Advanced CancerPhase 1NCT01977638
Phase 1 Trial of CXD101 in Patients With Advanced Cancer
A Phase 1 study testing CXD101 in people with Advanced Cancer, run by Oxford University Hospitals NHS Trust at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancer
- What is being tested?
- CXD101
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 14 Feb 2014to 14 Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years.
- Life expectancy of at least 12 weeks.
- ECOG performance score of ≤ 1
- Histologically or cytologically confirmed malignant tumour with the potential to benefit from HDAC inhibitor therapy.
- High HR23B expressing tumour sample on IHC (expansion cohort only).
- Evaluable disease.
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- The patient is willing and able to comply with the protocol for the duration of the study, including scheduled follow-up visits and examinations.
- Patients must have recovered from effects of prior treatments, including surgeries (persistent grade 1 toxicities are permitted at the discretion of the Chief Investigator).
- 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.
- Able to give written (signed and dated) informed consent.
- Haematological and biochemical indices within acceptable ranges as detailed in study protocol.
Who cannot join
- Pregnant or breast-feeding women or women of childbearing potential unless effective methods of contraception are used.
- 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.
- Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.
- 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.
- 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.
- Major surgery within 4 weeks of starting the study.
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- Co-existing active infection requiring parenteral antibiotics or serious concurrent illness deemed clinically significant.
- Patients with known brain metastases, unless these are shown to be stable (symptomatically and/or radiologically) over a period of 2 months or more.
- 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.
- Patients who are unable to swallow oral medication.
- Patients with corrected QT interval >450msec.
- Persistent grade 2 or greater toxicities from any cause.
- Previous treatment with a HDAC inhibitor.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Oxford University Hospitals NHS Trust
Oxford, Oxfordshire, OX3 7LE
About this study
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
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.
Read the 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.
- Conditions
- Advanced Cancer
- Being tested
- CXD101
- Keywords
- Advanced solid tumours, Lymphoma, Myeloma
- Medical subject headings
- Lymphoma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CXD101Drug
Also called AZD9468
Capsules, administered orally
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: CXD101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose of CXD101 administered twice daily for 5 consecutive days every 21 days
Measured: 18 months
Secondary outcomes (4)
To determine the pharmacokinetic (PK) profile of CXD101 following single and multiple dosing
Measured: 18 months
To enable a preliminary assessment of the anti-tumour activity of CXD101
Measured: 24 months
To evaluate the tissue expression of the biomarker HR23B
Measured: 24 months
To assess the pharmacodynamic effect of CXD101
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2013 (estimated)
- Study start14 Feb 2014
- Primary completion8 Oct 2019
- Study completion14 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oxford University Hospitals NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oxford, National Institute for Health Research, United Kingdom, Cancer Research UK
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01977638
- Sponsor's protocol ID
- CXD101-0901
- Other IDs
- 2009-012743-42, 2009
- Status last verified
- Oct 2021
- First submitted
- 5 Nov 2013
- Last updated
- 18 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Booth SW, Eyre TA, Whittaker J, Campo L, Wang LM, Soilleux E, Royston D, Rees G, Kesavan M, Hildyard C, Kazmi F, La Thangue N, Kerr D, Middleton MR, Collins GP. A Phase 2a cohort expansion study to assess the safety, tolerability, and preliminary efficacy of CXD101 in patients with advanced solid-organ cancer expressing HR23B or lymphoma. BMC Cancer. 2021 Jul 23;21(1):851. doi: 10.1186/s12885-021-08595-w.
PubMed 34301221
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01977638
- Acronym / sponsor ID
- CXD101-0901
- Conditions
- Advanced Cancer
- Keywords
- Advanced solid tumours, Lymphoma, Myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Oxford University Hospitals NHS TrustUniversity, hospital or other
- Collaborators
- University of Oxford, National Institute for Health Research, United Kingdom, Cancer Research UK
- Study start
- 14 Feb 2014 (actual)
- Primary completion
- 8 Oct 2019 (actual)
- Study completion
- 14 Oct 2022 (actual)
- First posted
- 7 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CXD101 | Experimental | Drug: CXD101Dose escalation study of CXD101 administered orally twice daily for 5 consecutive days in every 21 day cycle. Starting dose 1mg twice daily (2mg/day). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age ≥ 18 years.
- Life expectancy of at least 12 weeks.
- ECOG performance score of ≤ 1
- Histologically or cytologically confirmed malignant tumour with the potential to benefit from HDAC inhibitor therapy.
- High HR23B expressing tumour sample on IHC (expansion cohort only).
Key exclusion criteria (13 listed)
- Pregnant or breast-feeding women or women of childbearing potential unless effective methods of contraception are used.
- 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.
- Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CXD101Also: AZD9468Capsules, administered orally | Drug | CXD101 |
Primary outcome
To determine the maximum tolerated dose of CXD101 administered twice daily for 5 consecutive days every 21 days
Time frame: 18 months
4 secondary outcomes
To determine the pharmacokinetic (PK) profile of CXD101 following single and multiple dosing
Time frame: 18 months
To enable a preliminary assessment of the anti-tumour activity of CXD101
Time frame: 24 months
To evaluate the tissue expression of the biomarker HR23B
Time frame: 24 months
To assess the pharmacodynamic effect of CXD101
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2022.
- Derived from this study: PubMed 34301221Booth SW, Eyre TA, Whittaker J, Campo L, Wang LM, Soilleux E, Royston D, Rees G, Kesavan M, Hildyard C, Kazmi F, La Thangue N, Kerr D, Middleton MR, Collins GP. A Phase 2a cohort expansion study to assess the safety, tolerability, and preliminary efficacy of CXD101 in patients with advanced solid-organ cancer expressing HR23B or lymphoma. BMC Cancer. 2021 Jul 23;21(1):851. doi: 10.1186/s12885-021-08595-w.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CXD101 in people with Advanced Cancer, run by Oxford University Hospitals NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the maximum tolerated dose of CXD101 administered twice daily for 5 consecutive days every 21 days (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01977638, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2022.