FLUOROURACIL for Head and neck squamous cell carcinoma (recurrent or metastatic) | PD-L1-positive

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years old on the day of signing the informed consent.\n- 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.\n- Female subjects of childbearing potential must have a negative pregnancy test within 72 hours prior to receiving the first dose of study treatment.\n- 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.\n- 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.\n- Signed written informed consent.\n- Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol.\n- Patient affiliated to a Social Health Insurance in France.\n- Diagnosis of histologically proven recurrent or metastatic squamous cell carcinoma of the head and neck not accessible to treatment with curative intent.\n- Patients must not have received previous systemic therapy administered in the context of recurrent or metastatic disease.\n- 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.\n- 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\n- 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.\n- 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 to assess potential metastases.\n- Have a performance status of 0 or 1 on the ECOG performance scale.\n- Demonstrate adequate organ function as defined in Table 1 (see lower). Table 1: Hemoglobin\t≥ 9 g/dL (without red blood cell transfusion in the last 7 days) Platelets\t≥ 100 x109 /L (without platelet transfusion in the last 7 days) Polynuclear neutrophils\t≥ 1,5 x109 /L Glomerular filtration rate (according to MDRD or CKD-EPI)\t≥ 60 mL/min Total bilirubin\t≤ 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)\t≤ 2.5 x ULN in the absence of liver metastasis Or ≤ 5 x ULN in the presence of liver metastasis Prothrombin level (PT)\t≥ 50% unless the subject is receiving anticoagulant therapy, as long as the PT is within the therapeutic range of intended anticoagulant use. Activated partial thromboplastin time (aPTT)\t≤ 1,5 unless the subject is receiving anticoagulant therapy, as long as the aPTT is within the therapeutic range of intended anticoagulant use. ULN = Upper Limit of Normal"}

Exclusion criteria

• {"criterion_text":"- Has a disease accessible to local treatment with curative intent.\n- 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.\n- 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.\n- 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.\n- Has a known history of human immunodeficiency virus (HIV) infection.\n- Has known active hepatitis B or C.\n- Received a live vaccine within 30 days before the planned start of study treatment.\n- 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.\n- 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).\n- Has a complete DPD enzyme deficiency, suggested by an uracilemia ≥ 150 ng/mL.\n- 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).\n- 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.\n- The patient must not have received antibiotics within 14 days before inclusion in the trial.\n- Received radiotherapy (or other non-systemic therapy) within 2 weeks prior to inclusion.\n- 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.\n- 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).\n- 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.\n- For patient receiving the treatment with cisplatin: has a neuropathy caused by cisplatin, has a hearing problem, has a treatment with phenytoin with prophylactic aim.\n- For patient receiving the treatment with pembrolizumab: has a history of uncontrolled or symptomatic cardiac disease.\n- Any psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the provision of informed consent or compliance to study procedure\n- Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice)\n- Has a diagnosis of a second cancer diagnosed and/or treated within 5 years preceding inclusion, with the exception of: curatively resected basal cell carcinoma of the skin, curatively resected squamous cell carcinoma of the skin, curatively resected in 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 is enrolled in the trial.\n- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Subjects with previously treated brain metastases may participate provided they have been stable (without evidence of progression by imaging using the same imaging modality for each assessment, either MRI or CT) for at least 4 weeks prior to the first dose of trial treatment, and without neurological symptoms, have no signs of new or progressing brain metastases, and are not using steroids > 10mg/day of prednisone equivalent for at least 7 days before study inclusion. This exception does not include carcinomatous meningitis which is excluded regardless of the clinical situation.\n- 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.\n- Has undergone solid tissue/organ allograft or hematopoietic allograft.\n- Has a history of or has non-infectious pneumonia requiring corticosteroids.\n- Has an active infection requiring systemic anti-infectious treatment.\n- Has a history or current evidence of any condition, therapy, or laboratory abnormality that could interfere with the results of the trial or with the subject's participation throughout the duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the investigator."}

Primary endpoints

• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Objective response rate (complete or partial response) assessed by the investigator (RECIST v1.1); presented as number, percentage and one-sided 95% confidence interval (Binomial exact)."}
• {"endpoint_text":"- The co-primary endpoint for the safety is the rate of patients with AE leading to any treatment discontinuation. It will be presented using number, percentage and one-sided 95% confidence interval (Binomial exact).","definition_or_measurement_approach":"Rate of patients with adverse events resulting in discontinuation of any study treatment; presented as number, percentage and one-sided 95% confidence interval (Binomial exact)."}

Secondary endpoints

• {"endpoint_text":"- 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. It is defined by the ratio of the number of patients presenting an objective response at 6 months to the total number of patients.","definition_or_measurement_approach":"ORR at 6 months per RECIST v1.1 assessed by investigator; numerator = patients with objective response at 6 months, denominator = total patients."}
• {"endpoint_text":"- 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. Patients alive and progression free on the date of last news will be censored on the date of last tumor assessment.","definition_or_measurement_approach":"PFS measured from date of inclusion to first documented tumor progression per RECIST v1.1 or death; censoring at last tumor assessment if alive and progression-free."}
• {"endpoint_text":"- 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).","definition_or_measurement_approach":"OS measured from inclusion to death from any cause; censor at last contact if alive."}
• {"endpoint_text":"- Duration of response is defined in the population of patients with an objective response. It is defined by the time between the date of confirmed objective response and the date on which a first confirmed tumor progression is documented (according to RECIST v1.1 criteria, Eisenhauer, 2009) or death from all causes. Patients alive and progression free at last news will be censored on the date of last tumor assessment.","definition_or_measurement_approach":"DoR measured from date of confirmed objective response to first confirmed progression per RECIST v1.1 or death; censor at last tumor assessment if alive and progression-free."}
• {"endpoint_text":"- Safety will be assessed according to the toxicity grading of NCI CTCAE v 5.0.","definition_or_measurement_approach":"Safety reported using NCI CTCAE v5.0 grading for adverse events."}

France

Earliest CTIS Part Ii Submission Date

04-07-2024

Latest Decision Or Authorization Date

02-04-2026

Processing Time Days

637

Number Of Sites

13

Number Of Participants

86

Primary sponsor

Full Name

Oncopole Claudius Regaud

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France