SMR-3760
Research type
Research Study
Full title
Phase II, open label, single arm study to investigate anti-tumor effect of ixabepilone in patients with locally recurrent or metastatic breast cancer (mBC) selected by the ixabepilone Drug Response Prediction (DRP) after failure of an anthracycline and a taxane.
IRAS ID
289437
Contact name
Amanda Knock
Contact email
Sponsor organisation
Allarity Therapeutics
Eudract number
2020-004610-35
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
SMR-3760, CRO
Duration of Study in the UK
3 years, 5 months, 1 days
Research summary
Summary of Research
This study is a multi-national (Belgium, Germany, UK, Finland and Poland), multi-centre (Approx. 10 sites) open-label, non-randomized, phase II study to investigate the safety and efficacy of ixabepilone in patients with recurrent breast cancer or metastatic breast cancer (the cancer has spread to other parts of the body).
Ixabepilone is approved by the FDA for metastatic and locally advanced breast cancer and is a member of a class of chemotherapy agents called epothilones, which work by preventing the cancer cell from dividing or reproducing, ultimately leading to cancer cell death. Few treatment options are available for patients resistant to other chemotherapy agents such as anthracyclines, taxanes and capecitabine, therefore ixabepilone is an alternative treatment option for late stage breast cancer patients.
Patients who have received a maximum of three prior chemotherapies will have their biopsies screened with the ixabepilone drug response predictor (DRP) assay. The DRP profile will be used to select the patients with high likelihood of responding to ixabepilone. If the DRP score is above >67% and other eligibility criteria are fulfilled, the patient will be included in the clinical study.
Up to 200 patients with sufficient tumour tissue will be screened to include 60 patients with a high likelihood of responding to ixabepilone.
A screening period (≤4 weeks) for tumour assessment and biopsy will be followed by a baseline visit (≤ 2 weeks) where blood and urine samples will be collected as part of the safety assessment along with checking patient’s general health prior to administration of ixabepilone. Patients will receive ixabepilone 40 mg/m2 as a 3-h intravenous infusion on day 1 and attend the site on day 8 and 15 for further health checks. Treatment will be administered on day 1 of a 21 days cycle. Treatment cycles will continue until disease progression or unacceptable toxicity.Summary of Results
This study was a multi-centre, open-label, non-randomized, phase II study of ixabepilone as treatment in patients with locally recurrent or metastatic breast cancer. The patients should have received a maximum of three (3) prior chemotherapies in the metastatic setting. A biopsy from each patient was used for Drug Response Prediction (DRP) assessment to select the patients with high likelihood of response to therapy with ixabepilone.
The study was terminated early due to slow enrolment, at least partially related to COVID restrictions, as well as changes in the study population. Hence, no efficacy results are reported, only safety results.
Sixty-seven doses of ixabepilone in total were administered to 12 participants during the study. The minimum dose administered was 32 mg, the median dose was 58 mg and the maximum was 76.8 mg of ixabepilone.
Two hundred and thirty-two adverse events (AEs) were reported. Fifty percent were Grade 1 (mild; n = 117), 35% Grade 2 (moderate; n = 82), 12% Grade 3 (severe or medically significant but not life threatening; n = 29), and 1% Grade 4 (life-threatening requiring urgent intervention; n = 3). The three Grade 4 events were related to neutropenia. The most common adverse events were blood and lymphatic system disorders (17% of AEs), gastrointestinal disorders (17% of AEs), nervous system disorders (12% of AEs), general disorders and administration site conditions (12% of AEs), and musculoskeletal and connective tissue disorders (10%). Relatedness and severity was not reported for one AE, a pulmonary embolism. One hundred and sixty-seven (72%) AEs were assessed as being related to ixabepilone.There were eight Serious Adverse Events (SAEs) reported in five patients, two alterations of general status in the same patient, two anaemia events in the same patient, and single cases of asthenia, dyspnoea, neutropenia and tremors. All of these, except for one case of alteration of general status, was assessed as being related to ixabepilone. There were no deaths.
Conclusion:
This study was terminated early due to slow enrolment and changes in the study population. No safety concerns were identified with the use of Ixabepilone.REC name
West of Scotland REC 1
REC reference
21/WS/0026
Date of REC Opinion
23 Mar 2021
REC opinion
Further Information Favourable Opinion