Haematological MalignancyPhase 2/3DETERMINENCT05722886
DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial) - Master Screening Protocol
A Phase 2/3 study testing Alectinib, Atezolizumab and Entrectinib in people with Haematological Malignancy and Solid Tumour, run by Cancer Research UK at 27 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Haematological Malignancy, Solid Tumour
- What is being tested?
- Alectinib, Atezolizumab and Entrectinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 825 participants
- Where
- 27 sitesUnited Kingdom
- Study dates
- 1 Mar 2023to Oct 2029
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA OUTLINED BELOW AND WITHIN THE SPECIFIC TREATMENT ARM APPENDIX TO WHICH THEY ARE ENROLLED.
Core Inclusion Criteria:
- 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, lymph node or lump biopsy samples may be taken. For patients with haematological malignancies, a skin punch biopsy may also 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.
Core exclusion criteria:
- 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.
Trial locations and contacts
27 sites in 1 country. Contact the study team or a site near you to ask about taking part.
27 sites in 1 country
United Kingdom27 sites, 27 recruiting
- Recruiting
Belfast City Hospital
Belfast, BT9 7AB
Vicky Coyle, Prof, V.Coyle@qub.ac.uk
Vicky Coyle, Prof
- Recruiting
University Hospital Birmingham
Birmingham, B15 2TT
Gary Middleton, Prof, 0121 371 3573, G.Middleton@bham.ac.uk
Gary Middleton, Prof
- Not yet recruiting
Birmingham Children's Hospital
Birmingham, B4 6NH
Gerard Millen, Dr, 07921843607, g.millen@nhs.net
Gerard Millen, Dr
- Recruiting
Bristol Royal Hospital for Children
Bristol, BS2 8BJ
Antony Ng, Dr, 0117 342 8044, Antony.Ng@uhbw.nhs.uk
Antony Ng, Dr
- Recruiting
Bristol Haematology and Oncology Centre
Bristol, BS2 8ED
Antony Ng, Dr, 0117 342 8044, Antony.Ng@uhbw.nhs.uk
Antony Ng, Dr
- Recruiting
Addenbrooke's Hospital
Cambridge, CB2 OQQ
Bristi Basu, Dr, 01223 596105, bb313@medschl.cam.ac.uk
Bristi Basu, Dr
- Recruiting
Velindre Cancer Centre
Cardiff, CF14 2TL
Robert Jones, Dr, 02920 615888 ext. 6327, Robert.Hugh.Jones@wales.nhs.uk
Robert Jones, Dr
- Recruiting
Cardiff Children's Hospital
Cardiff, CF14 4XW
Madeline Adams, Dr, 02921842285, madeline.adams@wales.nhs.uk
Madeline Adams, Dr
- Recruiting
Western General Hospital
Edinburgh, EH4 2XU
Stefan Symeonides, Dr
Stefan Symeonides, Dr
- Recruiting
The Beatson Hospital
Glasgow, G12 OYN
Patricia Roxburgh, Dr, 0141 301 7118, Patricia.Roxburgh@glasgow.ac.uk
Patricia Roxburgh, Dr
- Recruiting
Royal Hospital for Children Glasgow
Glasgow, G51 4TF
Milind Ronghe, Dr, 0141 452 6692, Milind.Ronghe@ggc.scot.nhs.uk
Milind Ronghe, Dr
- Recruiting
Leicester Royal Infirmary
Leicester, LE1 5WW
Harriet Walter, Dr, 01162587602, harriet.walter1@nhs.net
Harriet Walter, Dr
- Recruiting
Alder Hey Hospital
Liverpool, L14 5AB
Lisa Howell, Dr, 0151 293 3679, Lisa.Howell@alderhey.nhs.uk
Lisa Howell, Dr
- Recruiting
University College London Hospital
London, NW1 2BU
Martin Forster, Prof, 020 3447 5085, M.Forster@ucl.ac.uk
Martin Forster, Prof
- Recruiting
Guy's Hospital
London, SE1 9RT
James Spicer, 020 7188 4260, james.spicer@kcl.ac.uk
James Spicer, Dr
- Recruiting
Great Ormond Street Hospital
London, WC1N 3JH
Darren Hargrave, Dr, 0207 813 8525, Darren.hargrave@gosh.nhs.uk
Darren Hargrave, Dr
- Recruiting
Royal Manchester Children's Hospital
Manchester, M13 9WL
Guy Makin, Dr, 0161 701 8419, Guy.Makin@mft.nhs.uk
Guy Makin, Dr
- Recruiting
The Christie Hospital
Manchester, M20 4BX
Matthew Krebs, Dr, 0161 918 7672, matthew.krebs@nhs.net
Matthew Krebs
- Recruiting
Clatterbridge Cancer Centre
Metropolitan Borough of Wirral, CH63 4JY
Dan Palmer, Dr, 0151 706 4172 / 0151 706 4177, daniel.palmer@liverpool.ac.uk
Dan Palmer, Dr
- Recruiting
Great North Children's Hospital
Newcastle, NE1 4LP
Alastair Greystoke, Dr, 0191 2138476, Alastair.Greystoke@newcastle.ac.uk
Alastair Greystoke, Dr
- Recruiting
Freeman Hospital
Newcastle, NE7 7DN
Alastair Greystoke, Dr, 0191 2138476, Greystoke@newcastle.ac.uk
Alastair Greystoke, Dr
- Recruiting
Churchill Hospital
Oxford, OX3 7LE
Sarah Pratap, Dr, 01865 235273, Sarah.Pratap@ouh.nhs.uk
Sarah Pratap, Dr
- Recruiting
John Radcliffe Hospital
Oxford, OX3 9DU
Sarah Pratap, Dr, 01865 235273, Sarah.Pratap@ouh.nhs.uk
Sarah Pratap, Dr
- Recruiting
Weston Park Hospital
Sheffield, S10 2SJ
Sarah Danson, Dr, 0114 226 5068, s.danson@sheffield.ac.uk
Sarah Danson, Dr
- Recruiting
Sheffield's Children's Hospital
Sheffield, S10 2TH
Daniel Yeomanson, Dr, 01142717366, danyeomanson@nhs.net
Daniel Yeomanson, Dr
- Recruiting
Southampton General Hospital
Southampton, SO16 6YD
Juliet Gray, Prof, 0238 120 6639, Juliet.Gray@uhs.nhs.uk
Juliet Gray, Prof
- Recruiting
The Royal Marsden Hospital
Sutton, SM2 5PT
Lynley Marshall, Dr, 0208 661 3678, LynleyVanessa.Marshall@icr.ac.uk
Lynley Marshall, Dr
About this study
Official title: 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
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.
Read the detailed description
DETERMINE is an umbrella-basket platform trial to evaluate the efficacy of licensed targeted therapies in rare* adult, paediatric and teenage/young adult (TYA) cancers with actionable genomic alterations, including common cancers with rare actionable alterations.
*Rare is defined generally as incidence less than 6 cases in 100,000 patients (includes paediatric and TYA cancers) or common cancers with rare alterations.
The number of treatment arms opened will depend on the number of licensed medicines identified for inclusion. Each trial cohort 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.
This clinicaltrials.gov record refers to the Overall Trial Protocol (Master Screening Record), please refer to the references section for links to the individual treatment arm records.
The main aims of the clinical trial arms are:
- To describe the anti-cancer activity of licensed targeted drugs outside their licensed indication.
- To assess the safety and adverse event (AE) profile of licensed, targeted anti-cancer drugs in the target population.
- To understand biological mechanisms for response and resistance to targeted therapies.
- To evaluate the quality of life (QoL) of target populations receiving the licensed, targeted anti-cancer drugs.
This Master Screening Record will capture the number of patients with a cancer containing the appropriate genetic alteration that have been successfully allocated and consented to each arm. The trial results (according to the protocol defined outcome measures) will be reported per-arm for each treatment arm.
The ultimate aim is to translate positive clinical findings to the NHS to provide new treatment options for rare adult, paediatric and TYA cancers.
- Conditions
- Haematological Malignancy, Solid Tumour
- Being tested
- Alectinib, Atezolizumab, Entrectinib, Trastuzumab in combination with pertuzumab, Vemurafenib in combination with cobimetinib
- Keywords
- Adult, Alectinib, ALK Tyrosine Kinase Receptor, Antineoplastic Agents, Atezolizumab, BRAF Kinase, Cancer, Child, CMMRD, Cobimetinib, Entrectinib, Genes, HER2, Immune Checkpoint Inhibitors, Immunological, Lymphoproliferative Disorders, Malignancy, Malignant Neoplasms, MSI, Molecular Targeted Therapy, Mutation
- Medical subject headings
- Hematologic Neoplasms, Neoplasms, Lymphoproliferative Disorders, Neoplasms by Histologic Type, Neoplasms by Site
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlectinibDrug
Also called Alecensa
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.
AtezolizumabDrug
Also called Tecentriq
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.
EntrectinibDrug
Also called Rozlytrek
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.
Trastuzumab in combination with pertuzumabDrug
Also called Herceptin in combination with Perjeta
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.
Vemurafenib in combination with cobimetinibDrug
Also called Zelboraf in combination with Cotellic
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.
CapmatinibDrug
Also called Tabrecta
Patients will receive 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.
Dabrafenib in combination with trametinibDrug
Also called Tafinlar in combination with Mekinist, Finlee in combination with Spexotras
Adult patients (≥18 years) will receive dabrafenib at a dose of 150 mg (two 75 mg tablets) twice daily (total daily dose 300 mg). Paediatric patients (1 to <12 years) will receive dabrafenib dose adjusted by body weight as 10 mg dispersible tablets orally twice daily. Paediatric patients (≥12 years) and TYA patients (16 to <18 years) will have the option to receive adult or paediatric dosing. Adult patients will receive trametinib at a daily dose of 2 mg (one 2 mg tablet) orally once daily (total daily dose 2 mg). Paediatric patients receive trametinib at a dose adjusted by body weight as 0.05 mg/m^2 powder for oral solution twice daily. Paediatric patients (≥12 years) and TYA patients (16 to <18 years) will have the option to receive adult or paediatric dosing. Each cycle of treatment will consist of 28 days. Patients may continue until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm 1: Alectinib | Experimental | This alectinib treatment arm is for adult, paediatric and TYA patients with ALK-positive cancers. Receives: Drug: Alectinib |
| Treatment Arm 2: Atezolizumab | Experimental | This 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). Receives: Drug: Atezolizumab |
| Treatment Arm 3: Entrectinib | Experimental | This entrectinib treatment arm is for adult, paediatric and TYA patients with ROS1 gene fusion-positive cancers. Receives: Drug: Entrectinib |
| Treatment Arm 4: Trastuzumab in combination with pertuzumab | Experimental | This trastuzumab and pertuzumab treatment arm is for adult, paediatric and TYA patients with cancers with HER2 amplification or activating mutations. Receives: Drug: Trastuzumab in combination with pertuzumab |
| Treatment Arm 5: Vemurafenib in combination with cobimetinib | Experimental | This vemurafenib and cobimetinib treatment arm is for BRAF V600 mutation-positive cancers occurring in adults only. Receives: Drug: Vemurafenib in combination with cobimetinib |
| Treatment Arm 6: Capmatinib | Experimental | This capmatinib treatment arm is for adult patients with cancers harbouring MET dysregulations. Receives: Drug: Capmatinib |
| Treatment Arm 7: Dabrafenib in combination with trametinib | Experimental | This dabrafenib and trametinib treatment arm is for adult, paediatric and TYA patients with cancers harbouring BRAF V600 mutations. Receives: Drug: Dabrafenib in combination with trametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2023
- Study start1 Mar 2023
- Primary completionOct 2029 (estimated)
- Study completionOct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Haematological MalignancyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 825 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cancer Research UK
- Sponsor type
- University, hospital or other
- Collaborators
- University of Manchester, University of Birmingham, Royal Marsden NHS Foundation Trust, Hoffmann-La Roche, Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Matthew Krebs, Dr, Principal investigator, The Christie Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05722886
- Sponsor's protocol ID
- CRUKD/21/004
- Other IDs
- IRAS ID: 1004057
- Acronym
- DETERMINE
- Status last verified
- Jun 2026
- First submitted
- 24 Nov 2022
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05722886
- Acronym / sponsor ID
- DETERMINE / CRUKD/21/004
- Conditions
- Haematological Malignancy, Solid Tumour
- Keywords
- Adult, Alectinib, ALK Tyrosine Kinase Receptor, Antineoplastic Agents, Atezolizumab, BRAF Kinase, Cancer, Child
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 825 participants (estimated)
- Lead sponsor
- Cancer Research UKUniversity, hospital or other
- Collaborators
- University of Manchester, University of Birmingham, Royal Marsden NHS Foundation Trust, Hoffmann-La Roche, Novartis Pharmaceuticals
- Study start
- 1 Mar 2023 (actual)
- Primary completion
- Oct 2029 (estimated)
- Study completion
- Oct 2029 (estimated)
- First posted
- 10 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
DETERMINE is an umbrella-basket platform trial to evaluate the efficacy of licensed targeted therapies in rare* adult, paediatric and teenage/young adult (TYA) cancers with actionable genomic alterations, including common cancers with rare actionable alterations.
*Rare is defined generally as incidence less than 6 cases in 100,000 patients (includes paediatric and TYA cancers) or common cancers with rare alterations.
The number of treatment arms opened will depend on the number of licensed medicines identified for inclusion. Each trial cohort 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.
This clinicaltrials.gov record refers to the Overall Trial Protocol (Master Screening Record), please refer to the references section for links to the individual treatment arm records.
The main aims of the clinical trial arms are:
- To describe the anti-cancer activity of licensed targeted drugs outside their licensed indication.
- To assess the safety and adverse event (AE) profile of licensed, targeted anti-cancer drugs in the target population.
- To understand biological mechanisms for response and resistance to targeted therapies.
- To evaluate the quality of life (QoL) of target populations receiving the licensed, targeted anti-cancer drugs.
This Master Screening Record will capture the number of patients with a cancer containing the appropriate genetic alteration that have been successfully allocated and consented to each arm. The trial results (according to the protocol defined outcome measures) will be reported per-arm for each treatment arm.
The ultimate aim is to translate positive clinical findings to the NHS to provide new treatment options for rare adult, paediatric and TYA cancers.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm 1: Alectinib | Experimental | Drug: AlectinibThis alectinib treatment arm is for adult, paediatric and TYA patients with ALK-positive cancers. |
| Treatment Arm 2: Atezolizumab | Experimental | Drug: AtezolizumabThis 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 | Experimental | Drug: EntrectinibThis entrectinib treatment arm is for adult, paediatric and TYA patients with ROS1 gene fusion-positive cancers. |
| Treatment Arm 4: Trastuzumab in combination with pertuzumab | Experimental | Drug: Trastuzumab in combination with pertuzumabThis 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 | Experimental | Drug: Vemurafenib in combination with cobimetinibThis vemurafenib and cobimetinib treatment arm is for BRAF V600 mutation-positive cancers occurring in adults only. |
| Treatment Arm 6: Capmatinib | Experimental | Drug: CapmatinibThis capmatinib treatment arm is for adult patients with cancers harbouring MET dysregulations. |
| Treatment Arm 7: Dabrafenib in combination with trametinib | Experimental | Drug: Dabrafenib in combination with trametinibThis dabrafenib and trametinib treatment arm is for adult, paediatric and TYA patients with cancers harbouring BRAF V600 mutations. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlectinibAlso: AlecensaAdult 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. | Drug | Treatment Arm 1: Alectinib |
| AtezolizumabAlso: TecentriqAdult 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. | Drug | Treatment Arm 2: Atezolizumab |
| EntrectinibAlso: RozlytrekAdult 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. | Drug | Treatment Arm 3: Entrectinib |
| Trastuzumab in combination with pertuzumabAlso: Herceptin in combination with PerjetaThe 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. | Drug | Treatment Arm 4: Trastuzumab in combination with pertuzumab |
| Vemurafenib in combination with cobimetinibAlso: Zelboraf in combination with CotellicPatients 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. | Drug | Treatment Arm 5: Vemurafenib in combination with cobimetinib |
| CapmatinibAlso: TabrectaPatients will receive 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. | Drug | Treatment Arm 6: Capmatinib |
| Dabrafenib in combination with trametinibAlso: Tafinlar in combination with Mekinist, Finlee in combination with SpexotrasAdult patients (≥18 years) will receive dabrafenib at a dose of 150 mg (two 75 mg tablets) twice daily (total daily dose 300 mg). Paediatric patients (1 to <12 years) will receive dabrafenib dose adjusted by body weight as 10 mg dispersible tablets orally twice daily. Paediatric patients (≥12 years) and TYA patients (16 to <18 years) will have the option to receive adult or paediatric dosing. Adult patients will receive trametinib at a daily dose of 2 mg (one 2 mg tablet) orally once daily (total daily dose 2 mg). Paediatric patients receive trametinib at a dose adjusted by body weight as 0.05 mg/m^2 powder for oral solution twice daily. Paediatric patients (≥12 years) and TYA patients (16 to <18 years) will have the option to receive adult or paediatric dosing. Each cycle of treatment will consist of 28 days. Patients may continue until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent. | Drug | Treatment Arm 7: Dabrafenib in combination with trametinib |
Primary outcome
Number of patients who consent to each arm.
Time frame: Up to 5 years.
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
- Overview of the DETERMINE trial.Link provided by the sponsor.
- ClinicalTrials.gov record for DETERMINE Trial Treatment Arm 01 (alectinib) (NCT05770037)Link provided by the sponsor.
- ClinicalTrials.gov record for DETERMINE Trial Treatment Arm 02 (atezolizumab) (NCT05770102)Link provided by the sponsor.
- ClinicalTrials.gov record for DETERMINE Trial Treatment Arm 03 (entrectinib) (NCT05770544)Link provided by the sponsor.
- ClinicalTrials.gov record for DETERMINE Trial Treatment Arm 04 (trastuzumab in combination with pertuzumab) (NCT05786716)Link provided by the sponsor.
- ClinicalTrials.gov record for DETERMINE Trial Treatment Arm 05 (vemurafenib in combination with cobimetinib) (NCT05768178)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Matthew Krebs, Dr principal investigator
The Christie Hospital
27 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Alectinib, Atezolizumab and Entrectinib in people with Haematological Malignancy and Solid Tumour, run by Cancer Research UK at 27 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Aida Sarmiento Castro (+44 207 242 0200, determine@cancer.org.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients who consent to each arm. (time frame: Up to 5 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Jul 2026.