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

Phase 1 Trial of <span class="go-doc-concept go-doc-intervention">CXD101</span> in Patients With Advanced <span class="go-doc-concept go-doc-disease">Cancer</span>

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

    NCT ID: NCT01977638

    ORG ID: CXD101-0901

    NCI ID: 2009-012743-42

    Trial Conditions

    Advanced Cancer

    Trial Interventions

    Drug Synonyms Arms
    CXD101 AZD9468 CXD101

    Trial 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). 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

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

    Secondary Outcome Measures

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

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

    To evaluate the tissue expression of the biomarker HR23B

    To assess the pharmacodynamic effect of CXD101

    Trial Keywords

    Advanced solid tumours

    Lymphoma

    Myeloma