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SF1126 for Patients With Relapsed or Refractory Neuroblastoma

Primary Purpose

Neuroblastoma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SF1126
Sponsored by
New Approaches to Neuroblastoma Therapy Consortium
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroblastoma

Eligibility Criteria

1 Year - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Children's Hospital Los Angeles
  • UCSF Helen Diller Family Comprehensive Cancer Center
  • Children Hospital of Colorado
  • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
  • University of Chicago Comer Children's Hospital
  • Childrens Hospital Boston, Dana-Farber Cancer Institute.
  • C.S Mott Children's Hospital
  • University of North Carolina
  • Cincinnati Children's Hospital Medical Center
  • Cook Children's Healthcare System
  • Children's Hospital and Regional Medical Center - Seattle

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

SF1126

Arm Description

Patients will receive SF1126 IV over 90 minutes on Days 1 and 4 of each week during each cycle.

Outcomes

Primary Outcome Measures

Toxicities, based on the CTCAE criteria, will be used to measure the severity of adverse events
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

Evaluation of response
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.
Plasma samples will be collected from patients at 9 time points on Day 1 of the first cycle.

Full Information

First Posted
December 18, 2014
Last Updated
August 16, 2018
Sponsor
New Approaches to Neuroblastoma Therapy Consortium
Collaborators
SignalRX Pharmaceuticals, Inc., University of Southern California
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1. Study Identification

Unique Protocol Identification Number
NCT02337309
Brief Title
SF1126 for Patients With Relapsed or Refractory Neuroblastoma
Official Title
Phase I Study of SF1126 for Patients With Relapsed or Refractory Neuroblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Terminated
Why Stopped
Low patient accrual
Study Start Date
July 9, 2015 (Actual)
Primary Completion Date
May 22, 2018 (Actual)
Study Completion Date
May 22, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
New Approaches to Neuroblastoma Therapy Consortium
Collaborators
SignalRX Pharmaceuticals, Inc., University of Southern California

4. Oversight

Data Monitoring Committee
Yes

5. 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SF1126
Arm Type
Other
Arm Description
Patients will receive SF1126 IV over 90 minutes on Days 1 and 4 of each week during each cycle.
Intervention Type
Drug
Intervention Name(s)
SF1126
Intervention Description
SF1126 in IV form with be given to patients on this study.
Primary Outcome Measure Information:
Title
Toxicities, based on the CTCAE criteria, will be used to measure the severity of adverse events
Description
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).
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Evaluation of response
Description
Response will be determined by the evaluation of CT/MRI scans and bone marrow biopsy.
Time Frame
After day 1 of week 4 of cycles 2, 4, and 6
Title
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.
Description
Plasma samples will be collected from patients at 9 time points on Day 1 of the first cycle.
Time Frame
Day 1, cycle 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven DuBois, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027-0700
Country
United States
Facility Name
UCSF Helen Diller Family Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Children Hospital of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Chicago Comer Children's Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Childrens Hospital Boston, Dana-Farber Cancer Institute.
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
C.S Mott Children's Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229-3039
Country
United States
Facility Name
Cook Children's Healthcare System
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Children's Hospital and Regional Medical Center - Seattle
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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SF1126 for Patients With Relapsed or Refractory Neuroblastoma

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