NeuroblastomaPhase 1NCT02337309
SF1126 for Patients With Relapsed or Refractory Neuroblastoma
A Phase 1 study testing SF1126 in people with Neuroblastoma, run by New Approaches to Neuroblastoma Therapy Consortium at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 30 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- SF1126
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 11 sitesUnited States
- Study dates
- 9 Jul 2015to 22 May 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
C.S Mott Children's Hospital
Ann Arbor, Michigan, 48109
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
Atlanta, Georgia, 30322
Children Hospital of Colorado
Aurora, Colorado, 80045
Childrens Hospital Boston, Dana-Farber Cancer Institute.
Boston, Massachusetts, 02115
University of North Carolina
Chapel Hill, North Carolina, 27599
University of Chicago Comer Children's Hospital
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
Cook Children's Healthcare System
Fort Worth, Texas, 76104
Children's Hospital Los Angeles
Los Angeles, California, 90027-0700
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94143
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, 98105
About this study
Official title: Phase I Study of SF1126 for Patients With Relapsed or Refractory Neuroblastoma
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
Read the 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.
- Conditions
- Neuroblastoma
- Being tested
- SF1126
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SF1126Drug
SF1126 in IV form with be given to patients on this study.
| Study group | Role | What they receive |
|---|---|---|
| SF1126 | Other | Patients will receive SF1126 IV over 90 minutes on Days 1 and 4 of each week during each cycle. Receives: Drug: SF1126 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 6 months
Secondary outcomes (2)
Evaluation of response
Response will be determined by the evaluation of CT/MRI scans and bone marrow biopsy.
Measured: After day 1 of week 4 of cycles 2, 4, and 6
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.
Measured: Day 1, cycle 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2015 (estimated)
- Study start9 Jul 2015
- Primary completion22 May 2018
- Study completion22 May 2018
Why it stopped: Low patient accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- New Approaches to Neuroblastoma Therapy Consortium
- Sponsor type
- University, hospital or other
- Collaborators
- SignalRX Pharmaceuticals, Inc., University of Southern California
- Responsible party
- Sponsor
- Investigators
- Steven DuBois, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02337309
- Sponsor's protocol ID
- NANT 2014-01
- Other IDs
- N14-01, R01FD005740
- Status last verified
- Aug 2018
- First submitted
- 18 Dec 2014
- Last updated
- 20 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of SF1126 for Patients With Relapsed or Refractory Neuroblastoma
- ClinicalTrials.gov ID
- NCT02337309
- Acronym / sponsor ID
- NANT 2014-01
- Conditions
- Neuroblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low patient accrual
- Enrolment
- 4 participants (actual)
- Lead sponsor
- New Approaches to Neuroblastoma Therapy ConsortiumUniversity, hospital or other
- Collaborators
- SignalRX Pharmaceuticals, Inc., University of Southern California
- Study start
- 9 Jul 2015 (actual)
- Primary completion
- 22 May 2018 (actual)
- Study completion
- 22 May 2018 (actual)
- First posted
- 13 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SF1126 | Other | Drug: SF1126Patients will receive SF1126 IV over 90 minutes on Days 1 and 4 of each week during each cycle. |
Who may qualify
- Ages
- 1 year to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SF1126SF1126 in IV form with be given to patients on this study. | Drug | SF1126 |
Primary outcome
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).
2 secondary outcomes
Evaluation of response
Time frame: After day 1 of week 4 of cycles 2, 4, and 6
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
Results and safety
The study was stopped early (reason given: Low patient accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2018.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven DuBois, MD principal investigator
Dana-Farber Cancer Institute
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SF1126 in people with Neuroblastoma, run by New Approaches to Neuroblastoma Therapy Consortium at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low patient accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicities, based on the CTCAE criteria, will be used to measure the severity of adverse events (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2018.