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Trial registered on ANZCTR


Registration number
ACTRN12619001527156
Ethics application status
Approved
Date submitted
15/10/2019
Date registered
5/11/2019
Date last updated
5/11/2019
Date data sharing statement initially provided
5/11/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Testing whether prochlorperazine can be safely used to move anti-cancer therapy targets temporarily to tumour cell surfaces with combination dose increases of cetuximab anti-EGFR antibody.
Scientific title
Open-label Phase I study investigating the safety and efficacy of Cetuximab and prochlorperazine (STEMetil) combination therapy in patients with metastatic Head and Neck Squamous Cell Carcinoma and Triple Negative Breast Cancer (CESTEM study)
Secondary ID [1] 299557 0
None
Universal Trial Number (UTN)
Trial acronym
CESTEM-1
Linked study record
Not applicable

Health condition
Health condition(s) or problem(s) studied:
Cancer 314817 0
Condition category
Condition code
Cancer 313154 313154 0 0
Head and neck
Cancer 313155 313155 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Dose escalation of cetuximab by direct administration for 6 weeks (6 doses). Day 1: Initial cetuximab will be administered as per assigned group, group 1) 50mg/mg2, group 2) 100mg/mg2, group 3) 150 mg/mg2, group 4) 250mg/mg2 and group 5) loading dose 400mg/mg2 (day 1) then 250mg/mg2 cetuximab (5 weekly maintenance doses); delivered via intravenous infusion over 2 hours. Cetuximab is to be delivered via an infusion pump and not via a push or bolus delivery. For dose escalation, 5 groups of two patients with safety review after each two patients. Day 3: Prochlorperazine will be administered at a dose of 0.8 mg/kg, delivered via intravenous infusion over 20 minutes. Day 8: Cetuximab will be given as per assigned group, dose via intravenous infusion over 1 hour. 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 on a weekly basis (as per the Day 8 procedures) for a total of five weeks.

All patient assessment/monitoring is recorded in the patient clinical record including observations, medication charts and clinical notes.
Intervention code [1] 315809 0
Treatment: Drugs
Comparator / control treatment
This is a Phase IB dose escalation safety trial. No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 321682 0

To determine the safety of the combination regimen of cetuximab and prochlorperazine. This is by documenting toxicity using CTCAE V4.0 and recording additional adverse events. Safety is defined as 80% of patients receiving cetuximab and prochlorperazine without any grade IV toxicity.
Timepoint [1] 321682 0
6-8 weeks from first cetuximab iv
Secondary outcome [1] 375885 0
To determine the efficacy, as measured by RECIST response criteria, of combination therapy with cetuximab and prochlorperazine in patients with Head and Neck Squamous Cell Carcinoma (HNSCC) and triple negative breast cancer (TNBC).
Timepoint [1] 375885 0
Once treatment is commenced the patient will have response assessment after every 6 weeks of cetuximab and prochlorperazine therapy. At completion of combinatorial therapy, patients will proceed with 3 monthly response assessment in the first year followed by 4 monthly for a minimum of 18 months from commencement of treatment or until progression, death or close out date, whichever comes first. If first assessment is progressive disease then a follow up safety visit will occur at 30 days. The study is completed when the last patient has been followed for a minimum of 18months or until death.
Secondary outcome [2] 375886 0
To determine the progression free survival (PFS) of prochlorperazine with cetuximab.

Progression free survival will be reported from the time of first study treatment (cetuximab dose) to the date of disease progression of the primary, nodal or primary & nodal disease following the best treatment response, or the development of distant metastases or death. Some patients may have progression at the first RECIST assessment and in these patients this is the date of progression.
Timepoint [2] 375886 0
The study is completed when the last patient has been followed for a minimum of 18months or until death..
Secondary outcome [3] 375887 0
Pharmacokinetic data

PK parameters of prochlorperazine examined include Cmax, Tmax/min, T1/2/min and AUC (0-480/ng/mL.min).
Timepoint [3] 375887 0
Blood collection on Day 3, 30,45 and 60 mins after completion of prochlorperazine delivery. Analysis by end of trial.

Eligibility
Key inclusion criteria
1. Radiological and/or histologically confirmed relapsed Head and Neck Squamous Cell Carcinoma/Triple Negative Breast Cancer/Adenoid Cystic Carcinoma of the head and neck region.

2. Predicted life expectancy of greater than three months

3. Male or female greater than or equal to 18 years of age

4. ECOG performance status 0-2

5. Provide informed consent

6. Able to commit to 4 hours in the clinic and 24 hours without driving and operating machinery
7. Female patients of child bearing potential will be required to have a negative pregnancy test prior to entry on the study and be required to practice an effective form of contraception.
8. TNBC patients: histologically confirmed tumour overexpression of EGFR
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Treatment with any investigational agent within the preceding 4 weeks or within 5 half-lives of the investigational agent, whichever is longer.

2. Known hypersensitivity to EGFR inhibitors.

3. Clinically significant cardiovascular disease (including myocardial infarction,
unstable angina, symptomatic congestive heart failure, serious uncontrolled
cardiac arrhythmia) less than or equal to 1 year before enrolment/randomization.

4. History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or
evidence of interstitial lung disease previous imaging.

5. Eastern Cooperative Oncology Group (ECOG) performance status greater than 2

6. On drugs that cause long QTc


7. History of prolonged QT interval or prolonged QT interval on baseline ECG

8. Systolic blood pressure less than 90mmHg and/or diastolic blood pressure less than 50 mmHg in two consecutive blood pressure readings within the 1 hour prior to study drug administration.

9. Previous reaction to antipsychotic medications

10. Parkinsons disease or other chronic extrapyramidal conditions.

11. Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.

12. Subject (male or female) is 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.

13. High risk for poor compliance.

14. Any uncontrolled concurrent medical condition that may interfere with the
interpretation of study results.


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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Dose escalation. Prochloperazine held at dose of active endocytosis inhibition.
Dose Escalation Study Groups
Cetuximab Dose (mg/mg2), weekly administration for 6weeks
Group 1 (2 patients) - Week 1 - 50 mg/mg2, Week 2-6 - 50 mg/mg2
Group 2 (2 patients) - week 1 - 100 mg/mg2, Week 2-6 - 100 mg/mg2
Group 3 (2 patients) - week 1 - 150 mg/mg2, Week 2-6 - 150 mg/mg2
Group 4 (2 patients) - week 1 - 250 mg/mg2, Week 2-6 - 250 mg/mg2
Group 5 (2 patients) - week 1 - 400 mg/mg2, Week 2-6 - 250 mg/mg2

Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
This is by documenting toxicity using CTCAE V4.0 and recording additional adverse events. Safety is defined as 80% of patients receiving cetuximab and prochlorperazine without any grade IV toxicity.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 14964 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 28250 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 304043 0
University
Name [1] 304043 0
The University of Queensland
Address [1] 304043 0
Level 7, General Purpose South Building (Building 78)
Staff House Road
The University of Queensland
Brisbane, Queensland 4072
Country [1] 304043 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
Level 7, General Purpose South Building (Building 78)
Staff House Road
The University of Queensland
Brisbane, Queensland 4072
Country
Australia
Secondary sponsor category [1] 304234 0
None
Name [1] 304234 0
Address [1] 304234 0
Country [1] 304234 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304534 0
Metro South Hospital and Health Service HREC
Ethics committee address [1] 304534 0
Centres for Health Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Ethics committee country [1] 304534 0
Australia
Date submitted for ethics approval [1] 304534 0
16/11/2016
Approval date [1] 304534 0
06/04/2017
Ethics approval number [1] 304534 0
2017000280/HREC/16/QPAH/825

Summary
Brief summary
The purpose of this study is to determine if a high dose of an anti-nausea drug (called prochlorperazine) is safe to give to patients during chemotherapy treatment, while also seeing if there is a health outcome benefit to patients.

Who is it for?

You may be eligible for this study if you are an adult who has a confirmed head and neck cancer or triple negative breast cancer or an adenoid cystic cancer of the head and neck region.

Study details

All patients in this study will receive a high dose of the anti-nausea medication 3 days after the commencement of chemotherapy. After this, all participants will receive the anti-nausea medication weekly, with their chemotherapy. There will be 5 different doses of the chemotherapy given in combination with the anti-nausea medication to participants depending on when the participant joins the study, with the doses increasing over time and only increasing if the doses pass safety reviews.

It is hoped that this research will help determine if the anti-nausea drug is safe in combination with chemotherapy to treat patients, while also testing whether this has an effect on improving health outcomes.
Trial website
None
Trial related presentations / publications
None
Public notes
None

Contacts
Principal investigator
Name 97298 0
A/Prof Euan Walpole
Address 97298 0
Medical Director – Cancer Services
Princess Alexandra Hospital and Metro South Health and Hospital Service, Division of Cancer Services,
Princess Alexandra Hospital,
Ipswich Road,
Woolloongabba, Qld, 4102. Australia
Country 97298 0
Australia
Phone 97298 0
+61 7 3176 5564
Fax 97298 0
Email 97298 0
Euan.Walpole@health.qld.gov.au
Contact person for public queries
Name 97299 0
A/Prof Euan Walpole
Address 97299 0
Medical Director – Cancer Services
Princess Alexandra Hospital and Metro South Health and Hospital Service, Division of Cancer Services,
Princess Alexandra Hospital,
Ipswich Road,
Woolloongabba, Qld, 4102. Australia
Country 97299 0
Australia
Phone 97299 0
+61731765564
Fax 97299 0
Email 97299 0
Euan.Walpole@health.qld.gov.au
Contact person for scientific queries
Name 97300 0
Dr Fiona Simpson
Address 97300 0
Level 6 West, Translational Research Institute
The University of Queensland Diamantina Institute.
Princess Alexandra Hospital
University of Queensland

Brisbane, QLD 4102
Country 97300 0
Australia
Phone 97300 0
+61 0422721656
Fax 97300 0
Email 97300 0
f.simpson@uq.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified safety data and pharmacokinetic analysis
When will data be available (start and end dates)?
Data will be available from Dec2020

Confidential clinical trial data is kept for 15 years after completion and will not be shared – charts of patients with a clinical trial highlight are kept for this via hospital medical records. The extracted de-indentified safety and pharmacokinetic data will be maintained in secure location in UQ and will be published (no end date for availability).
Available to whom?
All
Available for what types of analyses?
Scientific
How or where can data be obtained?
De identified publication of data via scientific journal. Safety data will be described as incidence per number of patients and severity. Other data such as PK will be fully analysed and represented in graphical form with statistical parameters.
What supporting documents are/will be available?
No other documents available
Summary results
No Results