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Trial registered on ANZCTR


Registration number
ACTRN12624000917538
Ethics application status
Approved
Date submitted
26/06/2024
Date registered
29/07/2024
Date last updated
29/07/2024
Date data sharing statement initially provided
29/07/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy and safety of cetuximab and prochlorperazine combined for solid organ transplant patients with advanced Cutaneous Squamous Cell Carcinoma: CetPro study
Scientific title
Efficacy and safety of cetuximab and prochlorperazine combined for solid organ transplant patients with advanced Cutaneous Squamous Cell Carcinoma: CetPro study
Secondary ID [1] 312412 0
none
Universal Trial Number (UTN)
Trial acronym
CetPro
Linked study record

Health condition
Health condition(s) or problem(s) studied:
skin cancer

 334223 0
solid organ transplant recipients 334224 0
Condition category
Condition code
Cancer 330893 330893 0 0
Non melanoma skin cancer
Surgery 331020 331020 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Efficacy and safety of cetuximab and prochlorperazine combined
Day 1: Cetuximab will be administered at 500mg/mg2 via intravenous infusion.
Day 8: Cetuximab will be administered at 250mg/mg2 via intravenous infusion. Prochlorperazine will then be administered at a dose of 0.8mg/kg via intravenous infusion 1 hour after the completion of cetuximab. Cetuximab and prochlorperazine (0.8mg/kg) will be administered in combination on a weekly basis for a total of 6 weeks (Day 8, Day 15, Day 22, Day 29, D36, D43) (total treatment period of 7 weeks).
Depending on the response this treatment can be reconducted for a new period of 6 weeks.
All patient assessment/monitoring is recorded in the patient clinical record including observations, medication charts and clinical notes.
If necessary, depending on clinician decision, antihistamines and corticosteroids will be administered 30 min before cetuximab administration: Oral Loratadine 10mg and
Intravenous hydrocortisone 100mg.
Intervention code [1] 328914 0
Treatment: Drugs
Intervention code [2] 328915 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 338648 0
To determine the disease control rate (DCR) as a measure of efficacy.
Timepoint [1] 338648 0
at 6- and 12-weeks post-commencement of combination treatment (Cetuximab + PCZ).
Secondary outcome [1] 436835 0
To determine the clinical efficacy assessed via tumour size
Timepoint [1] 436835 0
at 6- and 12-weeks post-commencement of combination treatment (Cetuximab+PCZ).
Secondary outcome [2] 436836 0
Overall survival advantage with the addition of prochlorperazine to cetuximab
Timepoint [2] 436836 0
The study is completed when the last patient has been followed for a minimum of 18 weeks or until death.
Secondary outcome [3] 437422 0
To determine the Objective Response Rate (ORR) as a measure of efficacy
Timepoint [3] 437422 0
at 6 and 12 weeks for the combination treatment (Cetuximab+PCZ).
Secondary outcome [4] 437423 0
To determine the progression free survival (PFS) advantage with the addition of prochlorperazine to cetuximab
Timepoint [4] 437423 0
The study is completed when the last patient has been followed for a minimum of 18 weeks or until death.
Secondary outcome [5] 437424 0
To establish the safety of administering cetuximab in combination with prochlorperazine.
Timepoint [5] 437424 0
The study is completed when the last patient has been followed for a minimum of 18 weeks or until death.
Secondary outcome [6] 437425 0
To analyse the Epidermal Growth Factor Receptor (EGFR) and its uptake pre- and post-treatment.
Timepoint [6] 437425 0
Pre-screening biopsy before commencement of combination treatment (Cetuximab+PCZ)., and biopsy at Day8
Secondary outcome [7] 437426 0
To characterize at a subcellular level advanced cSCC in SOTRs with long-read DNA sequencing.
Timepoint [7] 437426 0
Before commencement of combination treatment (Cetuximab+PCZ).
Secondary outcome [8] 437427 0
Number of patients becoming eligible for surgery
Timepoint [8] 437427 0
at 6- and 12-weeks post-commencement of combination treatment (Cetuximab + PCZ).

Eligibility
Key inclusion criteria
1. Radiological and/or histologically confirmed advanced cutaneous SCC
2. EGFR staining positively on tumour biopsy.
3. At screening, non-suitable for or refusing surgery, radiotherapy or immunotherapy
4. Accessible tumour for biopsy.
5. Solid organ transplant recipient of more than 1 year.
6. Life expectancy of greater than three months.
7. Male or female, at least 18 years of age or more.
8. ECOG (Eastern Cooperative Oncology Group) performance status 0-2.
9. Can provide informed consent and are willing to participate for the duration of the study and to follow study procedures.
10. Able to commit to a 4-hour clinic visit and to abstaining from driving and operating machinery for a 24-hour period.
11. Female patients of childbearing potential will be required to have a negative pregnancy test prior to enrolment and be required to practice an effective form of contraception. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test at enrolment prior to each treatment cycle and use a highly effective contraceptive method including the oral contraceptive pill (OCP) or an intrauterine hormone device (IUD) commencing at screening and until at least 1 month following the last dose of Cetuximab. Females who are abstinent from heterosexual intercourse as part of their usual lifestyle do not need to use contraception.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Treatment with any investigational agent within the preceding 4 weeks from date of consent, or within 5 half-lives of the investigational agent, whichever is longer.
2. Unknown EGFR status and no lesion accessible for biopsy.
3. Known hypersensitivity to EGFR inhibitors.
4. Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) less than one year before enrolment.
5. History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease previous imaging.
6. ECOG performance status more than 2
7. Taking medications with a known risk of prolonging QTc interval
8. History of prolonged QT interval or prolonged QT interval on baseline screening electrocardiogram (ECG) (standard 12-lead (ECG) parameters after 5 minutes resting in supine position with PR longer than 120 milliseconds (ms) and less than 220 ms, QRS less than 120 ms, QTcF egal to 450 ms for males and egal to 470 ms for females, and otherwise normal ECG.)
9. Systolic blood pressure less than 90mmHg and/or diastolic blood pressure less than 50 mmHg in two consecutive blood pressure readings within the hour prior to study drug administration.
10. Previous reaction to antipsychotic medications, antihistamines, and steroids.
11. Parkinson’s disease or other chronic extrapyramidal conditions.
12. Subject is pregnant or breast feeding or planning to become pregnant within 6 months after the end of treatment.
13. Subject (male or female) of childbearing age not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment.
14. High risk for poor compliance.

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
Safety/efficacy
Statistical methods / analysis
10 patients from the Transplant Skin Clinics or the Queensland Head and Neck Cancer Centre or Cancer Services Oncology within the Princess Alexandra Hospital will be recruited.
We have scheduled an interim analysis after enrolling five patients for evaluation.
Safety analyses will include all participants who received at least one dose of study treatment.
Efficacy analyses will be by intention-to-treat and include all participants recruited who received at least one dose,
Time to event data will be summarised using the Kaplan Meier method including all participants
recruited.
Measures of effect will be reported with 2-sided 95% confidence intervals calculated with
appropriate methods.
Full Analysis Set: Suitable regression models will be used to test the effects of baseline characteristics on key endpoints, e.g. location, type of transplant, pathological characteristics... Logistic regression will be used for dichotomous endpoints. Cox proportional hazards models will be used for time-to-event
endpoints. Sensitivity analyses will be used to assess effects on the findings and conclusions of excluding
participants who were deemed ineligible, unevaluable, or did not receive study treatment.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2024
Actual
Date of last participant enrolment
Anticipated
28/11/2025
Actual
Date of last data collection
Anticipated
17/07/2026
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 26733 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 42780 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 316823 0
Government body
Name [1] 316823 0
Metro South Health Research Support Scheme (MSH RSS)
Country [1] 316823 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
Country
Australia
Secondary sponsor category [1] 319052 0
None
Name [1] 319052 0
Address [1] 319052 0
Country [1] 319052 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315593 0
Metro South Human Research Ethics Committee
Ethics committee address [1] 315593 0
https://metrosouth.health.qld.gov.au/research/about-us/hrec
Ethics committee country [1] 315593 0
Australia
Date submitted for ethics approval [1] 315593 0
16/03/2023
Approval date [1] 315593 0
26/02/2024
Ethics approval number [1] 315593 0
94554

Summary
Brief summary
This study aims to evaluate the effectiveness and safety of combining prochlorperazine (PCZ) (Stemetil®) with cetuximab, an anti-EGFR (Epidermal Growth Factor Receptor) antibody used in cutaneous squamous cell carcinoma (cSCC) treatment.
Who is it for?
You may be eligible for this study if you are a male or female age 18 or older. Additionally, you are a solid organ transplant recipient (such as kidney, liver, lung, or heart recipients) with non-operable or locally advanced or metastatic cutaneous squamous cell carcinoma (cSCCC) who are not suitable for surgery, radiotherapy alone, or immune checkpoint inhibitors.
Study details
All participants will be premedicated with antihistamines and corticosteroids before receiving an intravenous infusion of 0.8mg/kg of prochlorperazine with cetuximab once per week for 6 weeks, extendable depending on tolerance and response.
As each study follow up, participant's medical record will be reviewed for disease progression, toxicity and survival.
It is hoped that the findings from this study will open a new therapeutic strategy for advanced cSCCs in Solid Organ Transplant Recipients without compromising their allograft.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 135178 0
Prof Kiarash Khosrotehrani
Address 135178 0
Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba QLD 4102
Country 135178 0
Australia
Phone 135178 0
+61 7 3443 7399
Fax 135178 0
Email 135178 0
[email protected]
Contact person for public queries
Name 135179 0
Dr Dousset Lea
Address 135179 0
Frazer Institute, The University of Queensland, 37 Kent Street, Woolloongabba QLD 4102
Country 135179 0
Australia
Phone 135179 0
+61734437088
Fax 135179 0
Email 135179 0
[email protected]
Contact person for scientific queries
Name 135180 0
Dr Dousset Lea
Address 135180 0
Frazer Institute, The University of Queensland, 37 Kent Street, Woolloongabba QLD 4102
Country 135180 0
Australia
Phone 135180 0
+61734437088
Fax 135180 0
Email 135180 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.