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SF1126 for Patients With Relapsed or Refractory Neuroblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02337309
Recruitment Status : Terminated (Low patient accrual)
First Posted : January 13, 2015
Last Update Posted : August 20, 2018
Sponsor:
Collaborators:
SignalRX Pharmaceuticals, Inc.
University of Southern California
Information provided by (Responsible Party):
New Approaches to Neuroblastoma Therapy Consortium

Tracking Information
First Submitted Date  ICMJE December 18, 2014
First Posted Date  ICMJE January 13, 2015
Last Update Posted Date August 20, 2018
Actual Study Start Date  ICMJE July 9, 2015
Actual Primary Completion Date May 22, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 8, 2015)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2015)
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SF1126 for Patients With Relapsed or Refractory Neuroblastoma
Official Title  ICMJE Phase I Study of SF1126 for Patients With Relapsed or Refractory Neuroblastoma
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

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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neuroblastoma
Intervention  ICMJE Drug: SF1126
SF1126 in IV form with be given to patients on this study.
Study Arms  ICMJE SF1126
Patients will receive SF1126 IV over 90 minutes on Days 1 and 4 of each week during each cycle.
Intervention: Drug: SF1126
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 30, 2018)
4
Original Estimated Enrollment  ICMJE
 (submitted: January 8, 2015)
28
Actual Study Completion Date  ICMJE May 22, 2018
Actual Primary Completion Date May 22, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries Canada
 
Administrative Information
NCT Number  ICMJE NCT02337309
Other Study ID Numbers  ICMJE NANT 2014-01
N14-01 ( Other Identifier: NANT Consortium )
R01FD005740 ( U.S. FDA Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party New Approaches to Neuroblastoma Therapy Consortium
Original Responsible Party Same as current
Current Study Sponsor  ICMJE New Approaches to Neuroblastoma Therapy Consortium
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • SignalRX Pharmaceuticals, Inc.
  • University of Southern California
Investigators  ICMJE
Principal Investigator: Steven DuBois, MD Dana-Farber Cancer Institute
PRS Account New Approaches to Neuroblastoma Therapy Consortium
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP