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

Last updated: April 30, 2025
Sponsor: Institut Claudius Regaud
Overall Status: Active - Recruiting

Phase

2

Condition

Lung Cancer

Carcinoma

Head And Neck Cancer

Treatment

Pembrolizumab + Cisplatin/Carboplatin + 5-FU

Once the patient is included in the study, he will receive the treatment schema as defined below:

Clinical Study ID

NCT06557889
24VADS04
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Age ≥ 18 years old on the day of signing the informed consent.

  2. Diagnosis of histologically proven recurrent or metastatic squamous cell carcinomaof the head and neck not accessible to treatment with curative intent.

  3. Patients must not have received previous systemic therapy administered in thecontext of recurrent or metastatic disease.

  4. If the patient received chemotherapy with a platinum salt as part of multimodaltreatment for locally advanced disease, it must have ended at least 6 months beforesigning the consent.

  5. Eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx andlarynx. Subjects cannot have a primary tumor site (any histology) in thenasopharynx, sinuses, nasal cavity, salivary glands, or skin.

  6. Documented Combined Positive Score (CPS) PD-L1 ≥ 1 (determined according to localpractices in each center) Note: the CPS score can be performed on a new biopsy or onan archived tumor specimen, without date limitation.

  7. Have measurable disease on CT-scan according to RECIST 1.1 as determined by theinvestigator. Tumor lesions located in a previously irradiated area are consideredmeasurable if progression has been demonstrated in such lesions.

  8. Have a performance status of 0 or 1 on the ECOG performance scale.

  9. Demonstrate adequate organ function as defined in the protocol.

  10. Have HPV status test results for oropharyngeal cancers defined as a p16immunohistochemical (IHC) test (determined according to local practices in eachcenter). Note: Cancers of the oral cavity, hypopharynx, and larynx are not required toperform HPV testing by p16 IHC because, by convention, these tumor locations areassumed to be HPV negative.

  11. Female subjects of childbearing potential must have a negative pregnancy test within 72 hours prior to receiving the first dose of study treatment.

  12. Female subjects of childbearing potential must be willing to follow at least onemethod of contraception or be surgically sterile, or abstain from heterosexualactivity for the duration of the study and until 4 months for pembrolizumab, 6months for carboplatin and 5-fluorouracil, and 7,5 months for cisplatin after thelast dose of study treatment respectively for each molecule. Subjects ofchildbearing potential are those who have not been surgically sterilized and who hadmenstruation in the last 12 months. Note: Abstinence is acceptable if it is the subject's usual lifestyle and preferredmethod of contraception.

  13. Male subjects must agree to use at least one method of contraception for theduration 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 preferredmethod of contraception.

  14. Signed written informed consent

  15. Patient able to participate and willing to give informed consent prior performanceof any study-related procedures and to comply with the study protocol

  16. Patient affiliated to a Social Health Insurance in France

Exclusion

Exclusion Criteria:

  1. Has a disease accessible to local treatment with curative intent.

  2. Has a progressive disease within six months following the end of primary treatmentwith curative intent, if this treatment included systemic treatment with platinumsalt.

  3. Has a complete DPD enzyme deficiency, suggested by an uracilemia > or equal to 150ng/mL.

  4. Has a contraindication to full dose use of a platinum salt, 5-Fluorouracil, orpembrolizumab, in the opinion of the investigator (dose reductions in cycle 1 arenot authorized, except in the case of adaptation of the 5-FU due to partial DPDdeficiency); the investigator must refer to the SmPC of the products used in thistrial (carboplatin, cisplatin, 5-fluorouracil, and pembrolizumab).

  5. The patient must not have received antibiotics within 14 days before inclusion inthe trial.

  6. Received radiotherapy (or other non-systemic therapy) within 2 weeks prior toinclusion.

  7. Subject has not fully recovered (i.e. ≤ Grade 1) from adverse events due topreviously administered treatment. Note: Subjects with neuropathy ≤ Grade 2, alopecia ≤ Grade 2, or laboratory valuesnot exceeding the limits in Table 1 (See the protocol) are an exception to thiscriterion and may be eligible for the study Note: If the subject has undergone majorsurgery, they must have adequately recovered from the toxicity and/or complicationsof the procedure before starting treatment.

  8. Currently participating in and receiving study treatment, or has participated in astudy of an investigational agent, or used an investigational device, within 4 weeksprior to the first dose of treatment. Note: Participation in the follow-up phase of a previous study is permitted (if thepatient is no longer receiving treatment in that study).

  9. 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.

  10. Has a diagnosis of immunodeficiency or is receiving systemic corticosteroid therapy > 10 mg/day of prednisone equivalent or any other form of immunosuppressive therapywithin 7 days before the first dose of trial treatment. The use of corticosteroidsas premedication for allergic reactions (e.g., IV contrast) or as prophylacticmanagement of adverse events related to protocol-specified chemotherapies ispermitted.

  11. Has a diagnosis of a second cancer diagnosed and/or treated within 5 years precedinginclusion, with the exception of: curatively resected basal cell carcinoma of theskin, curatively resected squamous cell carcinoma of the skin, curatively resectedin situ cervical cancer and curatively resected in situ breast cancer. Note: The 5 year period does not apply to the cancer for which the subject isenrolled in the trial.

  12. Has known active central nervous system (CNS) metastases and/or carcinomatousmeningitis. Note: Subjects with previously treated brain metastases may participate providedthey have been stable (without evidence of progression by imaging using the sameimaging modality for each assessment, either MRI or CT) for at least 4 weeks priorto the first dose of trial treatment, and without neurological symptoms, have nosigns of new or progressing brain metastases, and are not using steroids > 10mg/dayof prednisone equivalent for at least 7 days before study inclusion. This exceptiondoes not include carcinomatous meningitis which is excluded regardless of theclinical situation.

  13. Active autoimmune disease that has required systemic treatment within the past 2years (i.e. with the use of corticosteroids or immunosuppressive drugs). Replacementtherapy (for example: thyroxine, insulin or physiological corticosteroid replacementtherapy for adrenal or pituitary insufficiency, etc.) is not considered a form ofsystemic treatment.

  14. Has undergone solid tissue/organ allograft or hematopoietic allograft.

  15. Has a history of or has non-infectious pneumonia requiring corticosteroids.

  16. Has an active infection requiring systemic anti-infectious treatment.

  17. Has a history or current evidence of any condition, therapy, or laboratoryabnormality that could interfere with the results of the trial or with the subject'sparticipation throughout the duration of the trial, or is not in the best interestof the subject to participate, in the opinion of the investigator.

  18. Is pregnant or breastfeeding, or expects to conceive or father children during theplanned duration of the trial, beginning the screening visit through and until 4months for pembrolizumab, 6 months for carboplatin and 5-fluorouracil, and 7,5months for cisplatin after the last dose of study treatment respectively for eachmolecule.

  19. Has previously received treatment with an anti-PD-1 or anti-PD-L1 agent for thetreatment of the cancer for which the patient is included in the trial, whether aspart of the primary treatment or as part of the relapse.

  20. Has a known history of human immunodeficiency virus (HIV) infection.

  21. Has known active hepatitis B or C.

  22. Received a live vaccine within 30 days before the planned start of study treatment.

  23. Has a known history of hypersensitivity to fluorouracil, carboplatin, cisplatin orpembrolizumab or to any of their excipients, according to the SmPCs of theseproducts.

  24. For patient receiving the treatment with 5-fluorouracil: has clinically significantactive heart disease or myocardial infarction within 6 months; has received a recentor has a concomitant treatment with brivudine (4 weeks before or after 5-FU).

  25. For patient receiving the treatment with cisplatin: has a neuropathy caused bycisplatin, has a hearing problem, has a treatment with phenytoin with prophylacticaim.

  26. For patient receiving the treatment with pembrolizumab: has a history ofuncontrolled or symptomatic cardiac disease.

  27. Any psychological, familial, geographic or social situation, according to thejudgment of investigator, potentially preventing the provision of informed consentor compliance to study procedure

  28. Patient who has forfeited his/her freedom by administrative or legal award or who isunder legal protection (curatorship and guardianship, protection of justice)

Study Design

Total Participants: 86
Treatment Group(s): 2
Primary Treatment: Pembrolizumab + Cisplatin/Carboplatin + 5-FU
Phase: 2
Study Start date:
October 21, 2024
Estimated Completion Date:
September 30, 2030

Connect with a study center

  • Chu Bordeaux - Hopital Saint André

    Bordeaux,
    France

    Active - Recruiting

  • Chu Limoges

    Limoges,
    France

    Active - Recruiting

  • Centre Hospitalier Regional de Marseille

    Marseille,
    France

    Active - Recruiting

  • Centre Antoine Lacassagne

    Nice,
    France

    Active - Recruiting

  • Chu de Nimes

    Nimes,
    France

    Active - Recruiting

  • CHU Poitiers

    Poitiers,
    France

    Active - Recruiting

  • Clinique Pasteur

    Toulouse,
    France

    Active - Recruiting

  • IUCT-O

    Toulouse,
    France

    Active - Recruiting

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