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.
- Conditions
- CancerCancer - Head and neckCancer - Breast
- Registration Number
- ACTRN12619001527156
- Lead Sponsor
- The University of Queensland
- Brief Summary
o increase in on-target toxicity seen in first in human combination safety study. A phase 1b dose escalation safety study treating patients with the combination of cetuximab and PCZ has not demonstrated any unexpected toxicity despite reaching full dose cetuximab. Twelve patients with relapsed head and neck SCC, adenoid cystic carcinoma or EGFR over-expressed triple negative breast cancer have received a total of 57 weeks of the combination treatment. No SAEs or grade 3/4 toxicities attributable to the combination have been seen. Toxicity to date has included grade 1 sedation, akathisia and orthostatic hypotension related to PCZ and resolved within 24 hours. Cetuximab-related rash was observed in ~70% of patients who completed trial. No haematologic toxicity due to the drug combination has been recorded.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 14
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
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
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>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.<br>[6-8 weeks from first cetuximab iv]
- Secondary Outcome Measures
Name Time Method