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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. Identifier: NCT00697879
Recruitment Status : Completed
First Posted : June 16, 2008
Last Update Posted : November 28, 2011
Information provided by (Responsible Party):
Chroma Therapeutics

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

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: CHR-3996 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study to Evaluate the Safety and Tolerability of the Histone Deacetylase Inhibitor, CHR-3996, in Patients With Advanced Solid Tumours
Study Start Date : February 2008
Actual Primary Completion Date : November 2010
Actual Study Completion Date : November 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Safety

Arm Intervention/treatment
Experimental: 1
Oral, once daily administration of CHR-3996 to determine safety and tolerability
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

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. To determine pharmacokinetic parameters of CHR-3996 [ Time Frame: After 1 and 28 days treatment ]
  2. To perform a preliminary assessment of the anti-tumour activity of CHR-3996 [ Time Frame: During treatment ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  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)


  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00697879

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Erasmus MC University Medical Center - Location Centrum
Rotterdam, Netherlands, 3015 CE
Erasmus University Medical Center - Location Daniel den Hoed
Rotterdam, Netherlands, 3075 EA
United Kingdom
The Royal Marsden Hospital
Sutton, Surrey, United Kingdom, SM2 5PT
Sponsors and Collaborators
Chroma Therapeutics
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Principal Investigator: F ALM Eskens, Dr Erasmus MC University Medical Center
Principal Investigator: Udai Banerji, Dr The Royal Marsden Hospital
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Responsible Party: Chroma Therapeutics Identifier: NCT00697879    
Other Study ID Numbers: CHR-3996-001
EudraCT Number: 2007-005043-19
First Posted: June 16, 2008    Key Record Dates
Last Update Posted: November 28, 2011
Last Verified: November 2011
Keywords provided by Chroma Therapeutics:
Solid tumour
histone deacetylase inhibitor
dose escalation
Additional relevant MeSH terms:
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Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action