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A Phase I Study to Evaluate the Safety and Tolerability of the Histone Deacetylase Inhibitor, CHR-3996, in Patients With Advanced Solid Tumours

Phase 1
18 Years
Not Enrolling
Solid Tumor

Thank you

Trial Information

A Phase I Study to Evaluate the Safety and Tolerability of the Histone Deacetylase Inhibitor, CHR-3996, in Patients With Advanced Solid Tumours

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)


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

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

12. Uncontrolled hypercalcaemia (>CTCAE v3 grade I)

13. Abnormal plasma potassium or magnesium levels (CTCAE v3 grade 3 or greater) despite

14. Pregnant or breast-feeding women

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

After 28 days treatment

Safety Issue:


Principal Investigator

F ALM Eskens, Dr

Investigator Role:

Principal Investigator

Investigator Affiliation:

Erasmus MC University Medical Center


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

February 2008

Completion Date:

November 2011

Related Keywords:

  • Solid Tumor
  • tumour
  • Solid tumour
  • histone deacetylase inhibitor
  • dose escalation
  • cancer
  • Neoplasms