DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial) - Master Screening Protocol

Launched by CANCER RESEARCH UK · Jan 31, 2023

Keywords

ClinConnect Summary

The DETERMINE trial is a research study looking at how existing cancer treatments can help patients with rare types of cancer or common cancers that have specific genetic changes. This trial is open to adults, teenagers, and children who have been diagnosed with a cancer that has a known mutation. To be eligible, participants must have tried standard treatments that did not work or have no available effective options, and their cancer must have progressed. The study aims to explore the benefits of targeted therapies for these patients, potentially leading to new treatment options in the future.

Participants in the trial will receive carefully monitored treatment based on their specific cancer type and genetic makeup. They will need to provide consent and may have to undergo additional tests like tissue biopsies or blood samples. The trial is currently recruiting participants, and those interested should discuss with their healthcare provider to see if they qualify. This study represents an opportunity to contribute to important research that may improve treatment options for patients with rare and challenging cancers.

Gender

ALL

Eligibility 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. Exceptional circumstances may apply as described in the protocol.
• • 3. and whose disease has progressed or is refractory.
• • 2. Diagnosis of a rare cancer harbouring an actionable genomic alteration, or common cancer types with rare actionable genomic alterations, that have been identified using a validated sequencing technique 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.
• • 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 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, 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 toxicity, 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.
• • 6. Radiotherapy (except for palliative reasons) or chemotherapy, endocrine therapy, nitrosoureas, mitomycin-C, immunotherapy and molecularly targeted agents or other investigational medicinal products 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 two weeks 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.