Patient with Locally Advanced Or Metastatic Squamous Cell Cancer Of The Skin MedDRA version: 21.1 Level: PT Classification code 10041834 Term: Squamous cell carcinoma of skin System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: IMP1
Product Code: [NA]
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pembrolizumab
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Other descriptive name: Anti-
Sponsors
FONDAZIONE IRCCS "ISTITUTO NAZIONALE DEI TUMORI"
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have histological diagnosis of squamous cell carcinoma of the skin not amenable to surgical treatment and to radiation with curative purposes or with clinical contraindication to surgery and radiation. Hereafter the possible clinical situations matching these criteria. A multidisciplinary evaluation with surgeon, radiation oncologist and medical oncologist is required to be performed: ¿ skin SCC that has recurred in the same location after two or more surgical procedures and curative resection is deemed unlikely; the tumor is not amenable to radiation as it has been already performed or it is not considered effective anticipated substantial morbidity and/or deformity from surgery (e.g., removal of all or part of a facial structure, such as nose, ear, eyelid, eye; or requirement for limb amputation); radiation therapy is similarly not indicated due to anticipated morbidity and/or deformity ¿ anticipated difficulty in obtaining a curative resection or a curative radiation due to the location of the tumor, the size of disease ¿ anticipated difficulty in reconstructing the area that will be surgically removed ¿ significant comorbidities that preclude the feasibility of a radical surgery ¿ contraindication to radiotherapy: a) previous radiation therapy administered to the area of disease b) site of previous burns c) areas of vascular insufficiency d) skin areas which lead to compromised healing or increased risk of late skin necrosis (e.g.: skin of the back overlying the spine; skin overlying the shin and malleoli of the lower leg) e) patients with ataxia telangiectasia or with xeroderma pigmentosus f) other contraindications according to physician’s judgement (to be reported in clinical chart) OR Have metastatic disease 2. Have measurable disease based on RECIST 1.1. 3. 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. 4. Have a performance status of 0 or 1 on the ECOG Performance Scale. 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 33 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
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. Previous treatment with anti-EGFR agent 3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (prednisone equivalent dose > 10 mg per day) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 4. Has a known history of active TB (Bacillus Tuberculosis) 5. Has previously received an organ transplant 6. Has previously received bone marrow transplantation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Increase in cumulative response rate (PR + CR) obtained by single agent or by combination strategy (pembrolizumab alone or with pembrolizumab + EGFR inhibiting agent) in respect to monotherapy with anti-EGFR agent.;Secondary Objective: Compliance to the treatment and safety Disease control (SD + PR + CR) as best response obtained by single agent or by combination -Progression-Free Survival (PFS) and Overall Survival (OS) -Percentage of patients initially not considered for surgery due to difficulty to obtain a curative treatment that undergo surgery after the treatment (pembrolizumab alone or pembrolizumab + anti EGFR agent) - Reversal of acquired resistance to pembrolizumab obtained through the addition of cetuximab (percentage of responding patients after cetuximab adjunct) ;Primary end point(s): Increase in cumulative response rate (PR + CR) obtained by single agent or by combination strategy (pembrolizumab alone or with pembrolizumab + EGFR inhibiting agent) in respect to monotherapy with anti-EGFR agent. We will consider this approach as effective if the cumulative response rate is at least 45%, with an increase of 17% with respect to previous study with cetuximab in the same setting of disease, in which a response rate of 28% was shown.;Timepoint(s) of evaluation of this end point: 15 patients will be first enrolled and the first evaluation will take place as soon as the last patient has completed 3 cycles of treatment with Pembrolizumab +/- anti EGFR agent. Then, if we do not observe at least 5 responses (partial or complete), no additional patient will be enrolled into the study and we will reject the hypothesis. These patients will be nevertheless followed until progression. If at least 5 patients have responded, then we will enroll 28 additional patients. When the last patient will have completed 4 months of treatment, a second analysis of the response rate will be performed. If the total number of responders is at least 16, then the drug | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Compliance to the treatment and safety - Disease control as best response obtained by single agent or by combination - Progression-Free Survival (PFS) and Overall Survival (OS) - Percentage of patients initially not considered for surgery due to difficulty to obtain a curative treatment that undergo surgery after the treatment (pembrolizumab alone or pembrolizumab + anti EGFR agent) - Reversal of acquired resistance to pembrolizumab obtained through the addition of cetuximab (percentage of responding patients);Timepoint(s) of evaluation of this end point: In case of SD or PD revaluation of the disease at 4 weeks. Revaluation after 6 weeks of combined treatment, revaluation at 4 weeks. Secondary endpoints will be evaluated during the treatment period. | — |
Countries
Italy
Contacts
Public ContactS.C. Oncologia Medica 3 - Tumori Te
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Outcome results
None listed