A phase 2 study of neoadjuvant Pembrolizumab in cutaneous squamous cell carcinoma (cSCC).
A phase 2 study of de-escalation in resectable, locally advanced cutaneous squamous cell carcinoma with the use of neoadjuvant Pembrolizumab.
Metro South Hospital and Health Services
47 participants
Jun 29, 2022
Interventional
Conditions
Summary
The main purpose of this research project is to see if immunotherapy drug pembrolizumab may shrink the tumour prior to surgery and potentially reduce the requirement of subsequent treatment such as post-operative radiotherapy (PORT) in patients with Squamous Cell Carcinoma (SCC) of the skin. Who is it for? You may be eligible for this study if you are aged 18 years or older, have a confirmed diagnosis of invasive SCC, and are a candidate for surgical resection and/or post-operative radiotherapy. Study details All participants will receive pembrolizumab intravenously once every 3 weeks for a total of 4 cycles prior to planned surgery. Depending on the effect of pembrolizumab, participants will either receive surgery, surgery and PORT, or neither, depending on the proportion of tumour cells seen on biopsy. All participants will subsequently have post-operative pembrolizumab for 12 months in three weekly visits. Your participation in this research project consists of: • A screening period of up to 28 days: After you sign this Participant informed consent form, testing will be done to determine if this research project is suitable for you. • A treatment period of approximately 64 weeks and • An end of treatment visit, approximately 30 days after the completion of the study drug treatment period. This may be because you have completed the treatment period, or you or your doctor has decided to stop you receiving the study treatment. • A post-treatment follow-up period of approximately up to 2 years or until your skin cancer returns or the study ends It is hoped that this study will help us understand whether pembrolizumab can shrink the tumour, in which patients this may be more likely to occur, and any side effects that may be experienced during this study. This may help to treat other patients with SCC of the skin in future and reduce the requirement for surgery or radiotherapy.
Eligibility
Inclusion Criteria12
- 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.
Exclusion Criteria21
- 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 a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Participant has an active infection requiring systemic therapy.
- Participant has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
- Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- Participant has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the trial.
- Participant is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
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Interventions
Initial: Pembrolizumab - 200mg, every three weeks, Intravenous Infusion, 4 cycles Patients will be assessed for response via medical imaging and this will determine whether patients will undergo surgery plus or minus external beam radiation therapy (XRT). Patients will be deemed for surgery if they have not had a complete clinical and radiological response (based on physical examination and radiological imaging using PET and/or CT Scan). Surgery will be scheduled for 3 weeks after the 4th cycle of pembrolizumab. Patients who, at surgery, demonstrate nodal metastases and/or those with greater than 10% viable tumour cells post-resection will receive Post-operative radiotherapy. Patients who demonstrate a complete clinical and radiological response (based on physical examination and radiological imaging using PET and/or CT Scan), will undergo a series of biopsies to confirm a complete pathological response. Patients will be referred for surgical resection plus or minus radiotherapy if the biopsies do not indicate a complete pathological response. Patients requiring Radiation therapy will commence 4-6 weeks following surgery. The radiation therapy dose will be 50-66 Gray, 25-33 treatments, 5 days a week for 5-7 weeks in accordance with the Head and Neck Consensus Guidelines. The dose and duration will be determined by the pathological response at surgery. Post Surgery/Post XRT: Pembrolizumab - 200mg, every three weeks, Intravenous Infusion, 17 cycles. Patients will attend the day oncology unit at their treating institution for administration of all study therapies as applicable. The overall duration of pembrolizumab is 87 weeks (4 treatments, given every 3 weeks prior to surgery; 17 treatments, given every three weeks post surgery/radiotherapy).
Locations(3)
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ACTRN12621000901808