NANT 2015-02: A Phase 1 Study of Lorlatinib (PF-06463922)

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).

Conditions

• Neuroblastoma

Interventions

DRUG

Lorlatinib

Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.

DRUG

Cyclophosphamide

Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle

DRUG

Topotecan

Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle

DRUG

Filgrastim/pegfilgrastim

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.

Sponsors & Collaborators

• Pfizer

  collaborator INDUSTRY

• University of Southern California

  collaborator OTHER

• Solving Kids' Cancer US/EU

  collaborator UNKNOWN

• Children's Neuroblastoma Cancer Foundation

  collaborator UNKNOWN

• The Band of Parents

  collaborator UNKNOWN

• The Evan Foundation

  collaborator OTHER

• Wade's Army

  collaborator UNKNOWN

• Ronan Thompson Foundation

  collaborator UNKNOWN

• The Catherine Elizabeth Blair Memorial Foundation

  collaborator UNKNOWN

• Cookies for Kids' Cancer

  collaborator OTHER

• New Approaches to Neuroblastoma Therapy Consortium

  lead OTHER

Principal Investigators

• Yael Mosse, MD · Children's Hospital of Philadelphia

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

1 Year

Max Age

99 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-09-05

Primary Completion

2024-08-22

Completion

2025-01-31

FDA Drug

Yes

Countries

• United States
• Canada
• France
• United Kingdom

Study Locations