DETERMINE Trial Treatment Arm 01: Alectinib in Adult, Paediatric and Teenage/Young Adult Patients With ALK Positive Cancers

Launched by CANCER RESEARCH UK · Mar 14, 2023

Keywords

ClinConnect Summary

The DETERMINE Trial is studying a drug called alectinib, which is already used to treat certain types of lung cancer in adults. Researchers want to see if this medication can also help treat other types of cancers that share a specific mutation known as ALK. This trial is open to adults, teenagers, young adults, and children who have confirmed ALK-positive cancers, such as anaplastic large cell lymphoma, neuroblastoma, and others. To participate, individuals must meet certain health criteria, including having a recent biopsy and being able to undergo specific tests to check their organ function.

If you or your child are eligible and choose to participate, you can expect to take alectinib and attend regular follow-up visits to monitor your health and any side effects. The trial is currently recruiting participants, and if the results are positive, the study team hopes to work with healthcare providers to make alectinib available for more patients with these types of cancers in the future. It's important to know that there are specific guidelines regarding pregnancy and contraception for participants, as well as other health criteria to ensure safety during the trial.

Gender

ALL

Eligibility criteria

• • THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA WITHIN THE DETERMINE MASTER PROTOCOL (NCT05722886) AND WITHIN THE TREATMENT ARM 01 (ALECTINIB) OUTLINED BELOW\*
• • \*When alectinib-specific inclusion/exclusion criteria or precautions below differ from those specified in the Master Protocol, the alectinib-specific criteria will take precedence.
• Inclusion Criteria:
• • A. Confirmed diagnosis of an ALK-positive malignancy using an analytically validated method.
• B. 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 use one form of highly effective birth control method such as:
• • I. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation \[oral, intravaginal or transdermal\] II. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable) III. intrauterine device (IUD) IV. intrauterine hormone-releasing system (IUS) V. bilateral tubal occlusion VI. vasectomised partner VII. sexual abstinence
• • Effective from the first administration of alectinib, throughout the trial and for three months after the last administration of alectinib.
• C. Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from first administration of alectinib, throughout the trial and for three months after the last administration of alectinib:
• • Agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or sexual abstinence.
• • Non-vasectomised male patients with partners who are women of childbearing potential must also be willing to ensure that their partner uses a highly effective method of contraception, as in criterion B, above.
• • Male patients with pregnant or lactating partners must be advised to use barrier method contraception (e.g. condom) to prevent drug exposure of the foetus or neonate.
• • All male patients must refrain from donating sperm for the same period.
• • D. Patients must be able and willing to undergo a fresh tissue biopsy.
• • E. Paediatric patients (patients aged \<18 years) must have a body weight ≥40kg.
• • F. ADULT PATIENTS (≥18 years): Adequate organ function as per haematological and biochemical indices within the ranges shown below. These measurements should be performed to confirm the patient's eligibility.
• • Haemoglobin (Hb): ≥90 g/L (transfusion allowed)
• • Absolute neutrophil count (ANC): ≥1.5 × 10\^9/L (no granulocyte colony-stimulating factor \[GCSF\] support in preceding 72 hours)
• • Platelet count: ≥100×10\^9/L (unsupported for 72 hours)
• • Bilirubin: \<1.5 × upper limit of normal (ULN) or ≤2.5 × ULN if raised due to metastases
• • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): ≤2.5 × ULN or ≤5 × ULN if raised due to metastases
• • Coagulation - prothrombin (PT) (or international normalized ratio \[INR\]) and activated partial thromboplastin clotting time (aPTT): ≤1.5 × lower limit of normal (LLN)/ULN (unless patient is on anticoagulants e.g. warfarin \[INR should be stable and within indicated therapeutic range\], or direct oral anticoagulants \[DOAC\])
• • Estimated glomerular filtration rate (eGFR): eGFR: ≥30 mL/min (uncorrected value)
• • G. PAEDIATRIC PATIENTS (\<18 years): Adequate organ function as per haematological and biochemical indices within the ranges shown below. These measurements should be performed to confirm the patient's eligibility
• • Hb: ≥80 g/L (transfusion allowed)
• • ANC: ≥1.0×10\^9/L (no GCSF support in preceding 72 hours)
• • Platelet count: ≥75×10\^9/L (unsupported for 72 hrs)
• • Bilirubin: ≤1.5 × ULN for age or ≤2.5 × ULN if raised due to metastases
• • ALT and AST: ≤3.0 × ULN or ≤5 × ULN if raised due to metastases
• • Coagulation - PT or INR and aPTT: For patients not receiving therapeutic anticoagulation: INR and aPTT ≤1.5 × ULN for age. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen, e.g. warfarin (INR should be stable and within indicated therapeutic range) or DOAC.
• • eGFR: ≥60 mL/min/1.73m\^2
• Exclusion Criteria:
• • A. Diagnosis of ALK-positive non-small cell lung cancer.
• • B. Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or for three months following their last dose of alectinib.
• • C. Prior treatment with the same class of drug unless genetic profile demonstrates a mechanism of resistance known to be potentially sensitive to alectinib.
• • D. History of or radiological evidence of interstitial lung disease and/or pneumonitis. Prior localised radiotherapy related pneumonitis is permitted if resolved and off steroids and asymptomatic for \>6 months.
• • E. Patients at risk of gastrointestinal (GI) perforation e.g. history of diverticulitis, concomitant use of medicinal product with a recognized risk of gastrointestinal perforation (unless patient has also been co-prescribed gastric protection).
• • • Patients who present with a GI primary tumour or metastases to the GI tract may be considered.
• • F. Patient unable to swallow or tolerate oral medication or any GI disorder that may affect absorption of oral medications, such as malabsorption syndrome or following major bowel resection. Paediatric patients will be excluded if they are unable to swallow the capsules, as per the dosing schedule (150 mg dose strength).
• • G. Patients with clinically significant pre-existing cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias (within three months), or New York Heart Association (NYHA) class III or IV congestive heart failure.
• • Patients with a cerebrovascular event (including stroke or transient ischaemic attack \[TIA\]), or cardiovascular event (including acute myocardial infarction \[MI\]), within three months before the first dose of alectinib.
• • • Patients with primary CNS tumours may be considered unless intra-tumoural bleeding has occurred within 2 weeks of the first dose of alectinib, and patients with punctate CNS haemorrhages \<3 mm may be considered.
• • H. History of organ transplantation.
• • I. Symptomatic bradycardia for age.
• • J. Known hypersensitivity to alectinib or any of the excipients. See the current alectinib (Alecensa® 150 mg hard capsules) SmPC relevant to the site (e.g. Great Britain or Northern Ireland \[NI\]) for the full list.
• • K. Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment, or anticipation of need for such a vaccine during alectinib treatment or within six months after the final dose of alectinib.
• L. Active hepatitis B or C virus or known human immunodeficiency virus (HIV) positivity or acquired immune deficiency syndrome (AIDS) related illness. Patients with history of testing positive for HIV infection are eligible provided the each of the following conditions are met:
• • CD4 count ≥350/μL;
• • undetectable viral load;
• • receiving antiretroviral therapy (ART) that does not interact with IMP (patients should be on established ART for at least four weeks); and
• • no HIV/AIDS-associated opportunistic infection in the last 12 months.
• • M. Familial or personal history of congenital bone disorders, bone metabolism alterations or known osteopenia in the patient.
• • N. Any clinically significant concomitant disease or condition (or it's treatment) that could interfere with, the conduct of the trial or absorption of oral medications that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this trial.