A Study of Selective HDAC6 Inhibition With KA2507 in Advanced Biliary Tract Cancer

NCT04186156 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: ABC-11
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the preliminary efficacy of KA2507 (an orally active potent and selective HDAC6 inhibitor) in patients with advanced biliary tract cancer (BTC) previously treated with standard of care chemotherapy.

Conditions

Biliary Tract Cancer

Outcome Measures

Primary Outcomes (1)

• Proportion of patients alive and progression free at 4 months

  Proportion of patients alive and progression free at 4 months (objective disease progression as per RECIST 1.1)

  26 months

Secondary Outcomes (5)

• To evaluate tumour response to KA2507 (response rates and duration of response)

  26 months

• To evaluate overall survival

  26 months

• To characterise the safety and tolerability profile of KA2507

  26 months

• To characterise the pharmacokinetic profile of KA2507 in a subset of patients

  26 months

• To determine the pharmacodynamic response to KA2507

  26 months

Study Arms (1)

KA2507 (HDAC6 inhibitor)

EXPERIMENTAL

This is a single arm dose escalating study. Patients will be treated with open label KA2507 (HDAC6 inhibitor) capsules.

Drug: KA2507

Interventions

KA2507 DRUG

KA2507, an orally-active new chemical entity, is a potent and selective inhibitor of the HDAC6 enzyme, with potential clinical utility in the treatment of melanoma and other solid tumors. KA2507 has been shown to display potent in vitro activity in a range of cancer cell lines, including melanoma cell lines. KA2507 exerts potent in vivo efficacy in a syngeneic model of B16 melanoma. Here, the combination of the agent's direct tumor growth inhibition and metastasis suppression, coupled with its immunotherapeutic activity - demonstrated by decreased expression of STAT-3 and PD-L1 and increased expression of acetylated tubulin, gp100 and MHC Class I in tumors - have been observed.

Also known as: HDAC6 Inhibitor, HDAC6i

KA2507 (HDAC6 inhibitor)

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Signed informed consent
• Histological or cytological diagnosis of advanced (i.e. metastatic disease, or irresectable locally advanced, or recurrent) biliary tract cancer (to include intra or extra hepatic and gall bladder; ampullary cancer will not be included).
• Patient must have disease amenable to biopsy at baseline and consent to pre-treatment biopsy
• Clear evidence of disease progression following standard of care first line therapy with at least 1 measurable lesion using CT/MRI as defined by RECIST 1.1, OR clear evidence of disease progression based on the emergence of non-measurable disease (e.g. new cytologically confirmed ascites, pleural or pericardial effusion)
• Previous treatment with any line of chemotherapy for advanced disease (e.g. currently gemcitabine/cisplatin) OR radiotherapy
• ECOG performance status grade 0-1
• Adequate biliary drainage, with no evidence of ongoing infection
• Estimated life expectancy \> 3 months
• Patients intolerant of first-line standard of care chemotherapy will also be eligible provided there is evidence of disease progression

You may not qualify if:

• Unresolved or unstable serious toxic side-effects of prior chemotherapy or radiotherapy, i.e. ≥ grade 2 per CTCAE (common terminology criteria for adverse events, v5.0) except fatigue, alopecia and infertility
• Clinical evidence of cerebral metastases
• History of previous malignancy that could interfere with response evaluation
• Concurrent treatment with other investigational drugs within 4 weeks of initiating treatment
• Inadequate renal, liver, or haematological function defined as any of:
• eGFR \< 45 ml/min/1.73 m2 using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula
• ALT and/or AST \> 5 x ULN
• Neutropenia (absolute neutrophil count \< 1.5 x 109/L)
• Platelets \<100 x 109/L
• Haemoglobin ≤ 9 g/dL). NB the use of transfusion to achieve desired Hb is acceptable
• Total bilirubin ≥ 1.5 x ULN (except for patients with known Gilbert's syndrome)
• Known haemoglobinopathy due to HbS or HbC disease, α or β thalassemia, or Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Concomitant use of dapsone
• Untreated severe hypothyroidism
• Significant heart disease defined as any of the following:

Sponsors & Collaborators

• Karus Therapeutics Limited: lead
• University College, London: collaborator

Study Sites (1)

Cancer Research UK and UCL Cancer Trials Centre

London, W1T 4TJ, United Kingdom

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Study Officials

• John Bridgewater

  Cancer Research UK & UCL Cancer Trials Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: December 4, 2019
• Study Start: March 5, 2020
• Primary Completion: March 1, 2023
• Study Completion: October 1, 2023
• Last Updated: February 3, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)