Study of NP-101 in Patients With Unresectable Hepatocellular Carcinoma (HCC) Undergoing Y-90 Treatment

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.

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 Overview

• Status: Withdrawn
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: NP-101 (3 g); Drug: NP-101 (4.8 g); Drug: NP-101 (6 g)

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
• 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.

Exclusion Criteria:

• 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.
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NP-101 (3 g)	Drug: 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.
Experimental: NP-101 (4.8 g)	Drug: 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.
Experimental: NP-101 (6 g)	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose	Determine the maximum tolerated dose of NP-101	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	172 weeks

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Florida Department of Health; Novatek
• Investigators: Principal Investigator: Ali Zarrinpar, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: January 10, 2024
• First Submitted That Met QC Criteria: January 10, 2024
• First Posted (Actual): January 22, 2024

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 16, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: hepatocellular carcinoma; Y-90; NP-101
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: UF-GI-018; OCR44171 (Other Identifier: University of Florida); IRB202401248 (Other Identifier: University of Florida)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No