DETERMINE Trial Treatment Arm 01: Alectinib in Adult, Paediatric and Teenage/Young Adult Patients With ALK Positive Cancers
DETERMINE
DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial): An Umbrella-Basket Platform Trial to Evaluate the Efficacy of Targeted Therapies in Rare Adult, Paediatric and Teenage/Young Adult (TYA) Cancers With Actionable Genomic Alterations, Including Common Cancers With Rare Actionable Alterations. Treatment Arm 01: Alectinib in Adult, Paediatric and Teenage/Young Adult Patients With ALK Positive Cancers
2 other identifiers
interventional
30
1 country
27
Brief Summary
This clinical trial is looking at a drug called alectinib. Alectinib is approved as standard of care treatment for adult patients with certain types of lung cancer. This means it has gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Alectinib works in lung cancer patients with a particular mutation in their cancer known as ALK. Investigators now wish to find out if it will be useful in treating patients with other cancer types which have the same mutation. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Dec 2023
Longer than P75 for phase_2
27 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 24, 2022
CompletedFirst Posted
Study publicly available on registry
March 15, 2023
CompletedStudy Start
First participant enrolled
December 18, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2029
November 24, 2025
November 1, 2025
5.8 years
November 24, 2022
November 19, 2025
Conditions
Keywords
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 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 (12)
Duration of response (DR)
Disease assessment performed every 2 cycles of alectinib (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 alectinib for up to 2 years.
Best percentage change in sum of target lesion / index lesion diameters (PCSD)
Disease assessment performed every 2 cycles of alectinib (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 alectinib for up to 2 years.
Time to treatment discontinuation (TTD)
From first dose of alectinib to discontinuation of trial treatment up to 5 years with an average calculated and presented with results entry.
Progression-Free Survival time (PFS)
Disease assessment performed every 2 cycles of alectinib (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 alectinib for up to 2 years.
Time to Progression (TTP)
Disease assessment performed every 2 cycles of alectinib (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 alectinib for up to 2 years.
- +7 more secondary outcomes
Other Outcomes (1)
EORTC-QLQ-C30-Standardised Area Under Summary Score Curve (QLQSAUC) in adult patients.
QoL surveys performed prior to inclusion, every cycle (each cycle is 28 days) and at EoT visit (up to 5 years).
Study Arms (1)
Treatment Arm 01: Alectinib
EXPERIMENTALThis alectinib treatment arm is for adult, paediatric and teenage/young adult (TYA) patients with ALK-positive cancers.
Interventions
Adult patients will be administered alectinib orally at a dose of 600 mg (four 150 mg capsules) twice daily. Paediatric patients with a body weight ≥40 kg and who are able to swallow the capsules, will be administered alectinib orally at a dose of 600 mg (four 150 mg capsules) twice daily. Each cycle of treatment will consist of 28 days and patients may continue on treatment until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.
Eligibility Criteria
You may not qualify if:
- A. Confirmed diagnosis of an ALK-positive malignancy using an analytically validated next-generation sequencing method.
- B. Women of childbearing potential are eligible, provided that they meet the following criteria:
- Have a negative serum or urine pregnancy test before enrolment and;
- Agree to use one form of highly effective birth control method such as:
- I. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation \[oral, intravaginal or transdermal\]
- II. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable)
- III. intrauterine device (IUD)
- IV. intrauterine hormone-releasing system (IUS)
- V. bilateral tubal occlusion
- VI. vasectomised partner
- VII. sexual abstinence
- Effective from the first administration of alectinib, throughout the trial and for three months after the last administration of alectinib.
- C. Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from first administration of alectinib, throughout the trial and for three months after the last administration of alectinib:
- Agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or 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 criterion B, above.
- +27 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Cancer Research UKlead
- University of Manchestercollaborator
- University of Birminghamcollaborator
- Royal Marsden NHS Foundation Trustcollaborator
- Hoffmann-La Rochecollaborator
Study Sites (27)
Belfast City Hospital
Belfast, BT9 7AB, United Kingdom
University Hospital Birmingham
Birmingham, B15 2TT, United Kingdom
Birmingham Children's Hospital
Birmingham, United Kingdom
Bristol Royal Hospital for Children
Bristol, BS2 8BJ, United Kingdom
Bristol Haematology and Oncology Centre
Bristol, BS2 8ED, United Kingdom
Addenbrooke's Hospital
Cambridge, CB2 OQQ, United Kingdom
Velindre Cancer Centre
Cardiff, CF14 2TL, United Kingdom
Cardiff Children's Hospital
Cardiff, CF14 4XW, United Kingdom
Western General Hospital
Edinburgh, EH4 2XU, United Kingdom
The Beatson Hospital
Glasgow, G12 OYN, United Kingdom
Royal Hospital for Children Glasgow
Glasgow, G51 4TF, United Kingdom
Leicester Royal Infirmary
Leicester, LE1 5WW, United Kingdom
Alder Hey Hospital
Liverpool, L14 5AB, United Kingdom
University College London Hospital
London, NW1 2BU, United Kingdom
Guy's Hospital
London, SE1 9RT, United Kingdom
Great Ormond Street Hospital
London, WC1N 3JH, United Kingdom
Royal Manchester Children's Hospital
Manchester, M13 9WL, United Kingdom
The Christie Hospital
Manchester, M20 4BX, United Kingdom
Clatterbridge Cancer Centre
Metropolitan Borough of Wirral, CH63 4JY, United Kingdom
Great North Children's Hospital
Newcastle, NE1 4LP, United Kingdom
Freeman Hospital
Newcastle, NE7 7DN, United Kingdom
Churchill Hospital
Oxford, OX3 7LE, United Kingdom
John Radcliffe Hospital
Oxford, OX3 9DU, United Kingdom
Weston Park Hospital
Sheffield, S10 2SJ, United Kingdom
Sheffield's Children's Hospital
Sheffield, S10 2TH, United Kingdom
Southampton General Hospital
Southampton, SO16 6YD, United Kingdom
The Royal Marsden Hospital
Sutton, SM2 5PT, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Matthew Krebs, Dr
The Christie Hospital
Central Study Contacts
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
November 24, 2022
First Posted
March 15, 2023
Study Start
December 18, 2023
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 alectinib 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
Individual de-identified patient data will be shared with researchers whose proposed use of the data is approved by a review committee of the Sponsor.