DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial) - Master Screening Protocol
DETERMINE
2 other identifiers
interventional
825
1 country
27
Brief Summary
DETERMINE is an open-label phase II/III trial. It will look at targeted treatments in rare cancers or common cancers with rare genetic change (mutation). Patients must have a cancer with an identified mutation. This could be found during routine testing or as part of another research programme. The DETERMINE trial will recruit adults, teenagers and children. If a drug is found to benefit a new patient group, the study team will work with the NHS and the Cancer Drugs Funds to see if these drugs can be available for patients in the future. This clinicaltrials.gov record refers to the Overall Trial Protocol (Master Screening Record), additional records will be added to clinicaltrials.gov for each treatment arm.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Mar 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
February 10, 2023
CompletedStudy Start
First participant enrolled
March 1, 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
6.6 years
November 24, 2022
November 19, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of patients who consent to each arm.
This is a master screening entry with sub-study entries to capture the results of each arm. As such a primary outcome measure for this entry is not relevant, however this entry will be used to report the number of patients with a cancer containing the appropriate genetic alteration that have been successfully allocated and consented to each arm.
Up to 5 years.
Study Arms (6)
Treatment Arm 1: Alectinib
EXPERIMENTALThis alectinib treatment arm is for adult, paediatric and TYA patients with ALK-positive cancers.
Treatment Arm 2: Atezolizumab
EXPERIMENTALThis atezolizumab treatment arm is for adult, paediatric and TYA patients with cancers with high tumour mutational burden (TMB) or microsatellite instability high (MSI-high) or proven (previously diagnosed) constitutional mismatch repair deficiency (CMMRD).
Treatment Arm 3: Entrectinib
EXPERIMENTALThis entrectinib treatment arm is for adult, paediatric and TYA patients with ROS1 gene fusion-positive cancers.
Treatment Arm 4: Trastuzumab in combination with pertuzumab
EXPERIMENTALThis trastuzumab and pertuzumab treatment arm is for adult, paediatric and TYA patients with cancers with HER2 amplification or activating mutations.
Treatment Arm 5: Vemurafenib in combination with cobimetinib
EXPERIMENTALThis vemurafenib and cobimetinib treatment arm is for BRAF V600 mutation-positive cancers occurring in adults only.
Treatment Arm 6: Capmatinib
EXPERIMENTALThis capmatinib treatment arm is for adult patients with cancers harbouring MET dysregulations.
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.
Adult patients will receive 1200 mg of atezolizumab intravenously every 21 days. Paediatric patients will receive atezolizumab at a dose of 15 mg/kg (maximum 1200 mg) every 21 days. Patients may continue on treatment until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.
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 a dose adjusted for BSA. 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.
The initial loading dose of trastuzumab is 8 mg/kg body weight followed thereafter by a maintenance dose of 6 mg/kg body weight administered intravenously every 21 days. The initial loading dose of pertuzumab is 840 mg followed thereafter by a maintenance dose of 420 mg administered intravenously every 21 days. Paediatric patients will receive a dose of pertuzumab adjusted by body weight. Patients may continue until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.
Patients will receive vemurafenib at a dose of 960 mg (four tablets of 240 mg) orally on a twice daily schedule throughout a 28-day cycle. Patients will receive cobimetinib at a dose of 60 mg (three tablets of 20 mg) to be taken orally, once daily for 21 consecutive days (days 1 to 21 in each 28-day cycle); followed by a 7-day break. Patients may continue on treatment until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.
Patients will be administered capmatinib orally at a daily dose of 800 mg consisting of 400 mg (two 200 mg tablets) 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 qualify if:
- Any patient (adult patients or children and TYA as defined in each treatment arm appendix) with histologically proven locally advanced or metastatic cancer (solid tumour or haematological malignancy) who has:
- exhausted (or declined) standard-of-care treatment options.
- or for whom no effective standard treatment is available.
- and whose disease has progressed or is refractory. Exceptional circumstances may apply as described in the protocol.
- Diagnosis of a rare cancer harbouring an actionable genomic alteration, or common cancer types with rare actionable genomic alterations, that has been identified using a validated next-generation sequencing method and for which there is a relevant open treatment arm within the DETERMINE trial.
- Life expectancy of at least three months.
- Patients are able to provide written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up. For patients under 16 years old, the parent or legal guardian will be asked to provide written informed consent and the patient will be asked to provide age-appropriate assent (written or verbal, commensurate with age and level of understanding).
- Patients with objectively evaluable or measurable disease, according to an assessment method appropriate for their cancer type.
- Patients must provide a fresh tissue biopsy at baseline and blood samples for translational research. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow and/or trephine or lymph node biopsy samples may be taken.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (ECOG performance status 2 may be considered on an individual basis) (adults), Karnofsky score ≥50% (TYA) or Lansky Play scales ≥50% (\<12 years). Please see specific treatment arm appendices for any variations on this criterion and for definitions of adult and paediatric populations. Note: Paediatric patients: patients with Central Nervous System (CNS) tumours and a stable neurological deficit may be eligible with a performance status below 50%, at the discretion of the Investigator. In such cases, the deficit must be stable for at least 7 days prior to trial enrolment and be assessed by the local investigator as due to tumour or due to a post-surgical AE.
- 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 the birth control methods and duration of use of those methods, as specified in each treatment arm appendix.
- Male patients with partners of childbearing potential are eligible provided that they agree to the birth control methods and duration of use of those methods, as specified in each treatment arm appendix.
You may not qualify if:
- Ongoing AEs Common Terminology Criteria of Adverse Events (CTCAE) Grade ≥2 attributable to previous anti-cancer treatments. Exceptions to this are any clinically stable AEs, which in the opinion of the Investigator should not exclude the patient.
- At high medical risk, in the opinion of the Investigator, because of non-malignant systemic disease (including active uncontrolled infection).
- Female patients who are pregnant, breastfeeding or planning to become pregnant or male patients with a partner who is a woman of childbearing potential and is planning to become pregnant during the trial or following the last dose of IMP, as specified in each treatment arm appendix.
- Is (or plans to be) a patient in another interventional clinical trial, whilst taking part in this trial. Participation in an observational trial which does not involve administration of an Investigational Medicinal Product (IMP) and which, in the opinion of the local Investigator, would not place an unacceptable burden on the patient would be acceptable e.g. sample collection\* or QoL studies.
- \*for paediatric patients participating in other studies involving tissue/circulating tumour (ct) DNA/other blood collection, consideration would need to be given to the total blood volumes collected (as per the European Medicines Agency blood volume limits for children).
- Co-administration of anti-cancer therapies other than those administered in this trial (with the exception of lifelong hormone suppression such as luteinising hormone agonists/analogues in prostate cancer).
- Radiotherapy (except for palliative reasons) or chemotherapy, endocrine therapy (except when given for conditions other than malignant disease; e.g. thyroid replacement for hypothyroidism, hydrocortisone for cortisol deficiency/panhypopituitarism), nitrosoureas, mitomycin-C, immunotherapy and molecularly targeted agents or other IMPs within 4 weeks or 5 half-lives (whichever is the shorter).
- Rapidly progressing or symptomatically deteriorating brain metastases. Patients with previously treated brain metastases are eligible, provided the patient has not experienced a seizure or had a clinically significant change in neurological status within the 14 days (for adult patients) or 7 days (for paediatric patients) prior to the start of IMP administration. Such patients must be non-dependent on steroids or on a stable or reducing dose of steroid treatment for at least 14 days (or 7 days for paediatric patients) prior to the start of IMP administration. Primary brain or CNS malignancies are allowed providing the patient is clinically stable (if requiring corticosteroids must be at stable or decreasing doses for at least 14 days for adults and 7 days for paediatric patients prior to the start of IMP administration). Patients who have received brain irradiation must have completed whole-brain radiotherapy and/or stereotactic radiosurgery at least 14 days prior to the start of IMP administration.
- Any other condition which, in the opinion of the local Investigator, would not be in the best interests of the patient.
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
- Novartis Pharmaceuticalscollaborator
Study Sites (27)
Belfast City Hospital
Belfast, BT9 7AB, United Kingdom
University Hospital Birmingham
Birmingham, B15 2TT, United Kingdom
Birmingham Children's Hospital
Birmingham, B4 6NH, 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
- Overview of the DETERMINE trial.
- ClinicalTrials.gov record for DETERMINE Trial Treatment Arm 01 (alectinib) (NCT05770037)
- ClinicalTrials.gov record for DETERMINE Trial Treatment Arm 02 (atezolizumab) (NCT05770102)
- ClinicalTrials.gov record for DETERMINE Trial Treatment Arm 03 (entrectinib) (NCT05770544)
- ClinicalTrials.gov record for DETERMINE Trial Treatment Arm 04 (trastuzumab in combination with pertuzumab) (NCT05786716)
- ClinicalTrials.gov record for DETERMINE Trial Treatment Arm 05 (vemurafenib in combination with cobimetinib) (NCT05768178)
- ClinicalTrials.gov record for DETERMINE Trial Treatment Arm 06 (capmatinib) (NCT06988475)
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention 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
February 10, 2023
Study Start
March 1, 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 made within 5 years from last patient last visit for each of the treatment arms will be considered (refer to individual treatment arm records); 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.