Reduction in the number of chemotherapy cycles in combination with Pembrolizumab in first-line treatment of PD-L1-positive recurrent or metastatic head and neck squamous cell carcinomas

Phase 1

• Conditions: First-line treatment of PD-L1-positive recurrent or metastatic head and neck squamous cell carcinomas; MedDRA version: 27.0Level: LLTClassification code: 10090001Term: Squamous cell carcinoma of head and neck recurrent Class: 100000004864; MedDRA version: 27.0Level: LLTClassification code: 10082179Term: Squamous cell carcinoma of head and neck metastatic Class: 10029104; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2024-514875-16-00
• Lead Sponsor: Oncopole Claudius Regaud

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-05-29
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 93

Inclusion Criteria

Age = 18 years old on the day of signing the informed consent., Have HPV status test results for oropharyngeal cancers defined as a p16 immunohistochemical (IHC) test (determined according to local practices in each center). Note: Cancers of the oral cavity, hypopharynx, and larynx are not required to perform HPV testing by p16 IHC because, by convention, these tumor locations are assumed to be HPV negative., Female subjects of childbearing potential must have a negative pregnancy test within 72 hours prior to receiving the first dose of study treatment., Female subjects of childbearing potential must be willing to follow at least one method of contraception or be surgically sterile, or abstain from heterosexual activity for the duration of the study and until until 4 months for pembrolizumab, 6 months for carboplatin and 5-fluorouracil, and 7,5 months for cisplatin after the last dose of study treatment respectively for each molecule. Subjects of childbearing potential are those who have not been surgically sterilized and who had menstruation in the last 12 months., Male subjects must agree to use at least one method of contraception for the duration of the study and until 180 days after the last dose of study treatment. Note: Abstinence is acceptable if it is the subject's usual lifestyle and preferred method of contraception., Signed written informed consent., Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol., Patient affiliated to a Social Health Insurance in France., Diagnosis of histologically proven recurrent or metastatic squamous cell carcinoma of the head and neck not accessible to treatment with curative intent., Patients must not have received previous systemic therapy administered in the context of recurrent or metastatic disease., If the patient received chemotherapy with a platinum salt as part of multimodal treatment for locally advanced disease, it must have ended at least 6 months before signing the consent., Eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx and larynx. Subjects cannot have a primary tumor site (any histology) in the nasopharynx, sinuses, nasal cavity, salivary glands, or skin, Documented Combined Positive Score (CPS) PD-L1 = 1 (determined according to local practices in each center) Note: the CPS score can be performed on a new biopsy or on an archived tumor specimen, without date limitation., Have measurable disease on CT-scan according to RECIST 1.1 as determined by the investigator. Tumor lesions located in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions., Have a performance status of 0 or 1 on the ECOG performance scale., Demonstrate adequate organ function as defined in Table 1 (see lower). Table 1: Hemoglobin= 9 g/dL (without red blood cell transfusion in the last 7 days) Platelets= 100 x109 /L (without platelet transfusion in the last 7 days) Polynuclear neutrophils= 1,5 x109 /L Glomerular filtration rate (according to MDRD or CKD-EPI)= 60 mL/min Total bilirubin= 1,5 x ULN NB: if = 1.5 x ULN, the patient can enter the study if direct (conjugated) bilirubin is = 1.5 x ULN TGO (ASAT) and TGP (ALAT)= 2.5 x ULN in the absence of liver metastasis Or = 5 x ULN in the presence of liver metastasis Prothrombin level (PT)= 50% unless the subject is receiving anticoagulant therapy, as long as the PT is within

Exclusion Criteria

Has a disease accessible to local treatment with curative intent., Is pregnant or breastfeeding, or expects to conceive or father children during the planned duration of the trial, beginning the screening visit through and until 4 months for pembrolizumab, 6 months for carboplatin and 5-fluorouracil, and 7,5 months for cisplatin after the last dose of study treatment respectively for each molecule., Has previously received treatment with an anti-PD-1 or anti-PD-L1 agent for the treatment of the cancer for which the patient is included in the trial, whether as part of the primary treatment or as part of the relapse., Has a progressive disease within six months following the end of primary treatment with curative intent, if this treatment included systemic treatment with platinum salt., Has a known history of human immunodeficiency virus (HIV) infection., Has known active hepatitis B or C., Received a live vaccine within 30 days before the planned start of study treatment., Has a known history of hypersensitivity to fluorouracil, carboplatin, cisplatin or pembrolizumab or to any of their excipients, according to the SmPCs of these products., For patient receiving the treatment with 5-fluorouracil: has clinically significant active heart disease or myocardial infarction within 6 months; has received a recent or has a concomitant treatment with brivudine (4 weeks before or after 5-FU)., Has a complete DPD enzyme deficiency, suggested by an uracilemia = 150 ng/mL., Has a contraindication to full dose use of a platinum salt, 5-Fluorouracil, or pembrolizumab, in the opinion of the investigator (dose reductions in cycle 1 are not authorized, except in the case of adaptation of the 5-FU due to partial DPD deficiency); the investigator must refer to the SmPC of the products used in the trial (5-fluorouracil, carboplatin, cisplatin, and pembrolizumab)., Has a diagnosis of immunodeficiency or is receiving systemic corticosteroid therapy > 10 mg/day of prednisone equivalent or any other form of immunosuppressive therapy within 7 days before the first dose of trial treatment. The use of corticosteroids as premedication for allergic reactions (e.g., IV contrast) or as prophylactic management of adverse events related to protocol-specified chemotherapies is permitted., The patient must not have received antibiotics within 14 days before inclusion in the trial., Received radiotherapy (or other non-systemic therapy) within 2 weeks prior to inclusion., Subject has not fully recovered (i.e. = Grade 1) from adverse events due to previously administered treatment. Note: Subjects with neuropathy = Grade 2, alopecia = Grade 2, or laboratory values not exceeding the limits in Table 1 (See upper) are an exception to this criterion and may be eligible for the study Note: If the subject has undergone major surgery, they must have adequately recovered from the toxicity and/or complications of the procedure before starting treatment., Currently participating in and receiving study treatment, or has participated in a study of an investigational agent, or used an investigational device, within 4 weeks prior to the first dose of treatment. Note: Participation in the follow-up phase of a previous study is permitted (if the patient is no longer receiving treatment in that study)., Has a life expectancy of less than 3 months and/or has a rapidly progressing illness (eg, tumor bleeding, uncontrolled tumor pain) in the opinion of the investigator., For patient receiving the

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The co-primary objectives are to evaluate the activity and safety of a shortened chemotherapy regimen in combination with pembrolizumab for the first-line treatment of PD-L1-positive R/M HNSCC.;Secondary Objective: Evaluate the objective response rate (ORR) at 6 months, Evaluate progression-free survival (PFS), Evaluate overall survival (OS), Evaluate the duration or response (DoR), Evaluate the safety of the treatment;Primary end point(s): The co-primary endpoint for the activity is the objective response rate. It will be presented using number, percentage and one-sided 95% confidence interval (Binomial exact)., The co-primary endpoint for the safety is the rate of patients with AE leading to all treatment discontinuation. It will be presented using number, percentage and one-sided 95% confidence interval (Binomial exact).