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

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06217094
• Other study ID #: UF-GI-018
• Secondary ID: OCR44171
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: August 2024
• Est. completion date: September 2029

Study information

• Verified date: June 2024
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 18
• Est. completion date: September 2029
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Must provide written informed consent prior to initiating any trial related procedures

• Adults = 18 years of age

• Patient has histologically confirmed hepatocellular carcinoma (HCC) with archived tissue (within the past 6 months) available for study submission or willingness to obtain a diagnostic biopsy.

• Unresectable HCC or not eligible for surgical resection or liver transplantation

• Must have a Child-Turcotte-Pugh score of A or B7

• Patient must be willing to undergo pre- and post- treatment research biopsy to provide a tumor sample for exploratory biomarker research

• 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 = 50,000/mm3

• Serum creatinine = 2.0 mg/dL or 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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Florida	Novatek

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose	Determine the maximum tolerated dose of NP-101	2 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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