ALK fusion-positive extracranial solid or primary CNS tumors who have progressed following prior treatment or who have no satisfactory treatment available MedDRA version: 21.0 Level: LLT Classification code 10028992 Term: Neoplasm CNS System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864
Conditions
Interventions
Product Name: Alectinib
Product Code: Ro 542-4802
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ALECTINIB
Current Sponsor code: Ro 542-4802/F03-02
Other descriptive name: ALECTINIB Ro 542-48
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age at study entry =8 weeks, in the investigator's judgment • Adequate performance status (For patients = 50% and for patients >= 16 years old: Karnofsky Performance Status should be >= 50%) • Patients with adequate end-organ function • Females of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs during the treatment period and for at least 3 months after the final dose of study drug • Females of childbearing potential must have a negative serum pregnancy test during screening and be neither breastfeeding nor intending to become pregnant during study participation • Males who are not surgically sterile must agree to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating sperm, during the treatment period and for at least 3 months after the final dose of study drug Are the trial subjects under 18? yes Number of subjects for this age range: 42 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Medical history of prior use of ALK inhibitors, any gastrointestinal (GI) disorder that may affect absorption of oral medications, organ transplant, recent stem cell infusions (with or without traumatic brain injury) • History of hypersensitivity to any of the additives in the alectinib drug formulation to be used in the study • Substance abuse within 12 months prior to screening, in the investigator's judgment • Familial or personal history of congenital bone disorders, bone metabolism alterations or osteopenia • Treatment with investigational therapy 28 days prior to initiation of study drug • Liver disease • Abnormal levels of creatinine or glomerular filtration rate (GFR) • National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0) Grade >=3 toxicities attributed to any prior therapy such as radiotherapy (excluding alopecia), which have not shown improvement and are strictly considered to interfere with alectinib • Co-administration of anti-cancer therapies other than those administered in this study • Active hepatitis B or C virus (HBV, HBC) or known human immunodeficiency virus (HIV) positivity or Acquired immunodeficiency syndrome (AIDS)-related illness • Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications or that would, in the opinion of the Principal Investigator, pose an unacceptable risk to the patient in this study • Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures • Planned procedure or surgery during the study except as permitted treatment • Infection considered by the investigator to be clinically uncontrolled or of unacceptable risk to the patient upon induction of neutropenia such as fungal infection or bacterial infection or neutropenic fever or patients who have received <5 days of appropriate therapeutic antibiotic therapy for an identified infection • Pregnant or breastfeeding women, or intending to become pregnant during the study or within 3 months after the final dose of alectinib
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To confirm the recommended Phase II dose (RP2D) in pediatric patients as the dose equivalent matching adult exposure without dose-limiting toxicity (DLT) • To evaluate the safety and tolerability of alectinib as a single agent • To characterize the pharmacokinetics of alectinib and its major metabolite M4 and to confirm the pediatric RP2D • To evaluate the anti-cancer activity of alectinib at the pediatric RP2D dose;Secondary Objective: • To evaluate the efficacy of alectinib in all enrolled patients receiving alectinib at the pediatric RP2D, in CNS patients and in solid patients. • To evaluate the safety of single-agent alectinib on growth and development • To evaluate potential relationships between drug exposure and the efficacy and safety of alectinib;Primary end point(s): 1. Incidence of dose-limiting toxicities (DLTs) assessed during the first cycle of study treatment 2. Incidence and severity of adverse events by severity determined according to the NCI-CTCAE v5.0, as well as changes from baseline in physical findings, targeted vital signs, clinical lab test results and ECG parameters 3. Plasma concentrations of alectinib and its metabolites (M4) at specified timepoints 4. Confirmed objective response rate (ORR) as determined by blinded independent central review;Timepoint(s) of evaluation of this end point: 1. Assessment during the first cycle 2-3. Baseline to 5 years 4. When a minimum of 10 and 30 pediatric patients have been enrolled in the expansion portion of the study and followed for at least 6 months, respectively. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Key efficacy endpoint; Confirmed ORR as determined by the investigator, Duration of response (DOR), Time to response (TTR), Clinical benefit rate (CBR), as determined by blinded independent central review and by the investigator 2. Overall survival (OS) 3. Change from baseline in growth patterns (relative to age specific standards for height, weight, and head circumference), in development patterns and neurocognitive outcome (using age-appropriate measures/scales) 4. Relationship between plasma concentration or PK parameters for alectinib and efficacy or safety endpoints;Timepoint(s) of evaluation of this end point: 1-4. When a minimum of 10 and 30 pediatric patients have been enrolled in the expansion portion of the study and followed for at least 6 months, respectively. When patients have been followed up to 5 years. | — |
Countries
Australia, Canada, China, Denmark, France, Germany, Hong Kong, Italy, Korea, Republic of, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed