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

NCT02759601 | Unknown Phase 1 DMC

• 2 other identifiers: 008260QM2012-000326-22
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Hepatocellular Carcinoma

Keywords

HDAC Inhibitor; Tefinostat; Inflammation; Hepatocellular Carcinoma; Cancer associated Inflammation in Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Determine Maximum Tolerated Dose

  Determining the maximal dose at either once or twice daily dosing at which no more than one patient (out of 3) at that dose level experiences a DLT.

  For 28 days following commencing IMP treatment. (Phase I)

Secondary Outcomes (2)

• Response Assessment

  From registration to disease progression.

• Phase I & II: To determine pharmacokinetic parameters for tefinostat and CHR-2847 when administered orally at different dose levels and dose schedules.

  Phase I: End of 28 day treatment period; Phase II: End of 84 days period

Other Outcomes (6)

• Phase I & II: To assess responses to target inhibition by tefinostat.

  Phase I: End of 28 day treatment period; Phase II: End of 84 days period

• Phase I & II: The impact of HDACi on circulating cytokine profiles.

  Phase I: End of 28 day treatment period; Phase II: End of 84 days period

• Phase I & II: To explore the feasibility of measuring tefinostat levels in tumour tissue.

  Phase I: End of 28 day treatment period; Phase II: End of 84 days period

Study Arms (1)

Tefinostat

OTHER

This is an open label, dose escalating, phase I/II study of Tefinostat administered orally, once or twice daily in 28 day cycles of treatment in patients with advanced hepatocellular carcinoma. Up to 5 cohorts of 3-6 patients (number is dependent on DLT occurrence) will be treated for 28 days once or twice daily (360, 480mg once daily, then 240, 360, 480mg twice daily) to determine safety and tolerability of Tefinostat and to identify the recommended dose for Phase II.

Drug: Tefinostat

Interventions

Tefinostat DRUG

Tefinostat is a novel type of HDACi used in cancer targeted specifically to cell of monocyte - macrophase lineage

Tefinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed, informed consent.
• 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.
• Patient is not a transplant candidate.
• Hepatitis is controlled by antiviral therapy (PEG-IFN, ribavirin, telaprevir, etc). Prophylactic Lamivudine for HBV carriers.
• Child-Pugh classification A or B7.
• 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.
• Age ≥ 18 years.
• Performance status (PS) 0-2 (ECOG scale).

You may not qualify if:

• Anti-cancer therapy including chemotherapy, radiotherapy, TACE, endocrine therapy, immunotherapy or use of other investigational agents within the 4 weeks prior to trial.
• Use of medicines known to prolong QTc within 14 days prior to the first dose of study drug (see Appendix III).
• Candidate for surgical resection, orthotopic liver transplantation, or loco-regional therapy such as radio-frequency ablation or chemoembolization.
• History of organ allograft.
• Co-existing active infection or serious concurrent illness.
• 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).
• 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.
• Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies.
• Gastrointestinal disorders that may interfere with absorption of the study drug.

Sponsors & Collaborators

• Queen Mary University of London: lead
• Chroma Therapeutics: collaborator

Study Sites (4)

Barts Health NHS Trust

London, Greater London, EC1M 7BE, United Kingdom

Location

Beatson Cancer Centre

Glasgow, United Kingdom

Location

Clatterbridge Cancer Centre

Liverpool, United Kingdom

Location

University College London Hospital

London, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Inflammation

Interventions

CHR 2845

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• David Propper

  Barts NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2014
• First Posted: May 3, 2016
• Study Start: January 1, 2013
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: December 20, 2018

Record last verified: 2018-12

Locations

GB (4)