Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Dose Escalating with 3+ patients in each cohort

SF1126

Donald L Durden, MD, PhD

The purpose of this study is to evaluate the safety and tolerability of SF1126 in patients with advanced or metastatic tumors by assessing the dose limiting toxicities (DLTs) and defining the maximum tolerated dose given twice per week for 4 weeks and ultimately define a recommended phase II dose.

SF1126 is a conjugate containing a vascular targeted pan-PI3K inhibitor that selectively inhibits all PI3K class I isoforms and other key members of the PI3K superfamily, including mTORC1/2, DNA-PK, PLK-1, CK2, ATM and PIM-1. SF1126 is designed to inhibit both angiogenesis and cell proliferation by targeting and binding to specific integrins such as αγβ3 that are expressed on the surface of new tumor vasculature and within the tumor compartment. In preclinical xenograft models SF1126 has demonstrated broad activity as a single agent; synergy with commonly used chemotherapy agents, targeted agents, and radiation; and has been shown to reverse resistance mediated through the PI3K/PTEN pathway.

A Dose Escalation Study of SF1126, a PI3 Kinase (PI3K) Inhibitor, Given By Intravenous (IV) Infusion in Patients With Solid Tumors

A Phase I Open Label Safety, Pharmacokinetic and Pharmacodynamic Dose Escalation Study of SF1126, A PI3 Kinase (PI3K) Inhibitor, Given Twice Weekly By IV Infusion To Patients With Advanced or Metastatic Tumors

SignalRX Pharmaceuticals, Inc.

Semafore Pharmaceuticals

Rare Diseases

Recurrence

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Metastatic Squamous Neck Cancer With Occult Primary

SF1126 1110 mg/m2 administered intravenously (IV) twice per week (separated by at least three days) for the first four treatment cycles (28 days) and then once weekly for subsequent cycles.

Ezra Cohen, MD

The purpose of this study is to test the good and bad effects of an experimental drug called SF1126. This drug is being tested in patients whose cancer has not been controlled by available standard therapies and who have certain genes in their tumor.

SF1126 is a drug that inhibits a cell protein called phosphatidyl inositol 3 kinase (PI3K). PI3K is part of signaling pathway that tells cancer cells to grow, survive, invade and metastasize. PI3K also has an important role in the development of blood vessels that are required to support tumor growth. SF1126 is being developed by SignalRx Pharmaceuticals, Inc. It is considered an experimental drug because it is not approved by the FDA for any disease treatment.

SignalRx Pharmaceuticals has developed a pan isoform specific PI-3 inhibitor called SF1126 to treat patients with advanced or metastatic cancer. SF1126 is a conjugate that contains two components: SF1101 (the active drug) and SF1174 (an inactive tetrapeptide RGD targeting moiety)

Both components of SF1126 play key roles in the activity of the drug. SF1101 is a selective inhibitor of certain members of the phosphatidyl inositol 3-kinase (PI-3) family and SF1174 binds selectively to receptors known to be present on neovasculature supporting tumors and on some tumor cells themselves. These components result in a drug designed to be both selective in its activity and targeted in its delivery.

This is an open label Phase II study of SF1126 in adult patients with recurrent or refractory advanced SCCHN with PIK3CA mutation. Treatment cycles (28 days) will consist of SF1126 1110 mg/m2 administered intravenously (IV) twice per week (separated by at least three days) for the first four cycles and then once weekly for subsequent cycles.

SF1126 in Recurrent or Progressive SCCHN and Mutations in PIK3CA Gene and/or PI-3 Kinase Pathway Genes

A Phase II Open Label Study of the PI3 Kinase (PI-3) Inhibitor, SF1126, in Patients With Recurrent or Progressive SCCHN and Mutations in PIK3CA Gene and/or PI-3 Kinase Pathway Genes

best response of PR or CR observed within 6 months of enrollment

Ezra Cohen

Professor

SF1126 1110 mg/m2 administered intravenously (IV) twice per week (separated by at least three days) for the first four treatment cycles (28 days) and then once weekly for subsequent cycles.

SF1126

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

To Determine ORR

Number of Participants With Treatment-related Adverse Events

To Assess the Effect of SF1126 on Time to Progression.

To Assess the Effect of SF1126 on Overall Survival.

To Assess Disease-related Patient-reported Outcomes Using the EORTC-QLQ-

Overall Study

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroepithelioma

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

SF1126 in IV form with be given to patients on this study.

Steven DuBois, MD

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

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.

SF1126 for Patients With Relapsed or Refractory Neuroblastoma

Phase I Study of SF1126 for Patients With Relapsed or Refractory Neuroblastoma

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).

Response will be determined by the evaluation of CT/MRI scans and bone marrow biopsy.

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

University of Southern California

New Approaches to Neuroblastoma Therapy Consortium

Digestive System Diseases

Liver Cirrhosis

Carcinoma, Hepatocellular

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

SF1126 900-1100 mg/m2 IV twice weekly + Nivolumab 240 mg IV every 2 weeks

SF1126 is a dual PI3 kinase/BRD4 inhibitor small molecule. It will be administered IV twice weekly (900 mg/m2 starting dose with escalation to 1000 mg/m2 per dose and 1100 mg/m2 per dose) at a dose determined by the cohort the patient is enrolled in until progression or unacceptable toxicity develops.

Nivolumab is a humanized, IgG4 isotype monoclonal antibody that binds to PD-1 and blocks binding of PD-1 to its ligands PD-L1 and PD-L2. It will be administered at 240 mg IV every 2 weeks until progression or unacceptable toxicity develops.

Primary Objectives:

1. To determine the maximum tolerated dose (MTD) or maximum recommended dose of SF1126 in combination with nivolumab in adult patients with advanced (unresectable or metastatic) HCC and Child-Pugh A or Child-Pugh B7 cirrhosis.
2. To determine the recommended phase II dose of SF1126 in combination with nivolumab in patients with advanced (unresectable or metastatic) HCC and Child-Pugh A or Child-Pugh B7 cirrhosis.

Secondary Objectives:

1. To describe the safety and tolerability of SF1126 in adult patients with underlying liver disease by ongoing evaluation of adverse events.
2. To determine pharmacokinetics in HCC patients.
3. To assess the effect of SF1126 in combination with nivolumab on progression-free survival and overall survival.

Primary Endpoint:

The primary endpoint is the rate of dose limiting toxicities (DLTs) at within 56 days of starting treatment, and the maximum tolerated dose or maximum recommended dose of SF1126 in combination with nivolumab.

Secondary Endpoints:

1. Adverse events related to SF1126 (description, timing, grade \[CTCAE v4.03\], severity, seriousness, and relatedness).
2. Pharmacokinetics in HCC patients.
3. The proportion of patients remaining progression-free by radiographic criteria as assessed by RESIST v1.1 at 4 months, and, as available, median progression-free survival and overall survival estimated using the Kaplan-Meier method.

SF1126 is a dual inhibitor of phosphatidylinositol-3-kinase (pan-isoform specific) and bromodomain-containing protein 4 (BRD4) which simultaneously disrupts two key MYC-mediating factors that promote cancer cell growth.

Nivolumab is a humanized, IgG4 isotype monoclonal antibody that binds to PD-1 and blocks binding of PD-1 to its ligands PD-L1 and PD-L2. Nivolumab monotherapy is approved in the US for HCC previously treated with sorafenib.

Funding source: FDA OOPD

Phase 1 Study of SF1126 in Combination With Nivolumab in Patients With Advanced Hepatocellular Carcinoma

A Phase I Study of SF1126, a Dual PI3 Kinase and Bromodomain Inhibitor, in Combination With Nivolumab in Patients With Advanced or Metastatic Hepatocellular Carcinoma and Child-Pugh A-B7 Cirrhosis

A dose limiting toxicity is a clinically significant adverse event (AE) occurring within 56 days of investigational treatment that is considered by the investigator to be possibly, probably, or definitely related to SF1126

To describe treatment-emergent adverse events (description, timing, grade \[CTCAE v4.03\], severity, seriousness, and relatedness)

Collection of plasma samples for SF1126 Cmax studies is required during cycle 1 for all patients during both the dose escalation and expansion cohort phases of the study

Collection of plasma samples for SF1126 AUC studies is required during cycle 1 for all patients during both the dose escalation and expansion cohort phases of the study

The proportion of patients who remain progression free (according to RECIST1.1) after 4 months on study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Dose Escalation Study of SF1126, a PI3 Kinase (PI3K) Inhibitor, Given By Intravenous (IV) Infusion in Patients With Solid Tumors	NCT00907205	Advanced or Met... Cancer Solid Cancers	SF1126	18 Years -	Semafore Pharmaceuticals
SF1126 in Recurrent or Progressive SCCHN and Mutations in PIK3CA Gene and/or PI-3 Kinase Pathway Genes	NCT02644122	Metastatic Squa...	SF1126	18 Years -	University of California, San Diego
SF1126 for Patients With Relapsed or Refractory Neuroblastoma	NCT02337309	Neuroblastoma	SF1126	1 Year - 30 Years	New Approaches to Neuroblastoma Therapy Consortium
SF1126 in Recurrent or Progressive SCCHN and Mutations in PIK3CA Gene and/or PI-3 Kinase Pathway Genes	NCT02644122	Metastatic Squa...	SF1126	18 Years -	University of California, San Diego
Phase 1 Study of SF1126 in Combination With Nivolumab in Patients With Advanced Hepatocellular Carcinoma	NCT03059147	Advanced Hepato...	SF1126 Nivolumab	18 Years -	SignalRX Pharmaceuticals, Inc.

Spots Global Cancer Trial Database for sf1126

Every month we try and update this database with for sf1126 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for sf1126

Every month we try and update this database with for sf1126 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for sf1126 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.