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

Sponsor
Cancer Research UK
Study ID
NCT05722886
Phase
PHASE2/PHASE3
Status
Recruiting
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Conditions

  • Haematological Malignancy
  • Solid Tumour

Eligibility Criteria

Sex
ALL
Age
N/A - N/A
Healthy Volunteers
Not accepted

Interventions

  • Alectinib — DRUG
    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.
  • Atezolizumab — DRUG
    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.
  • Entrectinib — DRUG
    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 pertuzumab — DRUG
    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 cobimetinib — DRUG
    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.
  • Capmatinib — DRUG
    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.

Study Details

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.

Key Dates

Start date
Mar 1, 2023
Status verified
Nov 2025
Primary completion
Oct 31, 2029
Completion
Oct 31, 2029

Study Design

Enrollment
825 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Treatment Arm 1: Alectinib
    This alectinib treatment arm is for adult, paediatric and TYA patients with ALK-positive cancers.
  • Experimental: Treatment Arm 2: Atezolizumab
    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).
  • Experimental: Treatment Arm 3: Entrectinib
    This entrectinib treatment arm is for adult, paediatric and TYA patients with ROS1 gene fusion-positive cancers.
  • Experimental: Treatment Arm 4: Trastuzumab in combination with pertuzumab
    This trastuzumab and pertuzumab treatment arm is for adult, paediatric and TYA patients with cancers with HER2 amplification or activating mutations.
  • Experimental: Treatment Arm 5: Vemurafenib in combination with cobimetinib
    This vemurafenib and cobimetinib treatment arm is for BRAF V600 mutation-positive cancers occurring in adults only.
  • Experimental: Treatment Arm 6: Capmatinib
    This capmatinib treatment arm is for adult patients with cancers harbouring MET dysregulations.

Primary Outcome Measure

Number of patients who consent to each arm. [ Time Frame: Up to 5 years. ]

Central Contacts

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