Neoadjuvant Pembrolizumab in Cutaneous Squamous Cell Carcinoma

ConditionsCutaneous Squamous Cell Carcinoma of the Head and Neck Head and Neck Cancer

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorQueensland Health

About this trial

Cutaneous Squamous Cell Carcinoma (cSCC) is typically associated with a high tumour mutation burden, with the majority caused by Ultraviolet (UV) exposure (Pickering et al., 2014).

The use of this trial using neoadjuvant Pembrolizumab in patients with cSCC who will otherwise undergo highly morbid radical surgical resection has multiple potential advantages, including:

1. Reduction in surgical and radiotherapy morbidity by reducing tumour burden and allowing the appropriate selection of patients to undergo post-operative radiotherapy; 2. Provision of immediate information about pathological response and 3. Access to tissue to provide insight into resistance mechanisms and identification of biomarkers of response.

The Investigators hypothesized that the use of neoadjuvant Pembrolizumab could reduce tumour burden allowing appropriate selection of patients undergoing radical surgical resection and adjuvant radiotherapy.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Histologically confirmed diagnosis of invasive cSCC that is locally advanced (Stage II-IV on AJCC 8th edition) assessed preoperatively as sufficiently high risk that they will warrant post-operatively RT (as recommended by MDT) who is a candidate for a complete resection.

Participants must have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days prior to the start of treatment.

Participants must have adequate organ function

Disqualifiers

Participant has metastatic/unresectable cSCC that cannot be potentially cured with surgical resection, radiotherapy, or with a combination of surgery and radiotherapy.

Participant has any other histologic type of skin cancer other than invasive squamous cell carcinoma as the primary disease under study, eg, basal cell carcinoma that has not been definitively treated with surgery or radiation, Bowen's disease, merkel cell carcinoma, melanoma.

Participants with any prior allogeneic solid organ or hematopoietic stem cell transplantations are excluded.

Participant has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).

Trial design

Design model

Single group

Treatments tested in this trial

Pembrolizumab
Drug
Delivery of neo-adjuvant Pembrolizumab

Treatment groups

27 Participants

are divided into 1 treatment group

Group A: Arm AExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Assess the rate of pathological response to neo-adjuvant Pembrolizumab

To assess the rate of pathological response of neo-adjuvant Pembrolizumab in patients with locally advanced, resectable cSCC. Response will be measured by reviewing tissue samples taken at either surgical resection or biopsy following 4 cycles of neo-adjuvant Pembrolizumab. A pathological complete response will show no viable tumour cells. Pathological response will be determined as: Major Pathological response (less than or equal to 10% viable tumour cells remaining following 4 cycles of Neo-adjuvant Pembrolizumab) Pathological Partial Response (11-50% of viable tumour cells remaining following 4 cycles of neo-Adjuvant Pembrolizumab) Pathological Stable and/or Progressive disease (greater than 50% viable tumour cells following 4 cycles of Neo-adjuvant Pembrolizumab)

Time frame

Will be assessed at the end of Cycle 4 (each cycle is 21 days) of Neo-adjuvant Pembrolizumab.

Secondary outcomes

Objective response Rate

To estimate objective response rate (ORR) as per investigator assessed RECIST 1.1 criteria

Time frame

Will be assessed at the end of Cycle 4 (each cycle is 21 days) of Neo-adjuvant Pembrolizumab

Disease free survival

To estimate investigator assessed disease free survival (DFS) per RECIST 1.1 criteria

Time frame

From date of drug allocation until the date of first documented recurrence or date of death from any cause, whichever came first, assessed up to 48 months

Overall Survival

To evaluate the overall survival (OS) of the participants.

Time frame

From date of drug allocation until the date of death from any cause, whichever came first, assessed up to 48 months

Locoregional Recurrence

Freedom from locoregional recurrence

Time frame

From date of drug allocation until the date of first documented locoregional recurrence or date of death from any cause, whichever came first, assessed up to 48 months

Other outcomes

Rate of De-escalation of surgery or post-operative radiotherapy following neo-adjuvant pembrolizumab

Change from planned baseline multidisciplinary meeting recommendation. Patient may de-escalate both Post-operative radiotherapy +/- surgery depending on response

Time frame

At the end of 4 cycles of neo-adjuvant pembrolizumab. Each cycle is 21 days.

Pattern of failure

Pattern of failure, assessed using descriptive analysis of percentages of patients in which disease recurrence for the primary endpoint of the study is due to local recurrence, regional recurrence, or distant recurrence

Time frame

From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years following last administration of study drug (4 years total)

Cumulative occurrence of Second Primary Tumours (SPT)

Cumulative occurrence of SPTs for each patient

Time frame

From date of drug allocation until the date of first documented recurrence or date of death from any cause, whichever came first, assessed up to 48 months

18F FDG PET/CT complete metabolic response (CMR) rate

absence FDG uptake of target tumour lesion on 18F FDG PET/CT

Time frame

Assessed at the end of Cycle 4 (each cycle is 21 days)

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Queensland Health

Lead sponsor

Merck Sharp & Dohme LLC

Collaborator

Source ClinicalTrials.gov

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