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Safety Study of the Histone Deacetylase Inhibitor, CHR-3996, in Patients With Advanced Solid Tumours

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00697879
Recruitment Status : Completed
First Posted : June 16, 2008
Last Update Posted : November 28, 2011
Sponsor:
Information provided by (Responsible Party):
Chroma Therapeutics

Tracking Information
First Submitted Date  ICMJE June 10, 2008
First Posted Date  ICMJE June 16, 2008
Last Update Posted Date November 28, 2011
Study Start Date  ICMJE February 2008
Actual Primary Completion Date November 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 13, 2008)
To determine the safety, tolerability, dose-limiting toxicities (DLT), maximum acceptable dose (MAD) and maximum tolerated dose (MTD) of CHR-3996 when administered orally to patients with advanced or treatment refractory solid tumours [ Time Frame: After 28 days treatment ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2008)
  • To determine pharmacokinetic parameters of CHR-3996 [ Time Frame: After 1 and 28 days treatment ]
  • To perform a preliminary assessment of the anti-tumour activity of CHR-3996 [ Time Frame: During treatment ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of the Histone Deacetylase Inhibitor, CHR-3996, in Patients With Advanced Solid Tumours
Official Title  ICMJE A Phase I Study to Evaluate the Safety and Tolerability of the Histone Deacetylase Inhibitor, CHR-3996, in Patients With Advanced Solid Tumours
Brief Summary CHR-3996 is one of a new class of anti-cancer agents - histone deacetylase inhibitors (HDACi) - that has exhibited pleiotropic activity both in vitro and in vivo against a range of human cancer cells. Regulation of the acetylation of both histone and non-histone proteins by histone deacetylase enzymes is one of the key mechanisms involved in epigenetic control of gene expression. HDACi have demonstrated activity in both in vitro cytotoxicity, and in vivo tumour xenograft studies
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor
Intervention  ICMJE Drug: CHR-3996
Once daily oral ingestion of capsules (5, 10, 20 or 40 mg), dose depending on cohort, treatment cycle of 28 days
Other Names:
  • Histone deacetylase inhibitor
  • HDACi
Study Arms  ICMJE Experimental: 1
Oral, once daily administration of CHR-3996 to determine safety and tolerability
Intervention: Drug: CHR-3996
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 25, 2011)
40
Original Estimated Enrollment  ICMJE
 (submitted: June 13, 2008)
36
Actual Study Completion Date  ICMJE November 2011
Actual Primary Completion Date November 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

INCLUSION CRITERIA:

  1. Signed, informed consent
  2. Histologically or cytologically confirmed malignant solid tumour refractory to standard therapy or for which no standard therapy exists
  3. Recovered from all acute adverse effects of prior therapies (excluding alopecia and grade 1 neuropathy)
  4. Adequate bone marrow, hepatic and renal function including the following

    1. Hb ≥ 9.0 g/dL, absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥100 x 109/L
    2. Total bilirubin ≤ 1.5 x upper normal limit, excluding cases where elevated bilirubin can be attributed to Gilberts Syndrome
    3. AST (SGOT), ALT (SGPT) ≤ 2.5 x upper normal limit (or 5x UNL in the presence of liver metastases)
    4. Creatinine ≤ 1.5 x upper normal limit
  5. Age ≥ 18 years
  6. Performance status (PS) ≤ 2 (ECOG scale)
  7. Estimated life expectancy greater than 3 months
  8. Female patients with reproductive potential must have a negative serum pregnancy test within 7 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 3 months after discontinuation of treatment. Acceptable methods of contraception include IUD, oral contraceptive, subdermal implant and double barrier (condom with a contraceptive sponge)

EXCLUSION CRITERIA:

  1. Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the 4 weeks prior to trial entry (or a longer period depending on the defined characteristics of the agents used e.g. 6 weeks for mitomycin or nitrosourea, 3 months for antibodies). In patients with progressive disease, continuation of LHRH agonists for prostate cancer, bisphosphonates for bone disease and corticosteroids are permitted provided the dose does not change during the trial
  2. Patients with a prior allogeneic haematopoietic stem cell transplant
  3. Co-existing active infection or serious concurrent illness
  4. Patients with significant cardiovascular disease as defined by:

    1. history of congestive heart failure requiring therapy
    2. history of angina pectoris requiring treatment or myocardial infarction within 6 months prior to trial entry
    3. presence of severe valvular heart disease
    4. presence of an atrial or ventricular arrhythmia requiring treatment
    5. LVEF below the normal range at the study centre
    6. Uncontrolled hypertension
    7. A history of QTc abnormalities or with a mean QTc interval >450 msec at screening
  5. Any medical or other condition that in the investigator's opinion renders the patient unsuitable for this study due to unacceptable risk
  6. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies
  7. Gastrointestinal disorders that may interfere with absorption of the study drug.
  8. Patients with known brain tumours or metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  9. More than 6 prior chemotherapy regimens
  10. Patients requiring growth factor support (erythropoietin, G(M)CSF, etc)
  11. Patients requiring palliative radiotherapy within the last 4 weeks prior to study entry
  12. Uncontrolled hypercalcaemia (>CTCAE v3 grade I)
  13. Abnormal plasma potassium or magnesium levels (CTCAE v3 grade 3 or greater) despite therapy
  14. Pregnant or breast-feeding women
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00697879
Other Study ID Numbers  ICMJE CHR-3996-001
EudraCT Number: 2007-005043-19
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Chroma Therapeutics
Study Sponsor  ICMJE Chroma Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: F ALM Eskens, Dr Erasmus MC University Medical Center
Principal Investigator: Udai Banerji, Dr The Royal Marsden Hospital
PRS Account Chroma Therapeutics
Verification Date November 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP