Study of Lorlatinib (PF-06463922)



Status:Recruiting
Conditions:Brain Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:1 - 90
Updated:8/22/2018
Start Date:September 1, 2017
End Date:December 2020
Contact:Araz Marachelian, MD
Email:amarachelian@chla.usc.edu
Phone:323-361-5687

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Phase 1 Study of Lorlatinib (PF-06463922), an Oral Small Molecule Inhibitor of ALK/ROS1, for Patients With ALK-Driven Relapsed or Refractory Neuroblastoma

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).

Lorlatinib is a novel inhibitor across ALK variants, including those resistant to crizotinib.
An adult phase 1 study established an RP2D of 100mg QD for lorlatinib. 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).

Lorlatinib will be administered orally via tablets or via oral dispersion if patient is
unable to swallow tablets whole

All patients will participate in mandatory pharmacokinetic testing.

Inclusion Criteria:

- Patients must have a diagnosis of neuroblastoma either by histologic verification of
neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased
urinary catecholamines

- Patients are required to have an activating ALK aberration in their tumor detected by
certified assay (i.e. CLIA in the US.) prior to registration. The report from this
test is required to be submitted for eligibility. Patients with at least one of the
following genetic features in their tumor will be considered to have an activating ALK
aberration:

1. An ALK activating mutation;

2. ALK amplification (> 10 signals of the ALK gene);

3. Presence of any ALK fusion protein that arises from a chromosomal translocation.

- Patients must have high risk neuroblastoma according to COG risk classification at the
time of study registration. Patients who were initially considered low or intermediate
risk, but then reclassified as high risk are also eligible.

- Patients must have at least ONE of the following: 1) Recurrent/progressive disease at
any time prior to study enrollment, 2) Refractory disease, 3) Persistent disease

- Patients must have at least ONE of the following: 1) Bone disease, 2) Any amount of
neuroblastoma tumor cells in the bone marrow, 3) At least one soft tissue lesion that
meets criteria for a TARGET lesion, 4) At least one non-target soft tissue lesion that
is not measurable, but had a biopsy positive for neuroblastoma and/or
ganglioneuroblastoma at any time prior to enrollment or is MIBG avid

- Patients must have a Lansky (≤16 years) or Karnofsky (> 16 years) score of at least 50

- Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

- Patients must not have been previously treated with lorlatinib.

- Patients must not have received any of the specified therapies as stated in the
protocol in the time period prior to registration

- Patients must not be receiving any other anti-cancer agents or radiotherapy at the
time of study entry or while on study.

- Patients must not be receiving other investigational medications (covered under
another IND) within 30 days of study entry or while on study.

- Patients must not be receiving chronic systemic corticosteroids at doses greater than
physiologic dosing (inhaled corticosteroids acceptable).

- Patient must meet the organ function and system function requirements as stated in the
protocol

Exclusion Criteria:

- Pregnancy, breast feeding, or unwillingness to use effective contraception during the
study.

- Patients who, in the opinion of the investigator, may not be able to comply with the
safety monitoring requirements of the study.

- Patients with disease of any major organ system that would compromise their ability to
withstand therapy.

- Patients who have received prior allogeneic stem cell transplant

- Patients who are on hemodialysis.

- Patients with an active or uncontrolled infection.

- Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or
hepatitis C.

- Patient declines participation in NANT 2004-05, the NANT Biology Study
We found this trial at
13
sites
Chapel Hill, North Carolina 27599
(919) 962-2211
Univ of North Carolina Carolina’s vibrant people and programs attest to the University’s long-standing place...
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Ann Arbor, MI 48109Bus: -
Ann Arbor, Michigan 48109
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Boston, Massachusetts 02115
Phone: 617-632-3725
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5721 S. Maryland Avenue
Chicago, Illinois 60637
Phone: 773-843-3943
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3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
 1-513-636-4200 
Phone: 513-636-9866
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
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4650 Sunset Blvd
Los Angeles, California 90027
 (323) 660-2450
Phone: 323-361-5687
Childrens Hospital Los Angeles Children's Hospital Los Angeles is a 501(c)(3) nonprofit hospital for pediatric...
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South 34th Street
Philadelphia, Pennsylvania 19104
 215-590-1000
Phone: 215-590-0965
Children's Hospital of Philadelphia Since its start in 1855 as the nation's first hospital devoted...
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1600 Divisadero Street
San Francisco, California 94115
888.689.8273
Phone: 415-476-3831
UCSF Helen Diller Family Comprehensive Cancer Center UCSF’s long tradition of excellence in cancer research...
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1405 Clifton Road NE
Atlanta, Georgia 30322
404-785-6000
Phone: 404-785-0853
Children's Healthcare of Atlanta Whether treating a toddler in an emergency or supporting a teen...
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Aurora, Colorado 80045
Phone: 720-777-8856
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Fort Worth, Texas 76104
Phone: 682-885-4007
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Seattle, Washington 98105
Phone: 206-987-5783
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555 University Avenue
Toronto, Ontario M5G 1X8
Phone: 416-813-7654
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