💬In plain words
What the trial is, and whether it could suit you
This is an open-label, phase I-II dose-escalation and expansion study designed to define the recommended dose of brigatinib as monotherapy in pediatric and young adult patients with ALK+ ALCL, IMT or other solid tumors and to evaluate the pharmacokinetics (PK), (long-term) safety, and efficacy of brigatinib in these children.
Sign in to get the eligibility rules as simple questions to take to your doctor.
📋 Eligibility rules (as published)
Inclusion Criteria:
1. Patients must be 1 and \< 26 years of age at the time of enrollment, and able to swallow brigatinib tablets at the time of enrollment, with a minimum weight of 10 kg. Note: for phase 1 only patients ≤18 years old will be eligible, A liquid formulation for children with a weight lower than 10 kg or for those that cannot swallow tablets is in development.
2. Patients must have a confirmed diagnosis of cancer histologically at baseline. In patients where a repeat biopsy at relapse (or moment of refractory disease) is considered not feasible by the treating physician, archived material from diagnosis needs to be available for central review.
3. Patients are required to provide prior results showing an activating ALK aberration in the tumor per local laboratory results, and material needs to be available for central laboratory confirmation of ALK status. For ALK+ ALCL, detection of ALK with immunohistochemistry (IHC) is sufficient for inclusion, all others require molecular evidence of a ALK fusion gene or mutation by FISH, PCR or NGS. ALK detection will be confirmed centrally with FISH.
4. For Phase 1:
* Patients with ALCL must be relapsed/refractory or intolerant to standard therapies. Refractory disease for ALCL is defined as:
o no response to ALCL99/other standard of care chemotherapy (SD or PD of measurable lesions), and/or
o MRD-positivity by qualitative PCR for NPM-ALK prophase after one block ALCL99/other standard of care chemotherapy (before the second course of chemotherapy).
* Patients with relapsed/refractory (R/R) IMT must not be suitable for curative surgical resection without causing mutilation. Newly diagnosed patients with unresectable ALK+ IMT, or when surgery would imply severe mutilation may also be included, as well as metastatic disease.
* Patients with other solid tumors (excluding IMT) must have relapsed or refractory disease.
5. For Phase 2, patients must have measurable and/or evaluable disease:
* Patients with ALCL must be relapsed/refractory. Refractory disease for ALCL is defined as:
* no response to ALCL99/other standard of care chemotherapy (SD or PD of measurable lesions), and/or
* MRD-positivity by qualitative PCR for NPM-ALK prophase after one block ALCL99/other standard of care chemotherapy (before the second course of chemotherapy).
* Patients with R/R IMT Relapsed/refractory ALK+ IMT, or newly diagnosed, including advanced and metastatic, ALK+ IMT which cannot be surgically resected without causing mutilation
6. Performance Status: Karnofsky performance status ≥40% for patients \>16 years of age or Lansky Play Scale ≥40% for patients ≤16 years of age.
7. Patients must not be receiving other investigational medications (defined as medicinal products not yet approved for any indications, including alternative/herbal therapies) within 30 days of first dose of study drug or while on study.
8. For patients receiving prior therapy:
* Patients who already received previous treatment with ALK inhibitors except for brigatinib can be included in this study.
* Patients must have recovered to Grade \<2 NCI CTCAE v5.0 or to baseline, from any nonhematologic toxicities (except alopecia and peripheral neuropathy) due to previous therapy.
* Patients who relapsed while receiving cytotoxic therapy: at least 14 days must have passed since the completion of the last dose of chemotherapy before the first dose of brigatinib can be given.
* Patients who have experienced relapse after a prior HSCT are eligible, provided they have no evidence of acute or chronic graft-versus-host disease (GVHD), are not receiving GVHD prophylaxis or treatment, and are at least 45 days posttransplant at the time of enrollment.
* Hematopoietic growth factors: before the first dose of brigatinib, at least 7 days must have passed since completion of therapy with granulocyte colony-stimulating factor or other growth factors, and at least 14 days must have passed since completion of therapy with pegfilgrastim.
* Biologics and Targeted Therapies:
o Immunotherapy: Before the first dose of brigatinib, at least 30 days must have passed after the completion of any type of immunotherapy, (i.e. monoclonal antibodies \[anti-PD1/PDL1\], tumor vaccines, chimeric antigen receptor \[CAR\] T cells, etc.).
o Other: before the first dose of brigatinib, at least 7 days must have passed since the last dose of a biologic agent. For agents that have known adverse events (AEs) occurring beyond 7 days after administration, this period must be extended beyond the time during which AEs are known to occur. The duration of this interval must be discussed with the sponsor's medical monitor/designee.
o Immunosuppressive therapy: Before the first dose of brigatinib, at least 14 days must have passed after the completion of immunosuppressive therapy (including regimens following stem cell transplant).
o For symptomatic patients that urgently need relief (i.e. airway obstruction), therapeutic doses of corticosteroids may be administered for a short course (up to 5 days).
o Radiotherapy (XRT): No washout period is necessary for radiation given to any extramedullary site other than the CNS and lungs; ≥45 days must have passed if patient received prior total body irradiation or craniospinal or cranial XRT; ≥28 days must have passed if patient received radiotherapy to the lung. For patients receiving XRT to both lungs, or in case of stereotactic radiotherapy, the PIs should be consulted before inclusion.
9. Patients must meet the organ function and system function requirements as stated below:
* Patients must have adequate renal and hepatic function as indicated by the following laboratory values:
o Patient's serum creatinine must be ≤ 1.5 x institutional upper limit of normal (ULN) according to age. If the serum creatinine is greater than 1.5 x institutional ULN, the patient must have a radioisotope GFR ≥ 70mL/min/