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.
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.
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.
Single group
Alectinib
DrugAdult 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.
Atezolizumab
DrugAdult 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.
Entrectinib
DrugAdult 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 pertuzumab
DrugThe 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 cobimetinib
DrugPatients 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.
Capmatinib
DrugPatients 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 trametinib
DrugAdult 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.
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Treatment groupsSee each treatment group below.
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.
Click on the lead sponsor to view all of their trials.
Cancer Research UK
Lead sponsor
University of Manchester
Collaborator
University of Birmingham
Collaborator
Royal Marsden NHS Foundation Trust
Collaborator
Hoffmann-La Roche
Collaborator
Novartis Pharmaceuticals
Collaborator
