Immunotherapy +/- EGFR Inhibitor In Advanced/Metastatic cSCC: Tackling Primary And Secondary Resistance

NCT03666325 | Unknown Phase 2 DMC

• 1 other identifier: I-Tackle
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 7

Brief Summary

Cutaneous Squamous Cell Cancer (Cscc, 25%) and basal cell carcinoma (BCC; 75%) are the major subtypes of non-melanoma skin cancer. Most cSCC arise in the head and neck region because it is frequently exposed to sunlight and its ensuing UV radiation-induced DNA damage, which is the major etiologic factor. There is an urgent need to identify new therapeutic targets for patients with locally advanced or metastatic squamous Cell Cancer of the skin. Substantial progress has recently been made in the development of immunotherapy for the treatment of cancer. In particular, the treatment with pembrolizumab alone or in conjunction with an anti epidermal growth factor receptor (EGFR) agent may reverse this condition, so performing radical surgery. Finally, the adjunct of an anti EGFR agent as cetuximab could reverse the primary and secondary resistance to pembrolizumab, with a synergistic effect able to counteract pathway redundancy (i.e. the presence of several concurrent pathways which need to be addressed together) and boosting T cell priming. Hence, there is rationale to combine cetuximab with pembrolizumab in order to increase its effectiveness.

Conditions

Skin Neoplasm

Keywords

metastatic squamous cell cancer of the skin; skin neoplasm; locally advanced squamous cell cancer of the skin; immunotherapy; pembrolizumab; cetuximab

Outcome Measures

Primary Outcomes (1)

• Cumulative response rate

  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.

  15 patients will be enrolled. The first evaluation will take place when the last completes three 21-day cycles of Pembrolizumab+/-cetuximab. If we don't observe at least 5 responses (PR/CR), we will stop the recruitment and reject the hypothesis.

Secondary Outcomes (6)

• Compliance and safety

  Treatment emergent adverse events will be measured throughout the study treatment (at each 21-days cycle.).

• Best response

  After first evaluation (after 9 weeks), every restaging will be performed every 6 weeks

• PFS

  through study completion, an average of 4 years. PFS calculated in each patient as the time from the date of treatment start to the date of first progression or death, whichever comes first

• OS

  through study completion, an average of 4 years. OS, calculated for each patient as the time from the date of treatment start to the date of death.

• Proportion of patients undergoing surgery

  Through study completion an average of 4 years

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Pembrolizumab 200 mg, IV infusion on Day 1 of each 3 week cycle. After 3 cycles patient will be evaluated. In case of disease control (SD, PR, CR) the patient will continue to receive pembrolizumab. In case of progression the patient will receive also Cetuximab (250 mg/m2 after loading dose of 400mg/m2 IV infusion every week.

Drug: Pembrolizumab; Drug: Cetuximab

Interventions

Pembrolizumab DRUG

Pembrolizumab at 200 mg every 3 weeks for 9 weeks.

Also known as: Keytruda

Pembrolizumab

Cetuximab DRUG

In case of first progression or no response cetuximab will be added at a weekly dose of 250 mg.

Also known as: Erbitux

Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent/assent for the trial.
• years of age.
• 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.
• Have metastatic disease
• Have measurable disease based on RECIST 1.1.
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Demonstrate adequate hematological, renal and hepatic organ function as defined in the study protocol.
• Women of childbearing potential should have a negative pregnancy within 72 hours prior to receiving the first dose of study medication.
• Women of childbearing potential must be willing to use an adequate method of contraception as outlined in the study protocol4
• Men of childbearing potential must be willing to use an adequate method of contraception as outlined in the study protocol

You may not qualify if:

• Current or past participation 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.
• Previous treatment with anti-EGFR agent
• 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.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to the trials drugs or their excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (≤ Grade 1 or at baseline) from adverse events.
• Has a known additional malignancy that is progressing or requires active treatment.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has active autoimmune disease that has required systemic treatment in the past 2 years.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation, or is not in the best interest of the subject.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (7)

ASST Spedali Civili di Brescia

Brescia, BS, 25123, Italy

Location

Azienda Ospedaliero Universitaria Careggi

Florence, FI, 50134, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, MI, 20133, Italy

Location

Istituto Europeo di Oncologia

Milan, MI, 20141, Italy

Location

Ospedale di Circolo e Fondazione Macchi

Varese, VA, 21100, Italy

Location

Istituto IRCCS AOU S. Martino

Genova, 16132, Italy

Location

Istituto Nazionale Tumori - Fondazione IRCCS "G. Pascale"

Napoli, 80131, Italy

Location

MeSH Terms

Conditions

Skin Neoplasms

Interventions

pembrolizumab; Cetuximab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Paolo Bossi, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paolo Bossi, MD

CONTACT

+390223902150; paolo.bossi@istitutotumori.mi.it

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: July 16, 2018
• First Posted: September 11, 2018
• Study Start: October 1, 2018
• Primary Completion: October 1, 2020
• Study Completion: October 1, 2022
• Last Updated: September 11, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (7)