Description:
The purpose of this study is to determine the highest dose of CXD101 (a novel histone
deacetylase inhibitor) that can be safely administered to patients with advanced tumours. The
study will also investigate the use of HR23B expression in tumour as a biomarker of response
to treatment with CXD101. Patients with solid tumours, lymphoma and myeloma can be considered
for this study.
Title
- Brief Title: Phase 1 Trial of CXD101 in Patients With Advanced Cancer
- Official Title: Phase 1 Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CXD101 Given Orally (Twice Daily Dosing for 5 Consecutive Days in a 21-day Period) in Patients With Advanced Malignancies Expressing the Biomarker HR23B
Clinical Trial IDs
- ORG STUDY ID:
CXD101-0901
- SECONDARY ID:
2009-012743-42
- NCT ID:
NCT01977638
Conditions
Interventions
Drug | Synonyms | Arms |
---|
CXD101 | AZD9468 | CXD101 |
Purpose
The purpose of this study is to determine the highest dose of CXD101 (a novel histone
deacetylase inhibitor) that can be safely administered to patients with advanced tumours. The
study will also investigate the use of HR23B expression in tumour as a biomarker of response
to treatment with CXD101. Patients with solid tumours, lymphoma and myeloma can be considered
for this study.
Detailed Description
Patients will be treated with CXD101 administered orally starting at 1mg twice a day (ie:
2mg/day). Dose escalation will proceed according to a standard 3+3 phase 1 scheme. Adverse
experiences will be evaluated according to the NCI Common Terminology Criteria for Adverse
Events, version 4.0. Dose escalation will continue until dose limiting toxicity is
encountered in >1/3rd of patients at any dose level. The dose level below this will be
determined to be the maximum tolerated dose. Patients will be treated, at the discretion of
the Principal Investigator, until disease progression, unacceptable toxicity or the
withdrawal of consent. At the maximum tolerated dose a further 20 patients, defined by tumour
HR23B expression will be enrolled.
Trial Arms
Name | Type | Description | Interventions |
---|
CXD101 | Experimental | Dose escalation study of CXD101 administered orally twice daily for 5 consecutive days in every 21 day cycle. Starting dose 1mg twice daily (2mg/day). | |
Eligibility Criteria
Inclusion Criteria:
1. Age ≥ 18 years.
2. Life expectancy of at least 12 weeks.
3. ECOG performance score of ≤ 1
4. Histologically or cytologically confirmed malignant tumour with the potential to
benefit from HDAC inhibitor therapy.
5. High HR23B expressing tumour sample on IHC (expansion cohort only).
6. Evaluable disease.
7. The patient is willing and able to comply with the protocol for the duration of the
study, including scheduled follow-up visits and examinations.
8. Patients must have recovered from effects of prior treatments, including surgeries
(persistent grade 1 toxicities are permitted at the discretion of the Chief
Investigator).
9. Female patients with reproductive potential must have a negative urine or serum
pregnancy test within 14 days prior to start of trial. Both women and men must agree
to use a medically acceptable method of contraception throughout the treatment period
and for 16 weeks after discontinuation of treatment. Oral contraception and parenteral
hormonal contraceptives (patches, injectables and implants) that may be affected by
enzyme-inducing drugs should only be used in combination with a barrier method. All
males with partners of childbearing potential or whose partners are pregnant must use
barrier contraception for the duration of dosing and for 16 weeks post-dosing.
10. Able to give written (signed and dated) informed consent.
11. Haematological and biochemical indices within acceptable ranges as detailed in study
protocol.
Exclusion Criteria:
1. Pregnant or breast-feeding women or women of childbearing potential unless effective
methods of contraception are used.
2. Other psychological, social or medical condition, physical examination finding or a
laboratory abnormality that the Investigator considers would make the patient a poor
trial candidate or could interfere with protocol compliance or the interpretation of
trial results.
3. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or
HIV.
4. Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or use
of other investigational agents within 28 days prior to trial entry (or a longer
period depending on the defined characteristics of the agents used). Limited field
radiotherapy to an isolated lesion in bone or soft tissue must be completed 2 weeks
prior to trial entry.
5. Patients must not receive any concurrent anti-cancer therapy, including
investigational agents, while on-study. Patients may continue the use of
bisphosphonates for bone disease or corticosteroids providing the dose is stable
before and during the trial.
6. Major surgery within 4 weeks of starting the study.
7. Co-existing active infection requiring parenteral antibiotics or serious concurrent
illness deemed clinically significant.
8. Patients with known brain metastases, unless these are shown to be stable
(symptomatically and/or radiologically) over a period of 2 months or more.
9. History of refractory nausea and vomiting, chronic GI diseases (eg: inflammatory bowel
disease) or significant bowel resection that would preclude adequate absorption of
oral medication.
10. Patients who are unable to swallow oral medication.
11. Patients with corrected QT interval >450msec.
12. Persistent grade 2 or greater toxicities from any cause.
13. Previous treatment with a HDAC inhibitor.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | To determine the maximum tolerated dose of CXD101 administered twice daily for 5 consecutive days every 21 days |
Time Frame: | 18 months |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | To determine the pharmacokinetic (PK) profile of CXD101 following single and multiple dosing |
Time Frame: | 18 months |
Safety Issue: | |
Description: | |
Measure: | To enable a preliminary assessment of the anti-tumour activity of CXD101 |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Measure: | To evaluate the tissue expression of the biomarker HR23B |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Measure: | To assess the pharmacodynamic effect of CXD101 |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Oxford University Hospitals NHS Trust |
Trial Keywords
- Advanced solid tumours
- Lymphoma
- Myeloma
Last Updated
October 19, 2020