A phase 2 study of neoadjuvant Pembrolizumab in cutaneous squamous cell carcinoma (cSCC).
- Conditions
- CancerHead and Neck CancerCutaneous Squamous Cell CancerCancer - Head and neck
- Registration Number
- ACTRN12621000901808
- Lead Sponsor
- Metro South Hospital and Health Services
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 47
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 who is a candidate for a complete resection.
Participants must have measurable disease based on RECIST 1.1.
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 collected within 10 days prior to the start of treatment.
Participants must have a tissue sample adequate for translational research.
Participants must have a life expectancy of greater than 6 months.
Be at least 18 years of age on the day of signing the informed consent.
Female participants: Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of trial medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) OR
- A WOCBP who agrees to use an adequate method of contraception during the treatment period and for at least 120 days after the last dose of study treatment.
The participant (or legally acceptable representative if applicable) must be willing and able to provide written informed consent for the trial. The participant may also provide consent for Future Biomedical Research. However the participant may participate in the main trial without participating in Future Biomedical Research.
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 celltransplantations 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).
Participant has received prior systemic anti-cancer therapy including investigational agents for cSCC.
Participant has received prior radiotherapy to the target lesion.
Participant has received a live vaccine within 30 days prior to the first dose of trial drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed-virus vaccines and are allowed; however, intranasal influenza vaccines(eg, FluMist®) are live- attenuated vaccines and are not allowed.
Participant is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment.
Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs) or has a diagnosis of immunodeficiency disorders (such as HIV disease or organ transplantation or hematologic malignancies associated with immune suppression).
Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of trial drug.
Participant has a diagnosis and/or has been treated for additional malignancy within the past 3 years prior to allocation.
- Participants with cSCC of the skin that have undergone potentially curative therapy are not excluded if not related to current diagnosis.
- Participants with basal cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer or melanoma in situ) that have undergone potentially curative therapy are not excluded.
- Participants with low-risk early-stage prostate cancer, defined as below are not excluded: Stage T1c or T2a with a Gleason score 6 or less, and a prostate-specific antigen (PSA) (10 ng/ml or less) either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to trial allocation.
Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (eg, with use of disease-modifying agents, anticoagulants, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
Participant has
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Changes in pathological tumour response from baseline to end of 4 cycles of study drug pre-surgery. Response will be determined by review of pathological specimen taken at surgical resection.<br><br>Response to the neo-adjuvant treatment will determine whether patient proceeds to surgery alone or surgery plus radiotherapy.[ As a change from baseline to end of 4th cycle of study drug (12 weeks post-intervention commencement)]
- Secondary Outcome Measures
Name Time Method Composite Changes in pathological and/or clinical tumour response from baseline until end of intervention and at relapse of disease. Response will be measured via clinical assessment by clinician, pathological reviews and radiological imaging using PET Scans and CT Scans.<br>[ Every available time point and as a change from baseline.<br>Timepoints:<br>Baseline, Week 7 and Week 15 post-intervention commencement and every 3 months during adjuvant pembrozilumab (total 17 cycles), every 4 months following completion of adjuvant pembro for a maximum of two years and at relapse of disease]