Clinical Trials /

Phase 1 Trial of CXD101 in Patients With Advanced Cancer

NCT01977638

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.

Related Conditions:
  • Cancer
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

  • Advanced Cancer

Interventions

DrugSynonymsArms
CXD101AZD9468CXD101

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

NameTypeDescriptionInterventions
CXD101ExperimentalDose escalation study of CXD101 administered orally twice daily for 5 consecutive days in every 21 day cycle. Starting dose 1mg twice daily (2mg/day).
  • CXD101

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:Recruiting
Lead Sponsor:Oxford University Hospitals NHS Trust

Trial Keywords

  • Advanced solid tumours
  • Lymphoma
  • Myeloma

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