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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Chroma Therapeutics
ClinicalTrials.gov Identifier:
NCT00697879
First received: June 10, 2008
Last updated: November 25, 2011
Last verified: November 2011
  Purpose

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 Intervention Phase
Solid Tumor
Drug: CHR-3996
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Chroma Therapeutics:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine pharmacokinetic parameters of CHR-3996 [ Time Frame: After 1 and 28 days treatment ] [ Designated as safety issue: Yes ]
  • To perform a preliminary assessment of the anti-tumour activity of CHR-3996 [ Time Frame: During treatment ] [ Designated as safety issue: Yes ]

Enrollment: 40
Study Start Date: February 2008
Study Completion Date: November 2011
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00697879

Locations
Netherlands
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
Investigators
Principal Investigator: F ALM Eskens, Dr Erasmus MC University Medical Center
Principal Investigator: Udai Banerji, Dr The Royal Marsden Hospital
  More Information

No publications provided

Responsible Party: Chroma Therapeutics
ClinicalTrials.gov Identifier: NCT00697879     History of Changes
Other Study ID Numbers: CHR-3996-001, EudraCT Number: 2007-005043-19
Study First Received: June 10, 2008
Last Updated: November 25, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Chroma Therapeutics:
tumour
Solid tumour
histone deacetylase inhibitor
dose escalation
cancer

Additional relevant MeSH terms:
Neoplasms
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014