None listed
Conditions
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.
Interventions
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,
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.
Sponsors
The University of Queensland
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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.
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.
Outcome results
None listed