At a glance
ClinicalIndex Comparison Record- ✓Activating ALK aberration (mutation, amplification >10 signals, or fusion) confirmed by CLIA-certified assay
- ✓High-risk neuroblastoma diagnosis by histology, bone marrow involvement, or elevated urinary catecholamines
- ✓High-risk disease per COG classification at registration (or reclassified to high-risk)
- ✓Recurrent/progressive disease OR refractory disease (best response ≤SD after ≥4 induction cycles) OR persistent disease (best response <PR after ≥4 induction cycles)
- ✕Prior treatment with lorlatinib (prior ALK inhibitors other than lorlatinib are allowed)
- ✕Prior allogeneic stem cell transplant
- ✕Concomitant anti-cancer agents or radiotherapy
- ✕Active or uncontrolled infection
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
Phase 1 Study of Lorlatinib (PF-06463922), an Oral Small Molecule Inhibitor of ALK/ROS1, for Patients With ALK-Driven Relapsed or Refractory Neuroblastoma
In Brief
A Phase 1 clinical trial evaluating Lorlatinib, Cyclophosphamide, and 2 other interventions for Neuroblastoma. Completed, enrolled 65 participants across 13 sites in 4 countries.
Detailed Summary
Lorlatinib is a novel inhibitor across ALK variants, including those resistant to crizotinib. In this first pediatric phase 1 trial of lorlatinib, the drug will be utilized as a single agent and in combination with chemotherapy in patients with relapsed/refractory neuroblastoma. The dose escalation phase of this study (Cohort A1) uses a traditional Phase I 3+3 design. Once a recommended phase 2 pediatric dose is identified, an expansion cohort of 6 patients (Cohort B1), within which ALKi naïve patients will be prioritized, will be initiated. Parallel cohorts will be initiated in adults or patients with large BSA (Cohort A2) and in combination with chemotherapy upon establishing RP2D (Cohort B2).
Study Details
Timeline
Interventions
Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC \> 2000/mm\^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy. Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.