Advanced Hepatocellular CarcinomaPhase 1NCT03059147
Phase 1 Study of SF1126 in Combination With Nivolumab in Patients With Advanced Hepatocellular Carcinoma
A Phase 1 study testing SF1126 and Nivolumab in people with Advanced Hepatocellular Carcinoma, run by SignalRX Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Hepatocellular Carcinoma
- What is being tested?
- SF1126 and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Mar 2017to 29 Jun 2020
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To qualify for enrollment, all of the following criteria must be met:
- Willing and able to provide written informed consent prior to performance of any study-specific procedures.
- Age ≥ 18 years.
- Histological or radiologic diagnosis of advanced (unresectable or metastatic) HCC with Child-Pugh A or Child-Pugh B7 cirrhosis:
- The diagnosis of HCC will be made according to the European Association for the Study of the Liver-European Organization for Research and Treatment of Cancer Clinical Practice Guidelines (EASL EASL-EORTC CPG) and according to successive modifications of the American Association for the Study of Liver Disease (AASLD) practice guidelines.
- Pathological diagnoses of HCC will be made according to the International Working Party criteria.
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- Is not a candidate for local therapies, including liver transplantation, tumor ablation, transarterial embolization, or resection.
- No known FDA-approved therapy available that is expected to prolong survival by greater than 3 months.
- ECOG Performance Status ≤ 2.
- Has measurable or evaluable disease as per RECIST v1.1.
- Life expectancy of ≥ 12 weeks.
- Has recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy:
- Myelosuppressive chemotherapy: At least 3 weeks since completion (6 weeks for nitrosourea)
- Biologic (anti-neoplastic agent): At least 7 days since completion of therapy with a biologic agent.
- Radiation (XRT): ≥ 1 week must have elapsed from prior palliative XRT to non-target lesions.
- Inability to tolerate first-line treatment with sorafenib (e.g., unacceptable toxicity), tumor progression on sorafenib, patient preference to stop sorafenib and for alternative therapy/trial, or patient preference to forgo sorafenib for alternative therapy/trial.
- Adequate Bone Marrow Function Defined for all subjects (including status post SCT):
- Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3
- Platelet count ≥ 50,000/mm3
- Hemoglobin ≥ 8.0 g/dL (may receive transfusions)
- Adequate Renal Function Defined As:
- Serum creatinine ≤ 1.5 x institution's ULN (upper limit of normal), or
- Creatinine clearance ≥ 50 ml/min
- Adequate Liver and Pancreatic Function Defined As:
- Total bilirubin ≤ 2.0 x upper limit of normal, and
- ALT or AST ≤ 5 x upper limit of normal, and
- Albumin ≥ 2 g/dL
- Adequate Central Nervous System Function Defined As:
- Subjects with seizure disorder may be enrolled if on anticonvulsants and seizures are well controlled.
- Female subjects are eligible to enter the study if they are either:
- Of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any woman who:
- Has had a hysterectomy, or
- Has had a bilateral oophorectomy, or
- Has had a bilateral tubal ligation, or
- Is post-menopausal (demonstrates total cessation of menses for greater than or equal to 1 year).
- OR
- Of childbearing potential, has a negative serum pregnancy test at screening, and agrees to one of the following contraceptives:
- An intrauterine device (IUD) with a documented failure rate of less than 1% per year.
- Vasectomized partner who is sterile prior to the subject's entry and is the sole sexual partner for that woman.
- Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, during the clinical trial, and for at least 14 days after the last dose of investigational product.
- Double barrier contraception defined as condom with spermicidal jelly, foam, suppository, or film; OR diaphragm with spermicide; OR male condom and diaphragm.
- Male patients with partners of childbearing potential must agree to use adequate contraception while on study
Who cannot join
- Brain metastases or spinal cord compression, unless treatment was completed at least 4 weeks before study entry, and stable without steroid treatment for at least 4 weeks.
- Evidence of severe or uncontrolled systemic diseases [e.g., unstable or uncompensated respiratory, cardiac (including life threatening arrhythmias)].
- Unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy except alopecia (if applicable) unless agreed that the patient can be entered after discussion with the Medical Monitor.
- Presence of cardiac impairment defined as:
- QTc prolongation defined as QTc ≥ 480 ms by ECGs; OR
- prior history of cardiovascular disease including heart failure that meets New York Hearth Association (NYHA) class III and IV definitions; OR
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- history of myocardial infarction/active ischemic heart disease within one year of study entry; OR
- uncontrolled dysrhythmias; OR
- poorly controlled angina.
- Participation in a trial of an investigational agent within the prior 30 days.
- Pregnant or breast-feeding females.
- High volume peritoneal or pleural effusions requiring a tap more frequently than every 14 days. Moderate to severe ascites.
- Poorly controlled or refractory (grade 3-4) hepatic encephalopathy.
- History of other malignancies except curatively excised carcinoma in situ of the cervix, non-melanoma skin cancer or superficial bladder cancer or other solid tumors curatively treated with no evidence of disease for ≥ 5 years. Other cases will be reviewed and possibly allowed if discussed with and approved by Medical Monitor.
- Patients receiving therapeutic doses of warfarin. Lovenox is permitted.
- Criteria for hypertension: Blood pressure greater than 170/90 or 2 SD from normal based on age and weight nomogram on 3 separate measurements. Uncontrolled HTN.
- Any concurrent condition which in the investigator's opinion makes it undesirable for the subject to participate in this trial or which would jeopardize compliance with the protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
UC San Diego Moores Cancer Center
La Jolla, California, 92093
About this study
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
Primary Objectives:
- 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.
Read more
Secondary Objectives:
- 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.
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:
- 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.
Read the detailed description
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
- Conditions
- Advanced Hepatocellular Carcinoma
- Being tested
- SF1126, Nivolumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SF1126Drug
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.
NivolumabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| SF1126 + Nivolumab | Experimental | SF1126 900-1100 mg/m2 IV twice weekly + Nivolumab 240 mg IV every 2 weeks Receives: Drug: SF1126; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of dose limiting toxicities
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
Measured: Occurring within 56 days of investigational treatment
Secondary outcomes (4)
Treatment-emergent adverse events
To describe treatment-emergent adverse events (description, timing, grade [CTCAE v4.03], severity, seriousness, and relatedness)
Measured: 3 years
Peak plasma concentration (Cmax)
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
Measured: 3 years
Area under the plasma concentration versus time curve (AUC)
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
Measured: 3 years
Progression-free survival
The proportion of patients who remain progression free (according to RECIST1.1) after 4 months on study
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2017
- Study start27 Mar 2017
- Primary completion22 Apr 2019
- Study completion29 Jun 2020
Why it stopped: Lack of recruitment and sponsor's priority changes
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Hepatocellular CarcinomaStudies 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
- Model description
- 3 + 3 Designed Phase I study
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- SignalRX Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of California, San Diego
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03059147
- Sponsor's protocol ID
- 161007
- Other IDs
- FD-05113
- Status last verified
- May 2022
- First submitted
- 10 Feb 2017
- Last updated
- 18 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lucibello G, Mograbi B, Milano G, Hofman P, Brest P. PD-L1 regulation revisited: impact on immunotherapeutic strategies. Trends Mol Med. 2021 Sep;27(9):868-881. doi: 10.1016/j.molmed.2021.06.005. Epub 2021 Jun 26.
PubMed 34187739
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03059147
- Acronym / sponsor ID
- 161007
- Conditions
- Advanced Hepatocellular Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of recruitment and sponsor's priority changes
- Enrolment
- 7 participants (actual)
- Lead sponsor
- SignalRX Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- University of California, San Diego
- Study start
- 27 Mar 2017 (actual)
- Primary completion
- 22 Apr 2019 (actual)
- Study completion
- 29 Jun 2020 (actual)
- First posted
- 23 Feb 2017 (actual)
- 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.
Primary Objectives:
- 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.
Secondary Objectives:
- 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.
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:
- 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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 3 + 3 Designed Phase I study
| Arm | Type | Receives |
|---|---|---|
| SF1126 + Nivolumab | Experimental | Drug: SF1126, Drug: NivolumabSF1126 900-1100 mg/m2 IV twice weekly + Nivolumab 240 mg IV every 2 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (42 listed)
- Willing and able to provide written informed consent prior to performance of any study-specific procedures.
- Age ≥ 18 years.
- Histological or radiologic diagnosis of advanced (unresectable or metastatic) HCC with Child-Pugh A or Child-Pugh B7 cirrhosis:
- Is not a candidate for local therapies, including liver transplantation, tumor ablation, transarterial embolization, or resection.
- No known FDA-approved therapy available that is expected to prolong survival by greater than 3 months.
Key exclusion criteria (17 listed)
- Brain metastases or spinal cord compression, unless treatment was completed at least 4 weeks before study entry, and stable without steroid treatment for at least 4 weeks.
- Evidence of severe or uncontrolled systemic diseases [e.g., unstable or uncompensated respiratory, cardiac (including life threatening arrhythmias)].
- Unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy except alopecia (if applicable) unless agreed that the patient can be entered after discussion with the Medical Monitor.
- Presence of cardiac impairment defined as:
- Participation in a trial of an investigational agent within the prior 30 days.
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 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. | Drug | SF1126 + Nivolumab |
| NivolumabNivolumab 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. | Drug | SF1126 + Nivolumab |
Primary outcome
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
4 secondary outcomes
Treatment-emergent adverse events
Time frame: 3 years
Peak plasma concentration (Cmax)
Time frame: 3 years
Area under the plasma concentration versus time curve (AUC)
Time frame: 3 years
Progression-free survival
Time frame: 4 months
Results and safety
The study was stopped early (reason given: Lack of recruitment and sponsor's priority changes). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2022.
- Derived from this study: PubMed 34187739Lucibello G, Mograbi B, Milano G, Hofman P, Brest P. PD-L1 regulation revisited: impact on immunotherapeutic strategies. Trends Mol Med. 2021 Sep;27(9):868-881. doi: 10.1016/j.molmed.2021.06.005. Epub 2021 Jun 26.
- SignalRx Pharmaceuticals websiteLink provided by the sponsor.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site 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 and Nivolumab in people with Advanced Hepatocellular Carcinoma, run by SignalRX Pharmaceuticals, Inc. at 1 site 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 42 inclusion and 17 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 18 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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: Lack of recruitment and sponsor's priority changes). 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?
Rate of dose limiting toxicities (time frame: Occurring within 56 days of investigational treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03059147, which also lists 1 linked publication.
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 18 May 2022; AzTrials last refreshed its copy on 7 Nov 2026.