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

NCT06557889 | Recruiting Phase 2

• 1 other identifier: 24VADS04
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 14

Brief Summary

This is a phase II, prospective, non-randomized, single-arm, multicentric study to evaluate the activity and safety of treatment with 4 cycles (instead of 6) of chemotherapy (platinum (cisplatin or carboplatin) and 5-Fluorouracil) in combination with pembrolizumab for the first-line treatment of CPS PD-L1 positive recurrent or metastatic head and neck squamous cell carcinoma. A total of 86 patients will have to be enrolled in this study.

Conditions

Squamous Cell Carcinoma of Head and Neck

Keywords

Squamous Cell Carcinoma of Head and Neck; Pembrolizumab; Cisplatin; Carboplatin; 5-fluorouracil

Outcome Measures

Primary Outcomes (2)

• The endpoint for the activity is defined by the objective response (i.e. complete or partial response) according to the RECIST v1.1 criteria, assessed by the investigator.

  The objective response rate is defined as the ratio of the number of patients with an objective response to the total number of patients.

  48 months for each patient

• The endpoint for the safety is defined as the rate of patients with AE leading to all treatment discontinuation.

  This rate is defined as the ratio of the number of patients with AE leading to all treatment discontinuation to the total number of patients.

  24 months for each patient

Secondary Outcomes (5)

• The objective response rate at 6 months is defined by the presence of an objective response (i.e. complete or partial response) at 6 months according to the RECIST v1.1 criteria, assessed by the investigator.

  6 months for each patient

• Progression-free survival is defined by the time between the date of inclusion and the date on which a first tumor confirmed progression is documented (according to RECIST v1.1 criteria, (Eisenhauer, 2009)) or death from any causes.

  48 months for each patient

• Overall survival is defined by the time between the date of inclusion and the date of death from any cause or the date of the last news (Censored Data).

  48 months for each patient

• Duration of response is defined in the population of patients with an objective response.

  48 months for each patient

• Safety will be assessed according to the toxicity grading of NCI CTCAE v 5.0.

  48 months for each patient

Study Arms (1)

Patient with PD-L1-positive recurrent or metastatic squamous cell carcinoma of the head and neck

EXPERIMENTAL

Drug: Pembrolizumab + Cisplatin/Carboplatin + 5-FU

Interventions

Pembrolizumab + Cisplatin/Carboplatin + 5-FU DRUG

* 4 cycles of combination treatment: 4 cycles of pembrolizumab (200 mg IV on Day 1 of each 3-week cycle) in combination with chemotherapy with platinum salts (cisplatin (100 mg/m2 IV on Day 1 of each 3-week cycle) or carboplatin (AUC 5 IV on Day 1 of each 3-week cycle), at the investigator's choice) and 5-FU (1000 mg/m2/day IV continuous from Day 1-4 of each 3-week cycle). * Maintenance phase: pembrolizumab is continued as monotherapy for up to 24 months of treatment in total (from the first injection of cycle 1).

Patient with PD-L1-positive recurrent or metastatic squamous cell carcinoma of the head and neck

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old on the day of signing the informed consent.
• 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 (or on MRI of the neck if it provides a better measurement of the primary tumor according to standard practice and the investigator judgement) 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. Note : In case of neck MRI assessment, the chest, abdominal, and pelvic CT scan must be performed in addition to assess potential metastases.
• Have a performance status of 0 or 1 on the ECOG performance scale.
• Demonstrate adequate organ function as defined in the protocol.
• 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 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.
• Note: Abstinence is acceptable if it is the subject's usual lifestyle and preferred method of contraception.
• 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.

You may not qualify if:

• Has a disease accessible to local treatment with curative intent.
• 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 complete DPD enzyme deficiency, suggested by an uracilemia \> or equal to 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 this trial (carboplatin, cisplatin, 5-fluorouracil, and pembrolizumab).
• 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 the protocol) 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.
• 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.
• Note: The 5 year period does not apply to the cancer for which the subject is enrolled in the trial.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Active autoimmune disease that has required systemic treatment within the past 2 years (i.e. with the use of corticosteroids or immunosuppressive drugs). Replacement therapy (for example: thyroxine, insulin or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has undergone solid tissue/organ allograft or hematopoietic allograft.
• Has a history of or has non-infectious pneumonia requiring corticosteroids.

Sponsors & Collaborators

• Institut Claudius Regaud: lead

Study Sites (14)

CHU Amiens

Amiens, France

RECRUITING

Institut Sainte Catherine

Avignon, France

NOT YET RECRUITING

Chu Bordeaux - Hopital Saint André

Bordeaux, France

RECRUITING

Centre Jean Perrin

Clermont-Ferrand, France

NOT YET RECRUITING

Centre Oscar Lambret

Lille, France

NOT YET RECRUITING

Chu Limoges

Limoges, France

RECRUITING

Centre Hospitalier Regional de Marseille

Marseille, France

RECRUITING

CHU de Nantes

Nantes, France

NOT YET RECRUITING

Centre Antoine Lacassagne

Nice, France

RECRUITING

Chu de Nimes

Nîmes, France

RECRUITING

CHU Poitiers

Poitiers, France

RECRUITING

Centre Eugène Marquis

Rennes, France

NOT YET RECRUITING

Clinique Pasteur

Toulouse, France

RECRUITING

IUCT-O

Toulouse, France

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab; Cisplatin; Carboplatin; Fluorouracil

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2024
• First Posted: August 16, 2024
• Study Start: October 21, 2024
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: February 11, 2026

Record last verified: 2026-02

Locations

FR (14)