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Advanced Solid TumoursPhase 1NCT01585701

Phase I Study of AT13148, a Novel AGC Kinase Inhibitor

A Phase 1 study testing AT13148 in people with Advanced Solid Tumours, run by Cancer Research UK at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this first clinical study of the noval multiple AGC kinase inhibitor, AT13148, is to identify the recommended dose for future studies in cancer patients by exploring the safety and maximum tolerated dose and biological effects in patients with advanced solid tumours. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumours
What is being tested?
AT13148
How many people
56 participants
Where
1 siteUnited Kingdom
Study dates
May 2012to 10 Jan 2018
Phase
Phase 1
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

  • Histologically proven advanced solid tumours, refractory to conventional treatment, or for which no conventional therapy exists or is declined by the patient. Paraffin-embedded tumour tissue must be available for genetic mutation status testing.
  • Life expectancy of at least 12 weeks
  • World Health Organisation (WHO) performance status of 0, 1 or 2
  • Haematological and biochemical indices within the ranges shown below. These measurements must be performed within 7 days before their first dose of AT13148 taken between Day -7 to -4.
  • Laboratory Test Value required
  • Haemoglobin (Hb) ≥ 9.0 g/dL
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  • Absolute neutrophil count ≥ 1.5 x 10^9 /L
  • Platelet count ≥ 100 x 10^9/L
  • Fasting glucose ≤ 7 mmol/L
  • Either:
  • Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • Or:
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x (ULN) unless raised due to tumour in which case up to 5 x ULN is permissible
  • Either:
  • Calculated creatinine clearance ≥ 50 mL/min
  • Or:
  • Isotope clearance measurement ≥ 50mL/min (uncorrected)
  • Adequate lung function indicated by a resting oxygen saturation level (on air) ≥ 94%, a CO-transfer factor > 60%
  • 18 years or over
  • Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up

Who cannot join

  • Radiotherapy (except for palliative reasons), endocrine therapy (except luteinizing hormone releasing hormone (LHRH) agonists for prostate cancer), immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosoureas, Mitomycin-C) and 4 weeks for investigational medicinal products) before treatment.
  • Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the Drug Development Office (DDO) should not exclude the patient.
  • Symptomatic brain metastases (if present they must have been stable for > 3 months).
  • Ability to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have a intra-uterine device and condom, diaphragm with spermicidal gel and condom) during the study and for six months afterwards are considered eligible.
  • Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception [condom plus spermicide] during the study and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (e.g. condom plus spermicidal gel) to prevent exposure to the foetus or neonate.
  • Major thoracic or abdominal surgery from which the patient has not yet recovered.
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  • At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
  • Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).
  • History of auto-immune disease or known allergy to peanuts.
  • Concurrent hypotension defined as a baseline supine blood pressure (BP) systolic < 90 mmHg.
  • Patients receiving anti-hypertensive treatment or treatment with beta- blockers or rate-limiting calcium agents. A washout period of 5 x half- life of the drug should be applied following withdrawal of any of these treatments.
  • Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA]), prior history of cardiac ischaemia or prior history of cardiac arrhythmia. Coronary angioplasty or stenting in the previous 12 months.
  • Patients with a known left ventricular ejection fraction (LVEF) < 50%. A multi-gated acquisition (MUGA) scan or echocardiogram (ECHO) must be performed in all patients.
  • Concurrent diabetes requiring treatment (diet-controlled diabetes would be acceptable).
  • Prior bone marrow transplant or have had extensive radiotherapy to greater than 25% of bone marrow within eight weeks.
  • A history of or underlying interstitial lung disease.
  • Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical study.
  • Is a participant or plans to participate in another interventional clinical study whilst taking part in this study. Participation in an observational study would be acceptable.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Royal Marsden Hospital, Institute of Cancer Research

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

About this study

Official title: A Cancer Research UK Phase I First in Man Study of the Novel AGC Kinase Inhibitor AT13148 Given Orally in Patients With Advanced Solid Tumours.

The purpose of this first clinical study of the noval multiple AGC kinase inhibitor, AT13148, is to identify the recommended dose for future studies in cancer patients by exploring the safety and maximum tolerated dose and biological effects in patients with advanced solid tumours.

Read the detailed description

AT13148 is a new drug which looks promising in laboratory studies. We now wish to find out if it will be useful in treating patients with cancer. AT13148 is a type of drug called a protein kinase inhibitor. It blocks several different chemical messengers (enzymes) called AGC kinase proteins. These chemical messengers are part of the signaling process within cells which can make cells produce chemicals that trigger and control cell growth and cell death. In some types of cancer these chemical messengers are 'switched on' or 'switched off' permanently due to changes in the genes of cells called "gene mutations" leading to uncontrolled cancer cell growth. AT13148 targets multiple protein kinases from three families of kinases unlike many of the other protein kinase inhibitors currently being tested which target just one or two kinases. This may mean that it will work better and in a wider group of cancer patients. Patients will not be selected to take part based on having these gene mutations for this first trial because we want to learn more about which mutations are most important but this would be the hope for future trials. The patient population anticipated to benefit from this drug includes certain types of breast, prostate and ovarian cancer which more commonly have these gene mutations.

Being tested
AT13148
Keywords
Phase I, Oncology, AGC Kinase inhibitor, Protein Kinase inhibitor, Clinical Trial, Multiple protein kinases
Medical subject headings
Neoplasms

What participants receive

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

  • AT13148Biological

    Days 1, 3, 5 of a weekly schedule in dose escalation cohorts of three patients. Continuous dosing until progression or unacceptable toxicity develops up to a maximum of 12 cycles.

What is being measured

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

  1. Determining a dose at which no more than one patient out of up to six patients at the same dose level experience a highly probably or probably drug-related dose limiting toxicity (DLT).

  2. Determining causality of each adverse event Adverse Event to AT13148 and grading severity according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.02.

Secondary outcomes (2)

  1. Determining the correlation between pharmacokinetic studies and toxicity and/or efficacy.

  2. Any response (stable disease, partial response or complete response) in any of the patients as determined by the Response Evaluation Criteria in Solid Tumours RECIST) criteria version 1.1.criteria version 1.1.

Timeline

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

  1. First posted26 Apr 2012 (estimated)
  2. Study startMay 2012
  3. Primary completion10 Jan 2018
  4. Study completion10 Jan 2018

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01585701
Sponsor's protocol ID
CRUKD/12/001
Status last verified
Jul 2018
First submitted
25 Apr 2012
Last updated
20 Jul 2018
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AT13148 in people with Advanced Solid Tumours, run by Cancer Research UK 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 20 inclusion and 18 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: finished, as of the sponsor's last update on 20 Jul 2018. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Determining a dose at which no more than one patient out of up to six patients at the same dose level experience a highly probably or probably drug-related dose limiting toxicity (DLT).. The study lists 2 primary outcomes in all. 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 NCT01585701.

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 20 Jul 2018.

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