AzTrials
AzTrials

Biliary Tract CancerPhase 2NCT04186156

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

A Phase 2 study testing KA2507 in people with Biliary Tract Cancer, run by Karus Therapeutics Limited at 1 site in United Kingdom.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Biliary Tract Cancer
What is being tested?
KA2507
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited Kingdom
Study dates
5 Mar 2020to Oct 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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

Who cannot join

  • 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
Show all 26Show fewer
  • 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:
  • NYHA grade 3 or 4 symptomatic heart failure
  • Unstable angina or acute myocardial infarction within 3 months
  • cardiac ventricular arrhythmia within 3 months that is not controlled by drug therapy and/or by cardiac ablation
  • QTcF > 470 ms on screening ECG or history of Torsades de pointes
  • Any other concurrent severe and/or uncontrolled medical or surgical condition which, in the view of the investigator, could compromise the patient's participation in the study
  • Patients with active hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
  • Active infection requiring antibiotics within two weeks prior to treatment
  • Males who are unable to or refuse to use barrier contraception during treatment and for 3 months after
  • Women who are pregnant, breast-feeding or either unable to or refuse to use effective means of contraception during treatment
  • Patients who are unable to swallow capsules and/or have a surgical or anatomical condition that precludes swallowing and absorbing oral medication on an ongoing basis
  • Any other condition that would, in the investigator's judgement, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Cancer Research UK and UCL Cancer Trials Centre

    London, W1T 4TJ

Other trials in United Kingdom

About this study

Official title: A Phase II Study of Selective HDAC6 Inhibition With KA2507 in Advanced Biliary Tract Cancer Previously Treated With Standard of Care Chemotherapy (ABC-11)

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.

Read the detailed description

To evaluate the 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.

ABC-11 is an open-label, multi-centre study of HDAC6 inhibition using KA2507 in patients with advanced biliary tract cancer previously treated with standard of care chemotherapy.

This is a single-arm single-stage phase II study designed using A'Hern's methodology.

The primary objective of this study is to assess the preliminary efficacy of KA2507 in patients with advanced BTC previously treated with standard of care chemotherapy

A fixed daily dose of KA2507 (800mg BID) will be administered to all patients based on a phase I study, KTP-003.

Being tested
KA2507
Medical subject headings
Biliary Tract Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KA2507Drug

    Also called HDAC6 Inhibitor, HDAC6i

    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.

Study groups in NCT04186156
Study groupRoleWhat they receive
KA2507 (HDAC6 inhibitor)ExperimentalThis is a single arm dose escalating study. Patients will be treated with open label KA2507 (HDAC6 inhibitor) capsules.
Receives: Drug: KA2507

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: 26 months

Secondary outcomes (5)

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

    To assess the effect of KA2507 on overall response rate according to RECIST Version 1.1.

    Measured: 26 months

  2. To evaluate overall survival

    Time to death after study treatment.

    Measured: 26 months

  3. To characterise the safety and tolerability profile of KA2507

    Incidence of adverse events (Common Terminology Criteria for Adverse Events [CTCAE] Version 5.0)

    Measured: 26 months

  4. To characterise the pharmacokinetic profile of KA2507 in a subset of patients

    KA2507 plasma pharmacokinetic parameters in plasma from up to six patients.

    Measured: 26 months

  5. To determine the pharmacodynamic response to KA2507

    Evidence of selective HDAC6 target engagement inferred through measurement of acetylated tubulin and acetylated histone in peripheral blood T cells from up to six patients

    Measured: 26 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Dec 2019
  2. Study start5 Mar 2020
  3. Primary completionMar 2023 (estimated)
  4. Study completionOct 2023 (estimated)

Why it stopped: Study not progressing

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04186156
Sponsor's protocol ID
ABC-11
Status last verified
Jan 2021
First submitted
17 Jul 2019
Last updated
3 Feb 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing KA2507 in people with Biliary Tract Cancer, run by Karus Therapeutics Limited at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 3 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of patients alive and progression free at 4 months (time frame: 26 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04186156.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in