NP-101 for Liver Cancer

Overseen By Judy Walsh

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Florida

Disqualifiers: Active malignancy, Macrovascular invasion, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

18 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get specific guidance based on your situation.

What safety information is available for NP-101 (nabilone) in humans?

Nabilone, also known as NP-101, has been studied for its safety in humans, particularly in cancer patients undergoing chemotherapy. Common side effects include drowsiness, dizziness, dry mouth, and low blood pressure when standing up. While it is effective in reducing nausea and vomiting, these side effects suggest caution is needed when using it. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Research Team

Ali Zarrinpar, MD

Principal Investigator

University of Florida

Eligibility Criteria

This trial is for adults over 18 with unresectable hepatocellular carcinoma (HCC) who can't have surgery or a liver transplant. They must be in good physical condition, have certain blood cell counts within range, and agree to provide tissue samples for research.

Inclusion Criteria

My liver cancer cannot be removed by surgery or treated with a liver transplant.

I am fully active or can carry out light work.

Your hemoglobin level is at least 9 grams per deciliter.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NP-101 with dose escalation based on a Bayesian Optimal Interval design to determine the maximum tolerated dose

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

20 weeks

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

172 weeks

Treatment Details

Interventions

• NP-101

Trial Overview The study tests different doses of NP-101, an immune-modulating drug derived from black seed, in patients with HCC undergoing Y-90 treatment. It aims to find the highest dose that doesn't cause too many side effects (maximum tolerated dose).

Participant Groups

Group I: NP-101 (6 g) Experimental Treatment 1 Intervention

Group II: NP-101 (4.8 g) Experimental Treatment 1 Intervention

Group III: NP-101 (3 g) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Florida Department of Health

Collaborator

Trials

30

Recruited

13,000+

Novatek

Collaborator

Trials

1

Recruited

20+

References

1. Germany pubmed.ncbi.nlm.nih.gov

Prospective randomized double-blind trial of nabilone versus domperidone in the treatment of cytotoxic-induced emesis. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Nabilone: an effective antiemetic in patients receiving cancer chemotherapy. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Cannabinoids and Cancer Chemotherapy-Associated Adverse Effects. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Concise review of the management of iatrogenic emesis using cannabinoids: emphasis on nabilone for chemotherapy-induced nausea and vomiting. [2018]