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SF1126 for Patients With Relapsed or Refractory Neuroblastoma

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ClinicalTrials.gov Identifier: NCT02337309
Recruitment Status : Recruiting
First Posted : January 13, 2015
Last Update Posted : November 6, 2017
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
Brief Summary:

SF1126 is a novel inhibitor of PI3 kinase and mTOR that includes an active moiety (consisting of LY294002) linked to an RGDS tetrapeptide that targets the active agent to integrin expressing tissues. In this first pediatric phase 1 trial of SF1126, dose escalation will follow a 3+3 dose escalation design. Once a recommended phase 2 pediatric dose is identified, an expansion cohort of 10 patients with tumors with MYCN amplification, Mycn expression, or Myc expression will be treated.

Funding Source - FDA OOPD


Condition or disease Intervention/treatment Phase
Neuroblastoma Drug: SF1126 Phase 1

Detailed Description:
Inhibitors of the PI3 kinase pathway have demonstrated preclinical activity in neuroblastoma. This activity may derive in part from destabilizing Mycn protein, impeding tumor angiogenesis, and/or other effects. SF1126 is a novel inhibitor of PI3 kinase and mTOR that includes an active moiety (consisting of LY294002) linked to an RGDS tetrapeptide that targets the active agent to integrin expressing tissues. In preclinical studies, SF1126 results in marked concentration of LY294002 into tumors. In an adult phase 1 trial, a maximum tolerated dose of SF1126 was not identified up to doses of 1110 mg/m2 administered intravenously twice weekly on a continuous schedule. In this first pediatric phase 1 trial of SF1126, dose escalation will follow a 3+3 dose escalation design. Once a recommended phase 2 pediatric dose is identified, an expansion cohort of 10 patients with tumors with MYCN amplification, Mycn expression, or Myc expression will be treated. All patients will participate in mandatory pharmacokinetic testing. Additional optional correlative studies will evaluate potential predictive markers and potential pharmacodynamic markers, including PTEN and PIK3CA aberrations, Myc / Mycn expression, and Myc / pS6 levels in peripheral blood mononuclear cells.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of SF1126 for Patients With Relapsed or Refractory Neuroblastoma
Study Start Date : July 2015
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
SF1126
Patients will receive SF1126 IV over 90 minutes on Days 1 and 4 of each week during each cycle.
Drug: SF1126
SF1126 in IV form with be given to patients on this study.


Outcome Measures

Primary Outcome Measures :
  1. Toxicities, based on the CTCAE criteria, will be used to measure the severity of adverse events [ Time Frame: 6 months ]
    Toxicity will be graded using the CTCAE criteria, version 4. The CTCAE provides descriptive terminology and a grading scale for each adverse event listed. A copy of the CTCAE can be downloaded from the CTEP home page (http://ctep.cancer.gov).


Secondary Outcome Measures :
  1. Evaluation of response [ Time Frame: After day 1 of week 4 of cycles 2, 4, and 6 ]
    Response will be determined by the evaluation of CT/MRI scans and bone marrow biopsy.

  2. Pharmacokinetics: Parameters include AUC, clearance, Cmax, Tmax, & terminal half-life for SF1101 & SF1174. With rapid conversion of SF1126 to SF1101, only AUC, clearance, Cmax & Tmax are calculated for SF1126. [ Time Frame: Day 1, cycle 1 ]
    Plasma samples will be collected from patients at 9 time points on Day 1 of the first cycle.


Eligibility Criteria

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Ages Eligible for Study:   1 Year to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 must have high-risk neuroblastoma according to COG risk classification at the time of study enrollment.
  • 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.
  • 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 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 requirements as stated in the protocol.

Exclusion Criteria:

  • Pregnancy, breast feeding, or unwillingness to use effective contraception during the study.
  • Patients status post-allogeneic stem cell transplant are not eligible.
  • 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 are on hemodialysis.
  • Patients with an active or uncontrolled infection.
  • Patients with known intraparenchymal brain metastasis at study entry are excluded due to poor CNS penetration of SF1126.
  • Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C.
  • Patient declines participation in NANT 2004-05, the NANT Biology Study.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02337309


Contacts
Contact: Araz Marachelian, MD 323-361-8573 amarachelian@chla.usc.edu

Locations
United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027-0700
Contact: Araz Marachelian, MD    323-361-5687    amarachelian@chla.usc.edu   
Lucille Salter Packer Children's Hospital, Stanford University Recruiting
Palo Alto, California, United States, 94305
Contact: Sheri Spunt, MD         
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94143
Contact: Katherine K. Matthay, MD    415-476-3831    matthayK@peds.ucsf.edu   
United States, Colorado
Children Hospital of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Margaret Macy, MD    720-777-8856    Margaret.macy@childrenscolorado.org   
United States, Georgia
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus Recruiting
Atlanta, Georgia, United States, 30322
Contact: Kelly Goldsmith, MD    404-785-0853    kgoldsm@emory.edu   
United States, Illinois
University of Chicago Comer Children's Hospital Recruiting
Chicago, Illinois, United States, 60637
Contact: Susan L. Cohn, MD    773-702-2571    scohn@peds.bsd.uchicago.edu   
United States, Massachusetts
Childrens Hospital Boston, Dana-Farber Cancer Institute. Recruiting
Boston, Massachusetts, United States, 02115
Contact: Suzanne Shusterman, MD    617-632-3725    suzanne_shusterman@dfci.harvard.edu   
United States, Michigan
C.S Mott Children's Hospital Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Rajen Mody, MD       rmody@umich.edu   
United States, North Carolina
University of North Carolina Not yet recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Patrick Thompson, MD       patom@email.unc.edu   
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229-3039
Contact: Brian Weiss, MD    513-636-9863    brian.weiss@chmcc.org   
United States, Texas
Cook Children's Healthcare System Recruiting
Fort Worth, Texas, United States, 76104
Contact: Meaghan Granger, MD    682-885-4007    mgranger@cookchildrens.org   
United States, Washington
Children's Hospital and Regional Medical Center - Seattle Recruiting
Seattle, Washington, United States, 98105
Contact: Julie R. Park, MD    206-987-1947    Julie.park@seattlechildrens.org   
Sponsors and Collaborators
New Approaches to Neuroblastoma Therapy Consortium
SignalRX Pharmaceuticals, Inc.
University of Southern California
Investigators
Principal Investigator: Steven DuBois, MD Dana-Farber Cancer Institute
More Information

Responsible Party: New Approaches to Neuroblastoma Therapy Consortium
ClinicalTrials.gov Identifier: NCT02337309     History of Changes
Other Study ID Numbers: NANT 2014-01
N14-01 ( Other Identifier: NANT Consortium )
R01FD005740 ( Other Grant/Funding Number: FDA )
First Posted: January 13, 2015    Key Record Dates
Last Update Posted: November 6, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue