Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000197437p
Ethics application status
Not yet submitted
Date submitted
24/01/2025
Date registered
20/02/2025
Date last updated
20/02/2025
Date data sharing statement initially provided
20/02/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Immunotherapy in Perineural Spread of Cutaneous Squamous Cell Carcinoma - IPERCS
Scientific title
A single arm, phase II trial of Cemiplimab in Head and Neck Cutaneous Squamous Cell Carcinoma with Large Nerve Perineural Spread
Secondary ID [1] 313805 0
NIL Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Skin Cancer 336441 0
Cutaneous Squamous Cell Carcinoma 336442 0
Condition category
Condition code
Cancer 332961 332961 0 0
Other cancer types
Cancer 332962 332962 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single arm, nonrandomised
Cemiplimab intravenous 350mg every three weeks for 8 cycles.
Patients will attend the day oncology unit at their treating institution for administration of Cemiplimab 350mg every 3 weeks for a period of 24 weeks. Patient will be monitored as per industry standards and guidelines.
Patients will be assessed for response via medical imaging. The mode of medical imaging to be used in this study is Computer Tomography (CT), Positron Emission Tomography (PET/CT
and Magnetic Resonance Imaging (MRI) with contrast.
These modes of imaging require a contrast dye which is administered intravenously.
The amount of contrast needed can vary dependant on patient weight, but approximately 30-120ml of contrast is needed.
A CT scan can take up to 30 mins to perform
An MRI can take up to 30 mins to perform
All imaging is performed by a qualified radiologist at the patient's treating institution. Imaging scans are required at screening, 6 weeks and 12 weeks during the treatment phase.
Imaging is required every 3 months during for follow up phase until disease progression, withdrawal of consent of death.
Intervention code [1] 330393 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 340501 0
To estimate the efficacy of Cemiplimab in patients with large nerve perineural spread from cSCC, as assessed by landmark progression free survival (PFS)
Timepoint [1] 340501 0
Every available time point and as a change from baseline. Timepoints: Baseline, Week 6 and Week 12. Post-intervention commencement and every 3 months following completion of Cemiplimab for a maximum of three years until disease progression, withdrawal of consent or death.
Secondary outcome [1] 445128 0
Disease Control Rate (DCR) as per Modified RANO criteria
Timepoint [1] 445128 0
Every available time point and as a change from baseline Baseline, week 6, week 12 and week 24 then every three months post intervention dose until disease progression, withdrawal of consent or death.
Secondary outcome [2] 444282 0
To estimate the overall response rate (ORR) as per Modified RANO criteria
Timepoint [2] 444282 0
Baseline, week 6, week 12 and week 24 then every three months post intervention dose until disease progression, withdrawal of consent or death.

Eligibility
Key inclusion criteria
1. Histologically confirmed history of cutaneous cell carcinoma (cSCC)
2. Large Nerve-Perineural Spread (LN-PNS) defined as clinical and /or radiologic involvement of named nerves (UICC 2015 )
3. Stage III-IV cSCC as defined by AJCC8th edition
4. Measurable LN-PNS on baseline MRI
5. Absence of distant metastatic disease on baseline imaging
6. ECOG performance status 0-1
7. Participants must have adequate organ function as defined below:
Laboratory Value
Haematological
Absolute neutrophil count (ANC): equal to 1500 cells/µL without granulocyte colony-stimulating factor (G- CSF) support within 2 weeks prior to the first dose of study treatment
Platelets: equal to 100 000/µL
Haemoglobin: equal to 9 g/dL or equal to 5.6 mmol/L. Participants are eligible if levels are reached after blood transfusion.
Renal: a Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) equal to1.5 × ULN OR equal to 45 mL/min for participants with creatinine levels
greater than 1.5 × institutional ULN
Hepatic: bTotal bilirubin equal to 1.5 × ULN OR direct bilirubin equal to ULN for participants with total bilirubin levels greater than 1.5 × ULN
AST: (SGOT) and ALT
(SGPT) equal to 2.5 × ULN
Coagulation: international normalized ratio (INR)
OR PT and aPTT equal to 1.5 × ULN unless participant is receiving anticoagulant therapy as long as prothrombin time (PT) or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants
a. Creatinine clearance should be calculated per institutional standard.
b. For participants with Gilbert's disease, total bilirubin may be greater than 1.5 × ULN; however, direct bilirubin must be normal.
c. Partial thromboplastin time (PTT) may be performed if the local laboratory is unable to perform aPTT.
8. Participants must have a life expectancy of greater than 6 months
9. Be at least 18 years of age
10. Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hrs prior to receiving the first dose of medication
11. Female participants of childbearing potential must agree to use a highly effective method of contraception during the treatment period and for at least 120 days after the last dose.
12. The participant or legal representative must be willing and able to sign to provide written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participant with distant metastatic cSCC
2. Participants with any prior allogeneic solid organ or hematopoietic stem cell transplantations are excluded.
3. 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).
4. Participant has received prior systemic anti-cancer therapy including investigational agents for cSCC.
5. Participant has received prior radiotherapy to the target lesion.
6. Participant has a contraindication to MRI
7. 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.
8. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments (eg, with use of disease-modifying agents, anticoagulants, corticosteroids or immunosuppressive drugs)., which may suggest risk for immune-related adverse events (irAEs) or has a diagnosis of immunodeficiency disorders (such as organ transplantation or hematologic malignancies associated with immune suppression).
9. 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 to the first dose of trial drug.
10. Has uncontrolled infection with human immunodeficiency virus, hepatitis B, or hepatitis C infection; or has a diagnosis of immunodeficiency
a. Patients with known HIV infection who have controlled infection (undetectable viral load (HIV RNA PCR) and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted.
b. Patients with hepatitis B (HBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection and receiving anti-viral therapy for hepatitis B) are permitted. Patients must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug.
c. Patients who are hepatitis C virus antibody positive (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) may be enrolled into the study.
11. Participant has a diagnosis and/or has been treated for additional malignancy within the past 3 years prior to allocation.
12. Participant has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
13. 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.
14. 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.
15. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
The estimate of the landmark PFS along with its 95% CI.
Counts, percentages and the corresponding 95% confidence intervals (CIs) of participants with AEs will be provided

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/06/2025
Actual
Date of last participant enrolment
Anticipated
1/07/2025
Actual
Date of last data collection
Anticipated
31/12/2030
Actual
Sample size
Target
22
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 27523 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 43636 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 318272 0
Commercial sector/Industry
Name [1] 318272 0
Regeneron Pharmaceuticals, Inc
Country [1] 318272 0
United States of America
Primary sponsor type
Government body
Name
Metro South Hospital and Health Services
Address
Country
Australia
Secondary sponsor category [1] 320659 0
None
Name [1] 320659 0
Address [1] 320659 0
Country [1] 320659 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 316912 0
Metro South Human Research Ethics Committee
Ethics committee address [1] 316912 0
Ethics committee country [1] 316912 0
Australia
Date submitted for ethics approval [1] 316912 0
13/03/2025
Approval date [1] 316912 0
Ethics approval number [1] 316912 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 139410 0
A/Prof Rahul Ladwa
Address 139410 0
Prinicess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba, Qld, 4102
Country 139410 0
Australia
Phone 139410 0
+61 07 3176 3962
Fax 139410 0
Email 139410 0
[email protected]
Contact person for public queries
Name 139411 0
Kym Bessell
Address 139411 0
Prinicess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba, Qld, 4102
Country 139411 0
Australia
Phone 139411 0
+61 07 3176 3962
Fax 139411 0
Email 139411 0
[email protected]
Contact person for scientific queries
Name 139412 0
Rahul Ladwa
Address 139412 0
Prinicess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba, Qld, 4102
Country 139412 0
Australia
Phone 139412 0
+61 07 3176 2111
Fax 139412 0
Email 139412 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• On a case-by-case basis, at the discretion of the Primary Sponsor


Conditions for requesting access:
• -

What individual participant data might be shared?
• Only relevant de-identified individual participant data collected during the trial may be used for statistical, translational research and publication purposes

What types of analyses could be done with individual participant data?
• PFS at 12 months: defined as the proportion of patients at 12 months without progression or death from first day of study treatment.

When can requests for individual participant data be made (start and end dates)?
From:
immediately following publication, no end date


To:
-

Where can requests to access individual participant data be made, or data be obtained directly?
• Access to data is subject to approval by the Principal Investigator and or Sponsor.
Subject to approval by PI - email: [email protected]

Are there extra considerations when requesting access to individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.