Dose Escalation Trial of Tefinostat for Cancer Associated Inflamation in Hepatocellular Carcinoma (HCC)

• Status: Unknown status
• Trial end date: 2018-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is being carried out to assess the best dose of a new drug, called tefinostat, in treating liver cancer.

Tefinostat is a new drug that blocks enzymes called histone deacetylases (pronounced dee-as-et-isle-azes). Cells need these enzymes to grow and divide. Blocking them may stop cancer growing. Drugs that block these enzymes are called histone deacetylase inhibitors or 'HDAC inhibitors'.

Tefinostat has never been given to patients with liver cancer before so it isn't known which dose is best at treating liver cancer. To find this out the study will be testing one dose and if that is safe, then test a higher dose and so on.

The aim of this study is to find the best dose of tefinostat without causing side effects. The study will be looking closely at any side effects patients might experience from this treatment.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Queen Mary University of London
• Collaborator: Chroma Therapeutics
• Treatments: Histone Deacetylase Inhibitors

Criteria

Inclusion Criteria:

1. Signed, informed consent.

2. Histologically or cytologically confirmed malignant HCC refractory to standard therapy or for which no standard therapy exists.

a. Patients with alcoholic cirrhosis may be included dependent on clinical judgement as to their ability to conform to the protocol.

3. Patient is not a transplant candidate.

4. Hepatitis is controlled by antiviral therapy (PEG-IFN, ribavirin, telaprevir, etc). Prophylactic Lamivudine for HBV carriers.

5. Child-Pugh classification A or B7.

6. Adequate bone marrow, hepatic and renal function including the following:

• Hb ≥ 9.0g/dL, absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥75 x 109/L.

• Total bilirubin ≤ 1.5 x upper normal limit, excluding cases where elevated bilirubin can be attributed to Gilberts Syndrome.

• AST (SGOT), ALT (SGPT) ≤ baseline + 4 x upper normal limit .

• Creatinine ≤ 1.5 x upper normal limit.

• Serum albumin > 28g/L.

• INR < 1.5 or a Pt/PTT within normal limits.

7. Age ≥ 18 years.

8. Performance status (PS) 0-2 (ECOG scale).

9. Estimated life expectancy greater than 3 months.

10. 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 or contraceptive pessary).

Exclusion Criteria:

1. Anti-cancer therapy including chemotherapy, radiotherapy, TACE, endocrine therapy, immunotherapy or use of other investigational agents within the 4 weeks prior to trial.

2. Use of medicines known to prolong QTc within 14 days prior to the first dose of study drug (see Appendix III).

3. Candidate for surgical resection, orthotopic liver transplantation, or loco-regional therapy such as radio-frequency ablation or chemoembolization.

4. History of organ allograft.

5. Co-existing active infection or serious concurrent illness.

6. Significant cardiovascular disease as defined by:

• History of congestive heart failure requiring therapy.

• History of unstable angina pectoris or myocardial infarction up to 6 months prior to trial entry.

• Presence of severe valvular heart disease.

• Presence of a ventricular arrhythmia requiring treatment.

• LVEF < 50% (or less than institutional norm- some places have 45%).

• QTc interval ≥ 450ms for men and ≥ 470ms for women (using Bazett's formula).

7. Any co-existing medical condition that in the Investigator's judgement will substantially increase the risk associated with the patient's participation in the study.

8. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies.

9. Gastrointestinal disorders that may interfere with absorption of the study drug.

10. Patients requiring palliative radiotherapy within the last 4 weeks of study entry.

11. Uncontrolled hypercalcaemia (>CTCAE v4.03 grade I).

12. Pregnant or breast-feeding women.

13. Patients who have received an investigational drug within the last 4 weeks.