NCT01977638

Brief 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. Patients with solid tumours, lymphoma and myeloma can be considered for this study.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
51

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Feb 2014

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 5, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 7, 2013

Completed
3 months until next milestone

Study Start

First participant enrolled

February 14, 2014

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 8, 2019

Completed
3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 14, 2022

Completed
Last Updated

October 18, 2022

Status Verified

October 1, 2021

Enrollment Period

5.6 years

First QC Date

November 5, 2013

Last Update Submit

October 17, 2022

Conditions

Advanced Cancer

Keywords

Advanced solid tumoursLymphomaMyeloma

Outcome Measures

Primary Outcomes (1)

  • To determine the maximum tolerated dose of CXD101 administered twice daily for 5 consecutive days every 21 days

    18 months

Secondary Outcomes (4)

  • To determine the pharmacokinetic (PK) profile of CXD101 following single and multiple dosing

    18 months

  • To enable a preliminary assessment of the anti-tumour activity of CXD101

    24 months

  • To evaluate the tissue expression of the biomarker HR23B

    24 months

  • To assess the pharmacodynamic effect of CXD101

    24 months

Study Arms (1)

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).

Drug: CXD101

Interventions

CXD101DRUG

Capsules, administered orally

Also known as: AZD9468
CXD101

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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.

You may not qualify if:

  • 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.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Oxford University Hospitals NHS Trust

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

Related Publications (1)

  • 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.

    PMID: 34301221DERIVED

MeSH Terms

Conditions

LymphomaNeoplasms, Plasma Cell

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 5, 2013

First Posted

November 7, 2013

Study Start

February 14, 2014

Primary Completion

October 8, 2019

Study Completion

October 14, 2022

Last Updated

October 18, 2022

Record last verified: 2021-10

Data Sharing

IPD Sharing
Will not share

Locations

GB(1)