Clinical trial NCT02337309: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Neuroblastoma
Lead sponsor: New Approaches to Neuroblastoma Therapy Consortium
Sponsor class: OTHER
Collaborators: name: SignalRX Pharmaceuticals, Inc.
name: University of Southern California
First posted: 2015-01-13
Enrollment: 4
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Toxicities, based on the CTCAE criteria, will be used to measure the severity of adverse events
timeFrame: 6 months
Secondary outcomes:
measure: Evaluation of response
timeFrame: After day 1 of week 4 of cycles 2, 4, and 6
measure: 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.
timeFrame: Day 1, cycle 1
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: Children Hospital of Colorado
state: Colorado
city: Atlanta
country: United States
facility: AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Comer Children's Hospital
state: Illinois
city: Boston
country: United States
facility: Childrens Hospital Boston, Dana-Farber Cancer Institute.
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S Mott Children's Hospital
state: Michigan
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Fort Worth
country: United States
facility: Cook Children's Healthcare System
state: Texas
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Steven DuBois, MD
role: PRINCIPAL_INVESTIGATOR
References: