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

NCT05770544 | Recruiting Phase 2

• 2 other identifiers: CRUKD/21/004 - Treatment Arm 3IRAS ID: 1004057
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 27

Brief Summary

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.

Conditions

Haematological Malignancy; Malignancy; Malignant Neoplasm; Lymphoproliferative Disorders; Neoplasms by Histologic Type; Neoplasms by Site; Cancer; Brain Neoplasms; Melanoma; Glioma; Solid Tumour

Keywords

Adult; Antineoplastic Agents; Cancer; Child; Entrectinib; Malignancy; Malignant Neoplasms; Molecular Targeted Therapy; Mutation; Neoplasms by Histologic Site; Neoplasms by Site; Oncogene; Paediatric; Protein Kinase Inhibitors; Rare; ROS1 Protein, human; Tumour-agnostic; Young adult

Outcome Measures

Primary Outcomes (2)

• Objective Response (OR)

  An OR is defined as the confirmed occurrence of either a Complete Response (CR) or Partial Response (PR) according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 criteria (or immune related \[ir\]-RECIST or standard imaging criteria for specific disease e.g. Response Evaluation in Neuro Oncology criteria \[RANO\]). In patients with leukaemia, OR will be defined as the occurrence of CR, CRi (CR with incomplete neutrophil recovery) or CRp (CR with incomplete platelet recovery). The trial will report the proportion of patients with an OR and 95% credible interval.

  Disease assessments to be performed up to 24 weeks from the start of trial treatment.

• Durable Clinical Benefit (DCB)

  DCB is defined as the absence of disease progression for at least 24 weeks from the start of trial treatment according to RECIST Version 1.1 criteria (or ir-RECIST or standard imaging criteria for specific disease e.g. RANO criteria) and, where relevant (e.g. for haematological malignancies), by standard bone marrow response assessment criteria. Alternative definitions of DCB based on different time points may be pre-specified for particular sub-cohorts if 24 weeks is not clinically relevant. The trial will report the proportion of patients with a DCB and 95% credible interval.

  Disease assessments to be performed up to 24 weeks from the start of trial treatment.

Secondary Outcomes (13)

• Duration of response (DR)

  Disease assessment every 2 cycles of entrectinib (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose of entrectinib for up to 2 years.

• Best percentage change in sum of target lesion / index lesion diameters (PCSD)

  Disease assessment every 2 cycles of entrectinib (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose of entrectinib for up to 2 years.

• Time to treatment discontinuation (TTD)

  From first dose of entrectinib to discontinuation of trial treatment up to 5 years.

• Progression-Free Survival time (PFS)

  Disease assessment every 2 cycles of entrectinib (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose of entrectinib for up to 2 years.

• Time to Progression (TTP)

  Disease assessment every 2 cycles of entrectinib (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose of entrectinib for up to 2 years.

Study Arms (1)

Treatment Arm 03

EXPERIMENTAL

This entrectinib treatment arm is for adult, paediatric and TYA patients with ROS1 gene fusion-positive malignancies.

Drug: Entrectinib

Interventions

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). Paediatric patients with BSA \<1.51 m\^2 will receive entrectinib at a dose of 100 mg (BSA=0.43-0.50 m\^2) or 200 mg (BSA=0.51-0.80 m\^2) or 300 mg (BSA=0.81-1.10 m\^2) or 400 mg (BSA=1.11-1.50 m\^2). Each cycle of treatment will consist of 28 days and patients may continue until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.

Also known as: Rozlytrek

Treatment Arm 03

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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

Sponsors & Collaborators

• Cancer Research UK: lead
• University of Manchester: collaborator
• University of Birmingham: collaborator
• Royal Marsden NHS Foundation Trust: collaborator
• Hoffmann-La Roche: collaborator

Study Sites (27)

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

RECRUITING

University Hospital Birmingham

Birmingham, B15 2TT, United Kingdom

RECRUITING

Birmingham Children's Hospital

Birmingham, United Kingdom

NOT YET RECRUITING

Bristol Royal Hospital for Children

Bristol, BS2 8BJ, United Kingdom

RECRUITING

Bristol Haematology and Oncology Centre

Bristol, BS2 8ED, United Kingdom

RECRUITING

Addenbrooke's Hospital

Cambridge, CB2 OQQ, United Kingdom

RECRUITING

Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

RECRUITING

Cardiff Children's Hospital

Cardiff, CF14 4XW, United Kingdom

NOT YET RECRUITING

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

RECRUITING

The Beatson Hospital

Glasgow, G12 OYN, United Kingdom

RECRUITING

Royal Hospital for Children Glasgow

Glasgow, G51 4TF, United Kingdom

RECRUITING

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

RECRUITING

Alder Hey Hospital

Liverpool, L14 5AB, United Kingdom

RECRUITING

University College London Hospital

London, NW1 2BU, United Kingdom

RECRUITING

Guy's Hospital

London, SE1 9RT, United Kingdom

RECRUITING

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

RECRUITING

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

NOT YET RECRUITING

The Christie Hospital

Manchester, M20 4BX, United Kingdom

RECRUITING

Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

RECRUITING

Great North Children's Hospital

Newcastle, NE1 4LP, United Kingdom

RECRUITING

Freeman Hospital

Newcastle, NE7 7DN, United Kingdom

RECRUITING

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

RECRUITING

John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

RECRUITING

Weston Park Hospital

Sheffield, S10 2SJ, United Kingdom

RECRUITING

Sheffield's Children's Hospital

Sheffield, S10 2TH, United Kingdom

RECRUITING

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

RECRUITING

The Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

RECRUITING

Related Links

• Overview of the DETERMINE trial
• ClinicalTrials.gov record for DETERMINE Trial Master Screening Protocol (NCT05722886).

MeSH Terms

Conditions

Hematologic Neoplasms; Neoplasms; Lymphoproliferative Disorders; Neoplasms by Histologic Type; Neoplasms by Site; Brain Neoplasms; Melanoma; Glioma

Interventions

entrectinib

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial

Study Officials

• Matthew Krebs, Dr

  The Christie Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aida Sarmiento Castro

CONTACT

+44 207 242 0200; determine@cancer.org.uk

Study Design

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

Study Record Dates

• First Submitted: February 22, 2023
• First Posted: March 15, 2023
• Study Start: November 30, 2025
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: November 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: All requests for data relating to this treatment arm that are made within 5 years from last patient last visit for the entrectinib treatment arm will be considered; requests made subsequently will be considered where possible.
• Access Criteria: When a request has been approved, Cancer Research UK will provide access to the de-identified individual patient-level data and appropriate supporting information. A signed Data Sharing Agreement must be in place before accessing requested information. Requests should be submitted to drugdev@cancer.org.uk.

Locations

GB (27)