Anaplastic Large Cell Lymphoma, Cancer, Haematological Malignancy, Lymphoma, Lymphoproliferative Disorders, Malignant Neoplasm, Neoplasms by Histologic Type, Neoplasms by Site, Neuroblastoma, Renal Cell Carcinoma, Solid Tumour
Conditions
Keywords
Adult, Alectinib, ALK Tyrosine Kinase Receptor, Antineoplastic Agents, Cancer, Child, Malignancy, Malignant Neoplasms, Molecular Targeted Therapy, Mutation, Neoplasms by Histologic Site, Neoplasms by Site, Paediatric, Precision Medicine, Protein Kinase Inhibitors, Rare, Tumour-agnostic, Young adult
Brief summary
This clinical trial is looking at a drug called alectinib. Alectinib is approved as standard of care treatment for adult patients with certain types of lung cancer. This means it has gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Alectinib works in lung cancer patients with a particular mutation in their cancer known as ALK. Investigators now wish to find out if it will be useful in treating patients with other cancer types which have the same mutation. If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future. This trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.
Detailed description
DETERMINE Treatment Arm 01 (alectinib) aims to evaluate the efficacy of alectinib in ALK-positive rare\* adult, paediatric and teenage/young adult (TYA) cancers and in common cancers where an ALK mutation or amplification is considered to be infrequent. \*Rare is defined generally as incidence less than 6 cases in 100,000 patients (includes paediatric and teenagers/young adult cancers) or common cancers with rare alterations. This treatment arm has a target sample size of 30 evaluable patients. Sub-cohorts may be defined and further expanded to a target of 30 evaluable patients each. The ultimate aim is to translate positive clinical findings to the NHS (Cancer Drugs Fund) to provide new treatment options for rare adult, paediatric and TYA cancers. OUTLINE: Pre-screening: The Molecular Tumour Board makes a treatment recommendation for the patient based on molecularly-defined cohorts (See information on Master Screening Protocol below). Screening: Consenting patients undergo biopsy and collection of blood samples for research purposes. Treatment: Patients will receive alectinib until disease progression without clinical benefit, unacceptable adverse events (AEs) or withdrawal of consent. Patients will also undergo collection of blood samples at various intervals while receiving treatment and at EoT. After completion of study treatment, patients are followed up every 3 months for 2 years. THE DETERMINE TRIAL MASTER (SCREENING) PROTOCOL: Please see DETERMINE Trial Master (Screening) Protocol record (NCT05722886) for information on the DETERMINE Trial Master Protocol and applicable documents.
Interventions
DRUGAlectinib
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.
Sponsors
University of Manchester
University of Birmingham
Royal Marsden NHS Foundation Trust
Hoffmann-La Roche
Cancer Research UK
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion 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 next-generation sequencing 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. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow aspiration and/or trephine or lymph node biopsy samples may be taken. 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 defined in the protocol. These measurements should be performed to confirm the patient's eligibility. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Durable Clinical Benefit (DCB) | Disease assessments to be performed up to 24 weeks from the start of trial treatment. | DCB is defined as the absence of disease progression for at least 24 weeks from the start of trial treatment according to RECIST Version 1.1 criteria (or ir-RECIST or standard imaging criteria for specific disease e.g. RANO criteria) and, where relevant (e.g. for haematological malignancies), by standard bone marrow response assessment criteria. Alternative definitions of DCB based on different time points may be pre-specified for particular sub-cohorts if 24 weeks is not clinically relevant. The trial will report the proportion of patients with a DCB and 95% credible interval. |
| Objective Response (OR) | Disease assessments to be performed up to 24 weeks from the start of trial treatment. | An OR is defined as the confirmed occurrence of either a Complete Response (CR) or Partial Response (PR) according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 criteria (or immune related \[ir\]-RECIST or standard imaging criteria for specific disease e.g. Response Evaluation in Neuro Oncology criteria \[RANO\]). In patients with leukaemia, OR will be defined as the occurrence of CR, CRi (CR incomplete neutrophil recovery) or CRp (CR with incomplete platelet recovery). The trial will report the proportion of patients with an OR and 95% credible interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best percentage change in sum of target lesion / index lesion diameters (PCSD) | Disease assessment performed every 2 cycles of alectinib (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose of alectinib for up to 2 years. | PCSD is defined as the greatest decrease or least increase in the sum of target lesion diameters (RECIST) or index lesion diameters (irRECIST) as a percentage compared to the baseline measurement. The trial will report the mean PCSD and 95% credible interval. |
| Time to treatment discontinuation (TTD) | From first dose of alectinib to discontinuation of trial treatment up to 5 years with an average calculated and presented with results entry. | TTD is defined as the time from date of starting trial treatment to date of discontinuing trial treatment, in days estimated by the median of the posterior inverse gamma probability distribution. The trial will report the median TTD and 95% credible interval. |
| Progression-Free Survival time (PFS) | Disease assessment performed every 2 cycles of alectinib (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose of alectinib for up to 2 years. | PFS is defined as the time from date of starting trial treatment to date of progression or date of death without a previous progression recorded estimated by the median of the posterior inverse gamma probability distribution. |
| Time to Progression (TTP) | Disease assessment performed every 2 cycles of alectinib (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose of alectinib for up to 2 years. | TTP is defined as the time from date of starting trial treatment to date of progression or date of death without recorded progression censored rather than events. The trial will report the median TTP and 95% credible interval. |
| Occurrence of at least one Suspected Unexpected Serious Adverse Reaction (SUSAR) | From the time of consent until 28 days after last dose of alectinib (up to 5 years) or until patient starts another anti-cancer therapy, whichever came first. An average time frame will be presented with results entry. | The trial will report the number of patients who experience at least one SUSAR to alectinib. |
| Growth Modulation Index (GMI) | Disease assessment performed every 2 cycles of alectinib (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose of alectinib for up to 2 years. | GMI is defined as the ratio of TTP with the trial protocol treatment to TTP on the most recent prior line of therapy. The trial will report the mean GMI and 95% credible interval. |
| Overall Survival time (OS) | Time of death or up to 2 years after the EoT visit. | OS is defined as the time from date of starting trial treatment to date of death from any cause estimated by the median of the posterior normal probability distribution. |
| EQ-5D Standardised Area Under Index Value Curve (EQ5DSAUC) in adult patients | QoL surveys performed prior to inclusion, every cycle (each cycle is 28 days) and at EoT visit (up to 5 years). | For adult populations, two measures of Quality of Life (QoL) will be generated from patient completion of the EQ-5D-5L questionnaire. For each measure, scores based on responses from the questionnaire will be generated at each time point and the area under the curve generated by these scores over time will be calculated and standardised by the time frame. The trial will report the mean EQ5DSAUC and 95% credible interval. |
| Mean change from baseline in the PedsQL 4.0 Standardised Area Under total Scale Score Curve (PedsSAUC) in paediatric patients. | QoL surveys performed prior to inclusion, every cycle (each cycle is 28 days) and at EoT visit (up to 5 years). | For paediatric populations multiple measures of QoL will be generated from patient completion of the, PedsQL 4.0 (4 measures). The Summary Score from the questionnaire will be generated at each time point and the area under the curve generated by these scores over time will be calculated and standardised by the time frame. The trial will report the mean PedsSAUC and 95% credible interval. |
| Mean change from baseline in the PedsQL 4.0 Standardised Area Under total Scale Score Curve (PedsSAUC) in parents of paediatric patients | QoL surveys performed prior to inclusion, every cycle (each cycle is 28 days) and at EoT visit (up to 5 years). | For paediatric populations multiple measures of QoL will be generated from patient's parent completion of the PedsQL 4.0 (4 measures). The Summary Score from the questionnaire will be generated at each time point and the area under the curve generated by these scores over time will be calculated and standardised by the time frame. The trial will report the mean PedsSAUC and 95% credible interval. |
| Occurrence of at least one Grade 3, 4 or 5 alectinib related AE | From the time of consent until 28 days after last dose of alectinib (up to 5 years) or until patient starts another anti-cancer therapy, whichever came first. An average time frame will be presented with results entry. | Number of patients who experience at least one alectinib related Grade 3, 4 or 5 AE according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 |
| Duration of response (DR) | Disease assessment performed every 2 cycles of alectinib (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose of alectinib for up to 2 years. | DR is defined as the time from the date of the first confirmed CR or PR according to RECIST 1.1 or ir-RECIST or standard imaging criteria for specific disease e.g. RANO criteria to the date of disease progression. The trial will report the median DR and 95% credible interval. |
Other
| Measure | Time frame | Description |
|---|---|---|
| EORTC-QLQ-C30-Standardised Area Under Summary Score Curve (QLQSAUC) in adult patients. | QoL surveys performed prior to inclusion, every cycle (each cycle is 28 days) and at EoT visit (up to 5 years). | For adult populations, multiple measures of QoL will be generated from patient completion of the European Organisation for Research and Treatment of Cancer QLQ-C30 (EORTC-QLQ-C30) questionnaire (15 measures). For each patient the Summary Score from the questionnaire will be generated at each time point and the area under the curve generated by these scores over time will be calculated and standardised by the time frame. The trial will report the mean QLQSAUC and 95% credible interval. |
Countries
United Kingdom
Contacts
Primary ContactAida Sarmiento Castro
Outcome results
None listed