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Evaluating existing drugs for rare cancers with specific genetic changes

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

Phase2; Phase3 Interventional Cancer Research UK · NCT05722886

This study is testing if approved cancer drugs can help people with rare cancers or common cancers that have specific genetic changes feel better and live longer.

Quick facts

PhasePhase2; Phase3
Study typeInterventional
Enrollment825 (estimated)
SexAll
SponsorCancer Research UK Academic / other
Drugs / interventionschemotherapy, immunotherapy
Locations27 sites (Belfast and 26 other locations)
Trial IDNCT05722886 on ClinicalTrials.gov

What this trial studies

DETERMINE is an open-label phase II/III trial designed to assess the effectiveness of licensed targeted therapies in treating rare cancers or common cancers with rare genetic mutations. The trial will recruit patients of all ages who have a cancer with an identified mutation, which may be discovered through routine testing or other research programs. Each treatment arm will focus on a specific drug, and the study aims to evaluate the anti-cancer activity, safety, and quality of life for patients receiving these therapies. If successful, the findings could lead to broader access to these drugs for patients in the future.

Who should consider this trial

Good fit: Ideal candidates include adults, teenagers, and children with locally advanced or metastatic cancers that have specific actionable genomic alterations.

Not a fit: Patients with cancers that do not have identified actionable mutations or those who have not exhausted standard treatment options may not benefit from this trial.

Why it matters

Potential benefit: If successful, this trial could provide new treatment options for patients with rare cancers that currently have limited effective therapies.

How similar studies have performed: Other studies have shown promise in using targeted therapies for rare cancers, indicating that this approach has potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA OUTLINED BELOW AND WITHIN THE SPECIFIC TREATMENT ARM APPENDIX TO WHICH THEY ARE ENROLLED.

Core Inclusion Criteria:

1. 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:

   1. exhausted (or declined) standard-of-care treatment options.
   2. or for whom no effective standard treatment is available.
   3. and whose disease has progressed or is refractory. Exceptional circumstances may apply as described in the protocol.
2. 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.
3. Life expectancy of at least three months.
4. 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).
5. Patients with objectively evaluable or measurable disease, according to an assessment method appropriate for their cancer type.
6. 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.
7. 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.
8. 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.
9. 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:

1. 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.
2. At high medical risk, in the opinion of the Investigator, because of non-malignant systemic disease (including active uncontrolled infection).
3. 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.
4. 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).
5. 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).
6. 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).
7. 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.
8. Any other condition which, in the opinion of the local Investigator, would not be in the best interests of the patient.

Where this trial is running

Belfast and 26 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
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Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.