Hepatocellular CarcinomaPhase 1NCT06217094
Study of NP-101 in Patients With Unresectable Hepatocellular Carcinoma (HCC) Undergoing Y-90 Treatment
A Phase 1 study testing NP-101 (3 g), NP-101 (4.8 g) and NP-101 (6 g) in people with Hepatocellular Carcinoma, run by University of Florida at 1 site in United States.
Trial summary
Surgical resection and liver transplantation are the primary curative treatments for hepatocellular carcinoma (HCC). However, many patients are ineligible for these treatments due to advanced disease, social factors, or limited availability of liver donors. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- NP-101 (3 g), NP-101 (4.8 g) and NP-101 (6 g)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2026to Sep 2030
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must provide written informed consent prior to initiating any trial related procedures
- Adults ≥ 18 years of age
- Patient has histologically or radiographically confirmed HCC. Initial HCC diagnosis during study screening can also be made based on characteristic imaging pattern per the AASLD (American Association for the Study of Liver Diseases) guidelines (https://journals.lww.com/hep/fulltext/2023/12000/aasld_practice_guidance_on_prevention,_diagnosis,.27.aspx). Per AASLD guidelines: "arterial phase hyperenhancement (APHE) and washout on portal venous or delayed phases of contrast-enhanced multiphase CT or MRI are considered radiological hallmarks of HCC given high specificity and positive predictive value in lesions ≥1 cm in size."
- Unresectable HCC or not eligible for surgical resection or liver transplantation at the time of screening.
- At least one untreated target lesion that could be measured in one dimension, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST).
- Must have a Child-Turcotte-Pugh score of Class A (5-6) or B7
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- ECOG of 0 or 1
- Adequate hematologic, renal, and coagulation function, as evidenced by:
- Hemoglobin ≥ 9 g/dL
- Absolute neutrophil count ≥ 1,500/mm3
- Platelet count ≥ 75,000/mm3
- Creatinine clearance ≥ 30 mL/min
- International Normalized Ratio (INR) ≤ 1.5 or prothrombin time ≤ 3 seconds above control
- Total bilirubin level of ≤ 2.0 mg/dL
- Subjects of childbearing potential (SOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 12 weeks after the last dose of study drug to minimize the risk of pregnancy. Prior to study enrollment, subjects of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
- Subjects with partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 12 weeks following the last dose of study drug.
Who cannot join
- Patient has been treated for this malignancy, has another active malignancy, or has had an active malignancy within the last two years.
- Previous treatment with Y90 radioembolization or systemic treatment for HCC.
- Evidence of macrovascular invasion or extrahepatic metastases.
- Patient has fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC where HCC is not the majority histology.
- Patients who experienced recent GI bleeding or intracranial bleeding or stroke in last 12 weeks, or with uncontrolled blood pressure of history of organ rupture or perforation in last 12 weeks.
- Prior liver transplantation.
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- Subjects of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 12 weeks after the last dose of study drug.
- Subjects who are confirmed to be pregnant or breastfeeding.
- History of any other disease, metabolic dysfunction, clinical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician.
- Administration of a vaccine containing live virus within 30 days prior to the first dose of trial treatment. Note: Most flu vaccines are killed viruses, with the exception of the intra-nasal vainer (Flu-Mist) which is an attenuated live virus and therefore prohibited for 30 days prior to first dose. Non-live versions of the COVID vaccine are allowed.
- Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness
- Use of immunosuppressive drugs, such as steroids, and any herbs, which cannot be discontinued prior to study entry
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Study of NP-101 in Patients With Unresectable Hepatocellular Carcinoma (HCC) Undergoing Y-90 Treatment
Surgical resection and liver transplantation are the primary curative treatments for hepatocellular carcinoma (HCC). However, many patients are ineligible for these treatments due to advanced disease, social factors, or limited availability of liver donors. Therefore, for patients with unresectable HCC, locoregional therapies like transarterial radioembolization (TARE with Y90) are considered the next best non-operative option, especially when the cancer remains confined to the liver. Despite the use of these liver-directed therapies, relapse rates and mortality remain high, underscoring the need for new predictive biomarkers and therapeutic targets, including immune modulation.
The rationale behind NP-101 (TQ formula) stems from its immune modulatory properties as a potent drug derived from a natural substance, black seed or Nigella Sativa. Previous studies have demonstrated its immune modulation and anti-cancer effects, showing promise in preclinical models of HCC. In a randomized phase 2 study conducted in Covid patients, NP-101 exhibited safety and significantly increased T effector cells (CD4+ and CD8+ T lymphocytes), resulting in accelerated recovery. The immune modulation effect of NP-101, observed in the Covid study, and its potential to enhance CD4+ and CD8+ T effector lymphocytes can potentially modify the immune microenvironment and improve outcomes in locally advanced HCC patients undergoing Y90 treatment.
Read more
This study will investigate the safety, efficacy and maximum tolerated dose of NP-101 in patients with unresectable hepatocellular carcinoma.
The dosing scheme for NP-101 in this study will follow a Bayesian Optimal Interval design. Based on the target dose-limiting toxicity (DLT) rate of 30% and assuming a 3+3 design, three subjects will be sequentially enrolled at each of the 3 dose levels (beginning with 3g) until at least one DLT occurs.
If no DLTs occur, dosing will be escalated to the next dose level for the next three enrolled subjects. At either of the two dose levels, if 1 DLT occurs, three more subjects will be enrolled at that dose level. If no DLTs occur in these subjects, three more subjects will be enrolled at the next highest dose level. Dosing escalation will be stopped if two or more total DLTs occur at any dose level. The maximum tolerated dose (MTD) will be one dose level below the dose level at which two or more DLTs occurred.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- NP-101 (3 g), NP-101 (4.8 g), NP-101 (6 g)
- Keywords
- hepatocellular carcinoma, NP-101, Y-90
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NP-101 (3 g)Drug
Subjects will be assigned to take 3 g of NP-101 orally once daily for 28 days pre Y-90 treatment.
NP-101 (4.8 g)Drug
Subjects will be assigned to take 4.8 g of NP-101 orally once daily for 28 days pre Y-90 treatment.
NP-101 (6 g)Drug
Subjects will be assigned to take 6 g of NP-101 orally once daily for 28 days pre Y-90 treatment.
| Study group | Role | What they receive |
|---|---|---|
| NP-101 (3 g) | Experimental | Not described Receives: Drug: NP-101 (3 g) |
| NP-101 (4.8 g) | Experimental | Not described Receives: Drug: NP-101 (4.8 g) |
| NP-101 (6 g) | Experimental | Not described Receives: Drug: NP-101 (6 g) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose
Determine the maximum tolerated dose of NP-101
Measured: 2 months
Secondary outcomes (5)
Overall response rate
Determine the overall response rate. Overall response rate is defined as the percentage of participants who have a confirmed complete response or partial response, as determined by mRECIST.
Measured: 20 weeks
Disease control rate
Determine the disease control rate, which is defined as the percentage of participants who have experienced either a complete response, a partial response, or stable disease per mRECIST criteria.
Measured: 20 weeks
Duration of response
Determine the duration of response, which is defined as the the time from the date of first documented response until the date of documented progression per mRECIST or death due to any cause.
Measured: 20 weeks
Progression-free survival
Determine the progression-free survival, which is defined as time between first study treatment and first documentation of disease progression using RECIST criteria, or to death due to any cause, whichever comes first.
Measured: 1 year
Overall survival
Determine the overall survival, which is defined as time between first study treatment and the date of death due to any cause. In the absence of confirmation of death, survival time will be censored at the last date the subject is known to be alive.
Measured: 172 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2024
- Study startFeb 2026 (estimated)
- Primary completionJul 2028 (estimated)
- Study completionSep 2030 (estimated)
Why it stopped: funding terminated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Novatek, Florida Department of Health
- Responsible party
- Sponsor
- Investigators
- Ali Zarrinpar, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06217094
- Sponsor's protocol ID
- UF-GI-018
- Other IDs
- OCR44171, IRB202401248
- Status last verified
- Feb 2026
- First submitted
- 10 Jan 2024
- Last updated
- 18 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of NP-101 in Patients With Unresectable Hepatocellular Carcinoma (HCC) Undergoing Y-90 Treatment
- ClinicalTrials.gov ID
- NCT06217094
- Acronym / sponsor ID
- UF-GI-018
- Conditions
- Hepatocellular Carcinoma
- Keywords
- hepatocellular carcinoma, NP-101, Y-90
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: funding terminated
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Novatek, Florida Department of Health
- Study start
- Feb 2026 (estimated)
- Primary completion
- Jul 2028 (estimated)
- Study completion
- Sep 2030 (estimated)
- First posted
- 22 Jan 2024 (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.
Surgical resection and liver transplantation are the primary curative treatments for hepatocellular carcinoma (HCC). However, many patients are ineligible for these treatments due to advanced disease, social factors, or limited availability of liver donors. Therefore, for patients with unresectable HCC, locoregional therapies like transarterial radioembolization (TARE with Y90) are considered the next best non-operative option, especially when the cancer remains confined to the liver. Despite the use of these liver-directed therapies, relapse rates and mortality remain high, underscoring the need for new predictive biomarkers and therapeutic targets, including immune modulation.
The rationale behind NP-101 (TQ formula) stems from its immune modulatory properties as a potent drug derived from a natural substance, black seed or Nigella Sativa. Previous studies have demonstrated its immune modulation and anti-cancer effects, showing promise in preclinical models of HCC. In a randomized phase 2 study conducted in Covid patients, NP-101 exhibited safety and significantly increased T effector cells (CD4+ and CD8+ T lymphocytes), resulting in accelerated recovery. The immune modulation effect of NP-101, observed in the Covid study, and its potential to enhance CD4+ and CD8+ T effector lymphocytes can potentially modify the immune microenvironment and improve outcomes in locally advanced HCC patients undergoing Y90 treatment.
This study will investigate the safety, efficacy and maximum tolerated dose of NP-101 in patients with unresectable hepatocellular carcinoma.
The dosing scheme for NP-101 in this study will follow a Bayesian Optimal Interval design. Based on the target dose-limiting toxicity (DLT) rate of 30% and assuming a 3+3 design, three subjects will be sequentially enrolled at each of the 3 dose levels (beginning with 3g) until at least one DLT occurs.
If no DLTs occur, dosing will be escalated to the next dose level for the next three enrolled subjects. At either of the two dose levels, if 1 DLT occurs, three more subjects will be enrolled at that dose level. If no DLTs occur in these subjects, three more subjects will be enrolled at the next highest dose level. Dosing escalation will be stopped if two or more total DLTs occur at any dose level. The maximum tolerated dose (MTD) will be one dose level below the dose level at which two or more DLTs occurred.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| NP-101 (3 g) | Experimental | Drug: NP-101 (3 g) |
| NP-101 (4.8 g) | Experimental | Drug: NP-101 (4.8 g) |
| NP-101 (6 g) | Experimental | Drug: NP-101 (6 g) |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Must provide written informed consent prior to initiating any trial related procedures
- Adults ≥ 18 years of age
- Patient has histologically or radiographically confirmed HCC. Initial HCC diagnosis during study screening can also be made based on characteristic imaging pattern per the AASLD (American Association for the Study of Liver Diseases) guidelines (https://journals.lww.com/hep/fulltext/2023/12000/aasld_practice_guidance_on_prevention,_diagnosis,.27.aspx). Per AASLD guidelines: "arterial phase hyperenhancement (APHE) and washout on portal venous or delayed phases of contrast-enhanced multiphase CT or MRI are considered radiological hallmarks of HCC given high specificity and positive predictive value in lesions ≥1 cm in size."
- Unresectable HCC or not eligible for surgical resection or liver transplantation at the time of screening.
- At least one untreated target lesion that could be measured in one dimension, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST).
Key exclusion criteria (12 listed)
- Patient has been treated for this malignancy, has another active malignancy, or has had an active malignancy within the last two years.
- Previous treatment with Y90 radioembolization or systemic treatment for HCC.
- Evidence of macrovascular invasion or extrahepatic metastases.
- Patient has fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC where HCC is not the majority histology.
- Patients who experienced recent GI bleeding or intracranial bleeding or stroke in last 12 weeks, or with uncontrolled blood pressure of history of organ rupture or perforation in last 12 weeks.
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 |
|---|---|---|
| NP-101 (3 g)Subjects will be assigned to take 3 g of NP-101 orally once daily for 28 days pre Y-90 treatment. | Drug | NP-101 (3 g) |
| NP-101 (4.8 g)Subjects will be assigned to take 4.8 g of NP-101 orally once daily for 28 days pre Y-90 treatment. | Drug | NP-101 (4.8 g) |
| NP-101 (6 g)Subjects will be assigned to take 6 g of NP-101 orally once daily for 28 days pre Y-90 treatment. | Drug | NP-101 (6 g) |
Primary outcome
Maximum tolerated dose
Time frame: 2 months
Determine the maximum tolerated dose of NP-101
5 secondary outcomes
Overall response rate
Time frame: 20 weeks
Disease control rate
Time frame: 20 weeks
Duration of response
Time frame: 20 weeks
Progression-free survival
Time frame: 1 year
Overall survival
Time frame: 172 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2026.
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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.
Ali Zarrinpar, MD principal investigator
University of Florida
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 NP-101 (3 g), NP-101 (4.8 g) and NP-101 (6 g) in people with Hepatocellular Carcinoma, run by University of Florida 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 16 inclusion and 12 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: withdrawn, as of the sponsor's last update on 18 Feb 2026. 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 withdrawn before enrolling participants, so there are no results.
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?
Maximum tolerated dose (time frame: 2 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 18 Feb 2026.