Concentrate for solution for infusion (40 mg/mL; 0.5 mL / 2 mL per vial) Docetaxel is administered intravenously at 75 mg/m² over 60 minutes once every 3 weeks, prior to the cisplatin infusion and concurrently with prehydration
Sponsors
R-Pharm
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Period (Period 1) 1. A voluntarily signed and dated Informed Consent form (ICF) of the patient 2. Histologically confirmed squamous cell carcinoma of the head and neck 3. Documented unresectable locoregional recurrence or distant metastases, or progression after prior chemoradiotherapy or combination therapy completed \>3 months before screening, not amenable to local treatment (except cases with high risk of tumor lysis or bleeding), or newly diagnosed metastatic disease not previously treated with systemic therapy. Study treatment is first-line therapy 4. At least one measurable lesion per RECIST 1.1 5. Karnofsky performance status ≥70% 6. Screening laboratory values within the following limits (per local lab normal ranges): * Hemoglobin ≥90 g/L * Leukocytes ≥3.0 × 10\^9/L * Neutrophils ≥1.5 × 10\^9/L * Platelets ≥100 × 10\^9/L * Total bilirubin ≤2 × Upper Limit of Normal (ULN) * Aspartate aminotransferase (AST) ≤3 × ULN * Alanine aminotransferase (ALT) ≤3 × ULN * Estimated glomerular filtration rate (eGFR) ≥60 mL/min 7. Men and women of childbearing potential, and women within 2 years of menopause, must agree to use reliable contraception from informed consent through at least 6 months after study treatment; women of childbearing potential must have a negative urine pregnancy test. Women with no reproductive potential (≥2 years post-menopause or surgically sterile) are exempt 8. Ability and willingness to comply with study protocol and procedures for the planned duration of participation Maintenance Therapy Period (Period 2) 1. Registered objective response (stable disease or partial/complete response according to RECIST 1.1 criteria) to the therapy administered during the main study period 2. Ability and willingness to provide written informed consent for participation in Period 2 3. Karnofsky performance status ≥ 70% 4. Laboratory values within the following limits (per local lab normal ranges): * Hemoglobin ≥ 90 g/L * Leukocytes ≥ 3.0 × 10\^9/L * Neutrophils ≥ 1.5 × 10\^9/L * Platelets ≥ 100 × 10\^9/L * Total bilirubin ≤ 2 × ULN (upper limit of normal) * AST ≤ 3 × ULN * ALT ≤ 3 × ULN * eGFR ≥ 60 mL/min 5. Men and women of childbearing potential, and women within 2 years of menopause, must agree to use reliable contraception from informed consent through at least 6 months after study treatment; women of childbearing potential must have a negative urine pregnancy test. Women with no reproductive potential (≥2 years post-menopause or surgically sterile) are exempt
Exclusion criteria
Main Period (Period 1) 1. Prior therapy with cetuximab or other monoclonal antibody-based biologics 2. Chemotherapy, radiotherapy, or surgery for head and neck cancer within 3 months before screening 3. Any other surgery (except biopsy, implantable venous port placement, or urgent non-cancer surgery) within 3 months before screening 4. Nasopharyngeal carcinoma 5. Other malignancy within the past 5 years or prior/concurrent squamous cell carcinoma (except cured in situ ductal carcinoma, cervical carcinoma in situ, basal cell or squamous cell skin cancer) 6. Expected survival \< 3 months 7. Women who are pregnant or breastfeeding, or unwilling to use effective contraception during the study and for at least 6 months after 8. Significant cardiovascular disease per investigator, including uncontrolled hypertension (systolic ≥180 mmHg or diastolic ≥130 mmHg), coronary artery disease, myocardial infarction within 12 months, high-risk uncontrolled arrhythmias, or uncontrolled heart failure 9. Active infection requiring systemic antibiotic therapy 10. Ongoing systemic immunotherapy, hormone therapy, or other cancer treatments not specified in the protocol within 6 months prior to screening or during the study 11. Known or suspected brain metastases, including parenchymal, leptomeningeal, or dural involvement associated with symptoms 12. Positive screening for HBsAg, anti-HCV, anti-HIV1/2 antibodies, or syphilis within 3 months prior to screening 13. Conditions preventing compliance with the study protocol per investigator 14. Participation in another investigational drug study within 6 months prior to screening 15. Unstable medical conditions, including uncontrolled diabetes, psychiatric disorders, or uncontrolled seizures, that could interfere with protocol adherence 16. Known hypersensitivity to any component of study therapy or combination chemotherapy drugs 17. Excessive alcohol use (\>10 standard drinks/week) or history of alcoholism or substance abuse associated with symptoms. One standard drink = 250 mL beer, 125 mL wine, or 30 mL spirits Maintenance Therapy Period (Period 2) 1. Absence of a confirmed objective response to the administered therapy during the main study period, defined as failure to achieve disease stabilization or a partial/complete response according to RECIST v1.1 2. Women who are pregnant or breastfeeding, or unwilling to use effective contraception during the study and for at least 6 months after 3. Significant cardiovascular disease per investigator, including uncontrolled hypertension (systolic ≥180 mmHg or diastolic ≥130 mmHg), coronary artery disease, myocardial infarction within 12 months, high-risk uncontrolled arrhythmias, or uncontrolled heart failure 4. Active infection requiring systemic antibiotics 5. Ongoing systemic immunotherapy, hormone therapy, or other cancer treatments not specified in the protocol for Period 2 6. Known or suspected brain metastases, including parenchymal, leptomeningeal, or dural involvement associated with symptoms 7. Conditions preventing compliance with study procedures per investigator 8. Participation in another investigational drug study 9. Unstable medical conditions, including uncontrolled diabetes, psychiatric disorders, or uncontrolled seizures, that could interfere with protocol adherence 10. Excessive alcohol use (\>10 standard drinks/week) or history of alcoholism or substance abuse associated with symptoms. One standard drink = 250 mL beer, 125 mL wine, or 30 mL spirits
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (%) (ORR) | At Visits 6 (Day 36), 12 (Day 78), and 18 (Day 120) | Objective response rate (%) (ORR) for a period of up to 18 weeks of therapy inclusive The objective response rate (ORR) is defined as the percentage of patients in each treatment group who achieve a complete or partial tumor response to therapy according to RECIST 1.1 criteria: * Complete Response (CR) - disappearance of all target lesions, confirmed by CT scans for at least 4 weeks; the short axis of any lymph node previously considered pathological (target or non-target) must be \<10 mm * Partial Response (PR) - at least a 30% decrease in the sum of diameters of target lesions, maintained for at least 4 weeks compared with baseline (screening) measurements |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (%) (DCR; CR + PR + SD) | At Visits 6 (Day 36), 12 (Day 78), and 18 (Day 120) | Disease Control Rate (DCR; CR + PR + SD), %, achieved within up to 18 weeks from the start of study treatment (inclusive) The disease control rate is defined as the percentage of patients in a given treatment group who achieve a complete response, partial response, or stable disease during therapy, in accordance with RECIST 1.1 criteria: * Complete Response (CR) - disappearance of all target lesions, confirmed by CT scans for at least 4 weeks; the short axis of any lymph node previously considered pathological (target or non-target) must be \<10 mm * Partial Response (PR) - at least a 30% decrease in the sum of diameters of target lesions, maintained for at least 4 weeks compared with baseline (screening) measurements * Stable Disease (SD) - neither sufficient shrinkage in the sum of diameters to qualify as partial response nor sufficient increase to qualify as progressive disease compared with the smallest sum recorded during the study |
| Proportion of patients (%) with adverse drug reactions (ADRs) of any severity | Up to Day 365 | Proportion of patients (%) with adverse drug reactions (ADRs) of any severity |
| Proportion of patients (%) with adverse events (AEs) of any severity | Up to Day 365 | Proportion of patients (%) with adverse events (AEs) of any severity |
| Proportion of patients (%) with AEs of severity grade ≥ 3 | Up to Day 365 | Proportion of patients (%) with AEs of severity grade ≥ 3 according to CTCAE 5.0 |
| Proportion of patients (%) with ADRs of severity grade ≥ 3 | Up to Day 365 | Proportion of patients (%) with ADRs of severity grade ≥ 3 according to CTCAE 5.0 |
| Proportion of patients (%) with serious adverse events (SAEs) | Up to Day 365 | Proportion of patients (%) with serious adverse events (SAEs) |
| Proportion of patients (%) with serious adverse drug reactions (SADRs) | Up to Day 365 | Proportion of patients (%) with serious adverse drug reactions (SADRs) |
| Proportion of patients (%) who required discontinuation of treatment due to development of ADRs/SADRs | Up to Day 365 | Proportion of patients (%) who required discontinuation of treatment due to development of ADRs/SADRs |
| Proportion of patients (%) who developed anti-drug antibodies (ADA) to cetuximab | Pre-dose in Period 1 on Days 1, 15, 29, 57, and 85, and 28 ± 3 days post-last infusion; pre-dose in Period 2 on Days 6, 12, 18, 24, 30, and 36 | Proportion of patients (%) who developed anti-drug antibodies (ADA) to cetuximab |
| Proportion of patients (%) who developed neutralizing antibodies (NAb) to cetuximab | Pre-dose in Period 1 on Days 1, 15, 29, 57, and 85, and 28 ± 3 days post-last infusion; pre-dose in Period 2 on Days 6, 12, 18, 24, 30, and 36 | Proportion of patients (%) who developed neutralizing antibodies (NAb) to cetuximab |
Countries
Russia, Uzbekistan
Contacts
STUDY_DIRECTORMikhail Samsonov
R-Pharm
Outcome results
None listed