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Looking for participantsPhase2/Phase3

DETERMINE Trial Treatment Arm 03: Entrectinib in Adult, Paediatric and Teenage/Young Adult Patients With ROS1 Gene Fusion-Positive Cancers.

Sponsor: Cancer Research UK

NCT ID: NCT05770544

View on ClinicalTrials.gov ↗

At a glance

What the study gets you
Access to the study treatment being tested
Type of study
Interventional (receives a drug or procedure)
Time in hospital
In-person visits at study sites — visit count not specified by the sponsor
Drug or intervention
Entrectinib (drug)
How long the study runs
Study runs about 47 months (dates as stated)
About the drug or intervention
Entrectinib — drug: Adult and paediatric patients with body surface area (BSA) ≥1.51 m\^2 will receive entrectinib orally at a dose of 600 mg daily dose (three 200 mg capsules per day).
Patient visit burden
Not specified by the sponsor
Type of study
Testing a treatment
Ages
Not specified
Who
All
Number of participants
30
Started
2025-11-30
Last checked
2025-11

Plain English Summary

What is this study?

  • • Testing a new treatment for haematological malignancy
  • • Phase2/Phase3 - 30 participants
  • • This clinical trial is looking at a drug called entrectinib

Who can take part?

  • • Adults
  • • Diagnosed with haematological malignancy

Where?

  • • Belfast - Belfast City Hospital
  • • Birmingham - University Hospital Birmingham
  • • Birmingham - Birmingham Children's Hospital
  • • Bristol - Bristol Royal Hospital for Children
  • • +23 more UK sites

This is a simplified summary. Always discuss with your doctor before making any decisions.

About This Trial

This clinical trial is looking at a drug called entrectinib. Entrectinib is approved as standard of care treatment for adult patients with non-small cell lung cancer (NSCLC) which have a particular molecular alteration called ROS1-positive, and patients 12 years old or above with solid tumours which have another type of change in the cancer cells. This means it has gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Investigators now wish to find out if it will be useful in treating patients with other cancer types which have the same molecular alteration (ROS1-positive). If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future. This trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.

More detail

DETERMINE Treatment Arm 03 (entrectinib) aims to evaluate the efficacy of entrectinib in ROS1 gene fusion-positive rare\* adult, paediatric and teenage/young adult (TYA) cancers and in common cancers where a ROS1 mutation or amplification is considered to be infrequent. \*Rare is defined generally as incidence less than 6 cases in 100,000 patients (includes paediatric and teenagers/young adult cancers) or common cancers with rare alterations. This treatment arm has a target sample size of 30 evaluable patients. Sub-cohorts may be defined and further expanded to a target of 30 evaluable patients each. The ultimate aim is to translate positive clinical findings to the NHS (Cancer Drugs Fund) to provide new treatment options for rare adult, paediatric and TYA cancers. OUTLINE: Pre-screening: The Molecular Tumour Board makes a treatment recommendation for the patient based on molecularly-defined cohorts. Screening: Consenting patients undergo biopsy and collection of blood samples for research purposes. Treatment: Patients will receive entrectinib until disease progression without clinical benefit, unacceptable adverse events (AEs) or withdrawal of consent. Patients will also undergo collection of blood samples at various intervals while receiving treatment and at the end of treatment visit (EoT). After completion of study treatment, patients are followed up every 3 months for 2 years THE DETERMINE TRIAL MASTER (SCREENING) PROTOCOL: Please see DETERMINE Trial Master (Screening) Protocol record (NCT05722886) for information on the DETERMINE Trial Master Protocol and applicable documents.

Haematological MalignancyMalignancyMalignant NeoplasmLymphoproliferative DisordersNeoplasms by Histologic TypeNeoplasms by SiteCancerBrain NeoplasmsMelanomaGliomaSolid Tumour

How this trial compares with your answers

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What we know so far

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Preliminary match based on your answers. Full eligibility requires on-site assessment including medical history, physical exam, and lab tests. This does not guarantee enrolment.

Eligibility at a Glance

Key info

  • Age: Not specified
  • Who can join: All genders

Biomarkers mentioned

ROS1gene fusionHave a negativeROS1 fusionmettesting positiveCD4

What the study is looking for

  • ✓A. Confirmed diagnosis of a ROS1 gene fusion-positive cancer, other than NSCLC, that has been identified using...
  • ✓C. Patients with a BSA of 0.43m\^2 and over.
  • ✓F. Women of childbearing potential are eligible provided that they meet the following criteria:
  • ✓Have a negative serum or urine pregnancy test before enrolment and either:
  • ✓Agree to use one form of highly effective birth control method such as:

Who cannot take part

  • ✗A. Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or within five...
  • ✗B. Diagnosis of ROS1 fusion-positive NSCLC
  • ✗C. Prior treatment with the same class of drug unless genetic profile demonstrates a mechanism of resistance known...
  • ✗D. Patients with significant cardiovascular disease are excluded as defined by:
  • ✗i. Current congestive heart failure requiring therapy (New York Heart Association III or IV) or known left...
See the full criteria
THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA WITHIN THE DETERMINE MASTER PROTOCOL (NCT05722886) AND WITHIN THE TREATMENT ARM 03 (ENTRECTINIB) OUTLINED BELOW\* \*When entrectinib-specific inclusion/exclusion criteria or precautions below differ from those specified in the Master Protocol, the entrectinib-specific criteria will take precedence. Inclusion Criteria: A. Confirmed diagnosis of a ROS1 gene fusion-positive malignancy, other than NSCLC, that has been identified using an analytically validated next-generation sequencing method. B. Patients must be able and willing to undergo a fresh tissue biopsy at baseline and blood samples for translational research. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow aspiration and/or trephine or lymph node biopsy samples may be taken. C. Patients with a BSA of 0.43m\^2 and over. D. ADULT PATIENTS (≥18 years): Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility. E. PAEDIATRIC PATIENTS (\<18 years): Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility. F. Women of childbearing potential are eligible provided that they meet the following criteria: * Have a negative serum or urine pregnancy test before enrolment and either: * Agree to use one form of highly effective birth control method such as: I. Oral, intravaginal or transdermal combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation II. Oral, injectable or implantable progestogen-only hormonal contraception associated with inhibition of ovulation III. Intrauterine device (IUD) IV. Intrauterine hormone-releasing system (IUS) V. Bilateral tubal occlusion VI. Vasectomised partner Plus a barrier method if using a hormonal method: male or female condom with or without spermicide; cap, diaphragm or sponge with spermicide OR • Sexual abstinence; Effective from the first administration of entrectinib, throughout the trial and for five weeks after the last administration of entrectinib. G. Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from the first administration of entrectinib, throughout the trial and for three months after the last administration of entrectinib: * Agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or to sexual abstinence. * Non-vasectomised male patients with partners who are women of childbearing potential must also be willing to ensure that their partner uses a highly effective method of contraception as in F above. * Male patients with pregnant or lactating partners must be advised to use barrier method contraception (e.g. condom) to prevent drug exposure of the foetus or neonate. All male patients must refrain from donating sperm for the same period. Exclusion Criteria: A. Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or within five weeks following their last dose of entrectinib B. Diagnosis of ROS1 fusion-positive NSCLC C. Prior treatment with the same class of drug unless genetic profile demonstrates a mechanism of resistance known to be potentially sensitive to entrectinib D. Patients with significant cardiovascular disease are excluded as defined by: i. Current congestive heart failure requiring therapy (New York Heart Association III or IV) or known left ventricular ejection fraction (LVEF) \<50% (moderate to severe). ii. History of unstable angina pectoris or myocardial infarction up to three months prior to trial entry, or current poorly controlled angina (symptoms weekly or more). iii. Presence of symptomatic or severe valvular heart disease (severe by local echo graphic criteria or American Heart Association/American Cardiac College Stage C or D). iv. History of a clinically significant cardiac arrhythmia up to three months prior to trial entry (asymptomatic atrial fibrillation or asymptomatic first-degree heart block are permitted. v. History of stroke (ischaemic or haemorrhagic) within the last three months. • Patients with primary CNS tumours may be considered unless intra-tumoural bleeding has occurred within 2 weeks of the first dose of entrectinib, and patients with punctate CNS haemorrhages \<3 mm may be considered. E. Patients with a baseline QTcF (Corrected QT interval by Fridericia formula) interval longer than 450 milliseconds (ms) for male patients and 470 ms for female patients, patients with congenital long QTcF syndrome, and patients taking medicinal products that are known to prolong the QTc interval. F. History of additional risk factors for Torsades de Pointes (e.g., family history of long QT syndrome) G. Grade ≥2 peripheral neuropathy H. Known active infections (bacterial, fungal or viral) that would interfere with the assessment of safety or efficacy of entrectinib, including human immunodeficiency virus (HIV) positivity. Patients with history of testing positive for HIV infection are eligible provided the each of the following conditions are met: * CD4 count ≥350/μL; * undetectable viral load; * receiving antiretroviral therapy (ART) that does not interact with IMP (patients should be on established ART for at least four weeks); and * no HIV/ acquired immune deficiency syndrome (AIDS)-associated opportunistic infection in the last 12 months. I. Known hypersensitivity to entrectinib or any of the excipients J. Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment, or anticipation of need for such a vaccine during entrectinib treatment or within six months after the final dose of entrectinib K. Patient unable to swallow entrectinib intact, without chewing, crushing or opening the capsules (as per the dosing schedule and suitable dosing strengths available). Any active gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would reasonably affect drug absorption L. Patients with personal history of significant osteopenia (screening for osteopenia not required) M. Any clinically significant concomitant disease or condition (or its treatment) that could interfere with the conduct of the trial or absorption of oral medications that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this trial

Where Is This Study? (27 UK sites)

Belfast City Hospital

Belfast BT9 7AB, United Kingdom

Recruiting
Site contact (verified)
Vicky Coyle, ProfPrincipal Investigator
Vicky Coyle, ProfV.Coyle@qub.ac.uk

University Hospital Birmingham

Birmingham B15 2TT, United Kingdom

Recruiting
Site contact (verified)
Gary Middleton, ProfPrincipal Investigator

Birmingham Children's Hospital

Birmingham, United Kingdom

NOT_YET_RECRUITING
Site contact (verified)
Gerard Millen, DrPrincipal Investigator

Bristol Royal Hospital for Children

Bristol BS2 8BJ, United Kingdom

Recruiting
Site contact (verified)
Antony Ng, DrPrincipal Investigator

Bristol Haematology and Oncology Centre

Bristol BS2 8ED, United Kingdom

Recruiting
Site contact (verified)
Antony Ng, DrPrincipal Investigator

Addenbrooke's Hospital

Cambridge CB2 OQQ, United Kingdom

Recruiting
Site contact (verified)
Bristi Basu, DrPrincipal Investigator

Velindre Cancer Centre

Cardiff CF14 2TL, United Kingdom

Recruiting
Site contact (verified)
Robert Jones, DrPrincipal Investigator

Cardiff Children's Hospital

Cardiff CF14 4XW, United Kingdom

NOT_YET_RECRUITING
Site contact (verified)
Madeline Adams, DrPrincipal Investigator

Western General Hospital

Edinburgh EH4 2XU, United Kingdom

Recruiting
Site contact (verified)
Stefan Symeonides, DrPrincipal Investigator

The Beatson Hospital

Glasgow G12 OYN, United Kingdom

Recruiting
Site contact (verified)
Patricia Roxburgh, DrPrincipal Investigator

Royal Hospital for Children Glasgow

Glasgow G51 4TF, United Kingdom

Recruiting
Site contact (verified)
Milind Ronghe, DrPrincipal Investigator

Leicester Royal Infirmary

Leicester LE1 5WW, United Kingdom

Recruiting
Site contact (verified)
Olubukola Ayodele, DrPrincipal Investigator

Alder Hey Hospital

Liverpool L14 5AB, United Kingdom

Recruiting
Site contact (verified)
Lisa Howell, DrPrincipal Investigator

University College London Hospital

London NW1 2BU, United Kingdom

Recruiting
Site contact (verified)
Martin Forster, ProfPrincipal Investigator

Guy's Hospital

London SE1 9RT, United Kingdom

Recruiting
Site contact (verified)
James Spicer, DrPrincipal Investigator

Great Ormond Street Hospital

London WC1N 3JH, United Kingdom

Recruiting
Site contact (verified)
Darren Hargrave, DrPrincipal Investigator

Royal Manchester Children's Hospital

Manchester M13 9WL, United Kingdom

NOT_YET_RECRUITING
Site contact (verified)
Guy Makin, DrPrincipal Investigator

The Christie Hospital

Manchester M20 4BX, United Kingdom

Recruiting
Site contact (verified)
Matthew Krebs, DrPrincipal Investigator

Clatterbridge Cancer Centre

Metropolitan Borough of Wirral CH63 4JY, United Kingdom

Recruiting
Site contact (verified)
Dan Palmer, DrPrincipal Investigator

Great North Children's Hospital

Newcastle NE1 4LP, United Kingdom

Recruiting
Site contact (verified)
Alastair Greystoke, DrPrincipal Investigator

Freeman Hospital

Newcastle NE7 7DN, United Kingdom

Recruiting
Site contact (verified)
Alastair Greystoke, DrPrincipal Investigator

Churchill Hospital

Oxford OX3 7LE, United Kingdom

Recruiting
Site contact (verified)
Sarah Pratap, DrPrincipal Investigator

John Radcliffe Hospital

Oxford OX3 9DU, United Kingdom

Recruiting
Site contact (verified)
Sarah Pratap, DrPrincipal Investigator

Weston Park Hospital

Sheffield S10 2SJ, United Kingdom

Recruiting
Site contact (verified)
Sarah Danson, DrPrincipal Investigator

Sheffield's Children's Hospital

Sheffield S10 2TH, United Kingdom

Recruiting
Site contact (verified)
Daniel Yeomanson, DrPrincipal Investigator

Southampton General Hospital

Southampton SO16 6YD, United Kingdom

Recruiting
Site contact (verified)
Juliet Gray, ProfPrincipal Investigator

The Royal Marsden Hospital

Sutton SM2 5PT, United Kingdom

Recruiting
Site contact (verified)
Lynley Marshall, DrPrincipal Investigator

How to Get in Touch

Aida Sarmiento Castro

Sponsor contact

CONTACT

+44 207 242 0200 determine@cancer.org.uk
Data sourced from ClinicalTrials.gov · Last verified: 2025-11