Phase 1 Study of SF1126 in Combination With Nivolumab in Patients With Advanced Hepatocellular Carcinoma
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|ClinicalTrials.gov Identifier: NCT03059147|
Recruitment Status : Active, not recruiting
First Posted : February 23, 2017
Last Update Posted : August 14, 2019
- 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.
- 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.
- To describe the safety and tolerability of SF1126 in adult patients with underlying liver disease by ongoing evaluation of adverse events.
- To determine pharmacokinetics in HCC patients.
- To assess the effect of SF1126 in combination with nivolumab on progression-free survival and overall survival.
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.
- Adverse events related to SF1126 (description, timing, grade [CTCAE v4.03], severity, seriousness, and relatedness).
- Pharmacokinetics in HCC patients.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Advanced Hepatocellular Carcinoma||Drug: SF1126 Drug: Nivolumab||Phase 1|
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
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||3 + 3 Designed Phase I study|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||March 27, 2017|
|Actual Primary Completion Date :||April 22, 2019|
|Estimated Study Completion Date :||October 1, 2022|
Experimental: SF1126 + Nivolumab
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.
- Rate of dose limiting toxicities [ Time Frame: Occurring within 56 days of investigational treatment ]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
- Treatment-emergent adverse events [ Time Frame: 3 years ]To describe treatment-emergent adverse events (description, timing, grade [CTCAE v4.03], severity, seriousness, and relatedness)
- Peak plasma concentration (Cmax) [ Time Frame: 3 years ]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
- Area under the plasma concentration versus time curve (AUC) [ Time Frame: 3 years ]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
- Progression-free survival [ Time Frame: 4 months ]The proportion of patients who remain progression free (according to RECIST1.1) after 4 months on study
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03059147
|United States, California|
|UC San Diego Moores Cancer Center|
|La Jolla, California, United States, 92093|