Resectable head and neck mucosal melanoma MedDRA version: 20.0 Level: PT Classification code 10067821 Term: Head and neck cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10053571 Term: Melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Other descriptiv
Sponsors
Gustave Roussy
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Be willing and able to provide written informed consent/assent for the trial. 2. Be >= 18 years of age on day of signing informed consent. 3. Present with a resectable head and neck mucosal melanoma. 4. Be eligible for surgical treatment (without any contraindications). 5. Be eligible for adjuvant radiotherapy. 6. Have measurable disease based on RECIST 1.1. 7. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor. 8. Have a performance status of 0 or 1 on the ECOG Performance Scale. 9. Demonstrate adequate organ function as defined below, all screening labs should be performed within 10 days of treatment initiation: - Hematological Absolute neutrophil count (ANC) =1,500 /mcL Platelets =100,000 / mcL Hemoglobin =9 g/dL or =5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) - Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) =1.5 X upper limit of normal (ULN) OR =60 mL/min for subject with creatinine levels > 1.5 X institutional ULN Creatinine clearance should be calculated per institutional standard. - Hepatic Serum total bilirubin = 1.5 X ULN OR Direct bilirubin = ULN for subjects with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) = 2.5 X ULN OR = 5 X ULN for subjects with liver metastases Albumin >2.5 mg/dL - Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) =1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Activated Partial Thromboplastin Time (aPTT) =1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants 10. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 11. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. 12. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. 13. Patient affiliated to a social security system or beneficiary of the same Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. 2. Has a metastatic disease. 3. Has a non resectable melanoma. 4. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (except topical or inhaled steroids) or any other form of immunosuppressive therapy within 2 weeks prior to the first dose of trial treatment. 5. Has a known history of active TB (Bacillus Tuberculosis) 6. Hypersensitivity to pembrolizumab or any of its excipients. 7. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to D1 of study treatment or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 8. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks or 5 half-life times (whatever the shorter) prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to a previously administered agent. - Note: Subjects with = Grade 2 neuropathy are an exception to this criterion and may qualify for the study. - Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 9. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 10. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 11. Has active autoimmune and/or immune mediated inflammatory disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 12. Has known history of, or any evidence of active, non-infectious pneumonitis. 13. Has an active infection requiring systemic therapy. 14. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 15. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 16. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective will be to estimate the disease free survival (DFS) of patients with resectable head and neck mucosal melanomas treated by neo-adjuvant anti-PD1 followed by surgery, radiotherapy and maintenance immunotherapy in order to compare it to historical DFS results of this kind of patients treated by surgery and radiotherapy;Secondary Objective: - Evaluation of overall survival - Evaluation of loco-regional control - Evaluation of preoperative efficacy of anti-PD1 immunotherapy - Evaluation of the safety of anti-PD1 immunotherapy - Identification of candidate prognostic and predictive biomarkers ;Primary end point(s): Disease free survival, defined as the time between the inclusion in the trial and the date of the first event defined as local, regional, distant relapse or death whatever the cause;Timepoint(s) of evaluation of this end point: The primary end-point will be disease-free survival at 2 years. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall survival (OS) - Locoregional control (Time to locoregional relapse, TTLRC) - Efficacy (Objective response, RECIST 1.1) - Acute toxicity (CTC-NCI V4) - Translational criteria . Ex vivo response to anti-PD1 . Prognostic value of biomarkers including PDL1 expression and mutational load . Variation of circulating lymphocytes (before–after treatment) ;Timepoint(s) of evaluation of this end point: Efficacy will be assessed pre-operatively performing clinical examination with nasofibroscopy and MRI. Tumor samples from surgery will be then analyzed. Translational study - immunological and histological response to anti-PD1 on tumor samples removed by surgery (evaluating before and after treatment the expression of PD-L1 in tumor cells, the number of tumor infiltrating lymphocytes and characterization of their phenotype in frozen or formalin fixed paraffin embedded tumor tissue). - Circulating lymphocyte subpopulations as well as soluble immune factors in blood: before any treatment, after two neo-adjuvant injections of pembrolizumab, after two maintenance injections of pembrolizumab and at the end of treatment. | — |
Countries
France
Contacts
Public ContactCRA
Gustave Roussy
Outcome results
None listed