Study of Lorlatinib (PF-06463922)

Description

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 Start Date

September, 05 2017

Estimated Completion Date

December 2020

Interventions

  • Drug: Cyclophosphamide
  • Drug: Topotecan
  • Drug: Lorlatinib

Study ID

New Approaches to Neuroblastoma Therapy Consortium -- NANT2015-02

Status

Recruiting

Trial ID

NCT03107988

Study Type

Interventional

Trial Phase

Phase 1

Enrollment Quota

40

Sponsor

New Approaches to Neuroblastoma Therapy Consortium

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

Gender

All

Ages

1 Year to 90 Years

Accepts Healthy Volunteers

No

Study Locations and Contact Information (50)

Study Location Distance Name Phone Email
Childrens Hospital Boston DanaFarber Cancer Institute - Boston, Massachusetts 2.6 miles Suzanne Shusterman MD 617-632-3725 suzanne_shusterman@dfci.harvard.edu
Childrens Hospital Boston DanaFarber Cancer Institute - Boston, Massachusetts 2.6 miles Suzanne Shusterman MD 617-632-3725 suzanne_shusterman@dfci.harvard.edu
Childrens Hospital Boston DanaFarber Cancer Institute - Boston, Massachusetts 2.6 miles Suzanne Shusterman MD 617-632-3725 suzanne_shusterman@dfci.harvard.edu
Childrens Hospital Boston DanaFarber Cancer Institute - Boston, Massachusetts 2.6 miles Suzanne Shusterman MD 617-632-3725 suzanne_shusterman@dfci.harvard.edu
Childrens Hospital Boston DanaFarber Cancer Institute - Boston, Massachusetts 2.6 miles Suzanne Shusterman MD 617-632-3725 suzanne_shusterman@dfci.harvard.edu
University of North Carolina - Chapel Hill, North Carolina 616.4 miles Patrick Thompson MD None patom@email.unc.edu
University of North Carolina - Chapel Hill, North Carolina 616.4 miles Patrick Thompson MD None patom@email.unc.edu
University of North Carolina - Chapel Hill, North Carolina 616.4 miles Patrick Thompson MD None patom@email.unc.edu
University of North Carolina - Chapel Hill, North Carolina 616.4 miles Patrick Thompson MD None patom@email.unc.edu
University of North Carolina - Chapel Hill, North Carolina 616.4 miles Patrick Thompson MD None patom@email.unc.edu
CS Mott Childrens Hospital - Ann Arbor, Michigan 645.2 miles Rajen Mody MD None rmody@umich.edu
CS Mott Childrens Hospital - Ann Arbor, Michigan 645.2 miles Rajen Mody MD None rmody@umich.edu
CS Mott Childrens Hospital - Ann Arbor, Michigan 645.2 miles Rajen Mody MD None rmody@umich.edu
CS Mott Childrens Hospital - Ann Arbor, Michigan 645.2 miles Rajen Mody MD None rmody@umich.edu
CS Mott Childrens Hospital - Ann Arbor, Michigan 645.2 miles Rajen Mody MD None rmody@umich.edu
University of Chicago Comer Childrens Hospital - Chicago, Illinois 848.0 miles Susan L Cohn MD 773-702-2571 Scohn@peds.bsd.uchicago.edu
University of Chicago Comer Childrens Hospital - Chicago, Illinois 848.0 miles Susan L Cohn MD 773-702-2571 Scohn@peds.bsd.uchicago.edu
University of Chicago Comer Childrens Hospital - Chicago, Illinois 848.0 miles Susan L Cohn MD 773-702-2571 Scohn@peds.bsd.uchicago.edu
University of Chicago Comer Childrens Hospital - Chicago, Illinois 848.0 miles Susan L Cohn MD 773-702-2571 Scohn@peds.bsd.uchicago.edu
University of Chicago Comer Childrens Hospital - Chicago, Illinois 848.0 miles Susan L Cohn MD 773-702-2571 Scohn@peds.bsd.uchicago.edu
Childrens Healthcare of Atlanta - Atlanta, Georgia 932.0 miles Kelly Goldsmith MD 404-785-0853 kgoldsmith@emory.edu
Childrens Healthcare of Atlanta - Atlanta, Georgia 932.0 miles Kelly Goldsmith MD 404-785-0853 kgoldsmith@emory.edu
Childrens Healthcare of Atlanta - Atlanta, Georgia 932.0 miles Kelly Goldsmith MD 404-785-0853 kgoldsmith@emory.edu
Childrens Healthcare of Atlanta - Atlanta, Georgia 932.0 miles Kelly Goldsmith MD 404-785-0853 kgoldsmith@emory.edu
Childrens Healthcare of Atlanta - Atlanta, Georgia 932.0 miles Kelly Goldsmith MD 404-785-0853 kgoldsmith@emory.edu
Cook Childrens Healthcare System - Fort Worth, Texas 1,578.4 miles Meaghan Granger MD 682-885-4007 mgranger@cookchildrens.org
Cook Childrens Healthcare System - Fort Worth, Texas 1,578.4 miles Meaghan Granger MD 682-885-4007 mgranger@cookchildrens.org
Cook Childrens Healthcare System - Fort Worth, Texas 1,578.4 miles Meaghan Granger MD 682-885-4007 mgranger@cookchildrens.org
Cook Childrens Healthcare System - Fort Worth, Texas 1,578.4 miles Meaghan Granger MD 682-885-4007 mgranger@cookchildrens.org
Cook Childrens Healthcare System - Fort Worth, Texas 1,578.4 miles Meaghan Granger MD 682-885-4007 mgranger@cookchildrens.org
Children Hospital of Colorado - Aurora, Colorado 1,759.8 miles Margaret Macy MD 720-777-8856 Margaret.macy@childrenscolorado.org
Children Hospital of Colorado - Aurora, Colorado 1,759.8 miles Margaret Macy MD 720-777-8856 Margaret.macy@childrenscolorado.org
Children Hospital of Colorado - Aurora, Colorado 1,759.8 miles Margaret Macy MD 720-777-8856 Margaret.macy@childrenscolorado.org
Children Hospital of Colorado - Aurora, Colorado 1,759.8 miles Margaret Macy MD 720-777-8856 Margaret.macy@childrenscolorado.org
Children Hospital of Colorado - Aurora, Colorado 1,759.8 miles Margaret Macy MD 720-777-8856 Margaret.macy@childrenscolorado.org
Childrens Hospital and Regional Medical Center Seattle - Seattle, Washington 2,487.2 miles Julie R Park MD 206-987-1947 Julie.park@seattlechildrens.org
Childrens Hospital and Regional Medical Center Seattle - Seattle, Washington 2,487.2 miles Julie R Park MD 206-987-1947 Julie.park@seattlechildrens.org
Childrens Hospital and Regional Medical Center Seattle - Seattle, Washington 2,487.2 miles Julie R Park MD 206-987-1947 Julie.park@seattlechildrens.org
Childrens Hospital and Regional Medical Center Seattle - Seattle, Washington 2,487.2 miles Julie R Park MD 206-987-1947 Julie.park@seattlechildrens.org
Childrens Hospital and Regional Medical Center Seattle - Seattle, Washington 2,487.2 miles Julie R Park MD 206-987-1947 Julie.park@seattlechildrens.org
Lucille Salter Packer Childrens Hospital Stanford University - Palo Alto, California 2,694.5 miles Sheri Spunt MD 650-723-5535 sspunt@stanford.edu
Lucille Salter Packer Childrens Hospital Stanford University - Palo Alto, California 2,694.5 miles Sheri Spunt MD 650-723-5535 sspunt@stanford.edu
Lucille Salter Packer Childrens Hospital Stanford University - Palo Alto, California 2,694.5 miles Sheri Spunt MD 650-723-5535 sspunt@stanford.edu
Lucille Salter Packer Childrens Hospital Stanford University - Palo Alto, California 2,694.5 miles Sheri Spunt MD 650-723-5535 sspunt@stanford.edu
Lucille Salter Packer Childrens Hospital Stanford University - Palo Alto, California 2,694.5 miles Sheri Spunt MD 650-723-5535 sspunt@stanford.edu
UCSF Helen Diller Family Comprehensive Cancer Center - San Francisco, California 2,699.8 miles Katherine K Matthay MD 415-476-3831 matthayK@peds.ucsf.edu
UCSF Helen Diller Family Comprehensive Cancer Center - San Francisco, California 2,699.8 miles Katherine K Matthay MD 415-476-3831 matthayK@peds.ucsf.edu
UCSF Helen Diller Family Comprehensive Cancer Center - San Francisco, California 2,699.8 miles Katherine K Matthay MD 415-476-3831 matthayK@peds.ucsf.edu
UCSF Helen Diller Family Comprehensive Cancer Center - San Francisco, California 2,699.8 miles Katherine K Matthay MD 415-476-3831 matthayK@peds.ucsf.edu
UCSF Helen Diller Family Comprehensive Cancer Center - San Francisco, California 2,699.8 miles Katherine K Matthay MD 415-476-3831 matthayK@peds.ucsf.edu

ClinicalTrialsLocator.com provides clinical trial listings in an easy to view format. All clinical trial information is pulled directly from ClinicalTrials.gov. This website does not guarantee acceptance into any clinical trial, and is not responsible for adverse events that may be incurred from a clinical trial.