NP-101 (TQ Formula) With Nivolumab and Ipilimumab in Advanced or Metastatic Extra-pulmonary Neuroendocrine Carcinomas

NCT05262556 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CASE5221
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

A pilot study to evaluate the anti-tumor efficacy of this novel combined regimen (NP-101 TQ Formula plus nivolumab and ipilimumab) in the second-line setting for EP-NECA. NP-101 (TQ Formula) (TQ, C10H12O2) is the main bioactive component of the black seed (Nigella sativa, Ranunculaceae family) and has anti-oxidant, anti-angiogenic effects.

Conditions

Gastroenteropancreatic Neuroendocrine Tumor; Gastroenteropancreatic Neuroendocrine Neoplasm; Neuroendocrine Carcinoma; Mixed Neuroendocrine-Non Neuroendocrine Neoplasm

Keywords

Extrapulmonary Neuroendocrine Carcinoma

Outcome Measures

Primary Outcomes (1)

• Antitumor activity of NP-101 (TQ Formula) plus nivolumab and ipilimumab in subjects with advanced and/or metastatic EP-NECAs who progressed on first line therapy

  Antitumor activity will be measured by the number of participants that have a complete response (CR), partial response (PR), or stable disease (SD). CR is defined as the complete disappearance of all target lesions, confirmed by repeat assessments at no less than 4 weeks after the criteria for response is first met. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameter. SD is defined as neither sufficient decrease to qualify for a partial response nor sufficient increase to qualify for progressive disease.

  Up to 6 months from the start of treatment

Secondary Outcomes (2)

• Safety profile/toxicity of combining NP-101 (TQ Formula) with nivolumab and ipilimumab.

  Up to 2 years from the start of treatment

• Time to progression (TTP)

  Up to 6 months from the start of treatment

Study Arms (1)

NP-101 (TQ Formula) + Nivolumab + Ipilimumab

EXPERIMENTAL

Drug: NP-101 (TQ Formula); Drug: Nivolumab (3mg/kg); Drug: Ipilimumab (1mg/kg)

Interventions

NP-101 (TQ Formula) DRUG

Oral, five 600mg tabs daily every three weeks for four cycles (21-day cycle), then maintenance for an additional 12 weeks for a total of six cycles.

Also known as: Black seed oil capsules

NP-101 (TQ Formula) + Nivolumab + Ipilimumab

Nivolumab (3mg/kg) DRUG

Intravenously on Day 1 every three weeks for four cycles (maximum dose 360mg once every 3 weeks), then 240mg maintenance every two weeks for six cycles for a total of six months of treatment.

Also known as: Opdivo

NP-101 (TQ Formula) + Nivolumab + Ipilimumab

Ipilimumab (1mg/kg) DRUG

Intravenously on day 1 of each (21-day) cycle for a total of four cycles only.

Also known as: Yervoy

NP-101 (TQ Formula) + Nivolumab + Ipilimumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have histologically or cytologically confirmed of relapsed and/or refractory unresectable advanced and/or metastatic high-grade extra-pulmonary neuroendocrine carcinoma (EP-NECAs), and have failed at least one standard line of therapy.
• Subjects must have received at least one prior therapy for this disease. Subjects must have recovered from acute toxicities of prior chemotherapy. Any prior non-hematologic vital organ toxicity (cardiac, pulmonary, hepatic, and renal) of previous therapy must have resolved to grade 1 or less. Neurological toxicities must have resolved to grade 2 or less.
• Age \>18 years.
• Subjects must have radiologic disease measurable by RECIST criteria.
• All previous chemotherapy or radiation must be completed at least three weeks prior to starting study treatment.
• Performance status ECOG Performance status ≤ 2
• Subjects must have normal organ and marrow function as defined below:
• Hemoglobin ≥ 7.0 g/dl
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 75,000/mcL
• Total bilirubin ≤ 3 X institutional upper limit of normal (except subjects with elevated bilirubin unrelated to liver dysfunction)
• AST (SGOT) ≤ 2.5 X institutional upper limit of normal
• ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
• Serum Creatinine ≤ 1.5 X institutional upper limit of normal
• Subjects must have the ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Well-differentiated GEP-NETs are excluded from this trial.
• Prior treatment toxicities that have not resolved to ≤ Grade 2 according to NCI CTCAE Version 5.0 (list exceptions, e.g. alopecia, neuropathy, etc).
• Subjects received prior nivolumab or ipilimumab
• Subjects with untreated brain metastases/CNS disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Participants with treated oligometastatic CNS metastases will be considered for the study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to NP-101 (TQ Formula) or immunotherapy (nivolumab or ipilimumab) used in this study.
• Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or breastfeeding women are excluded from this study because NP-101 (TQ Formula) effects on pregnancy and the fetus used in this protocol is unknown.
• Known chronic active untreated hepatitis B or C infection.
• HIV-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with NP-101 (TQ Formula) and immunotherapy agents.

Sponsors & Collaborators

• Amr Mohamed MD: lead
• Novatek Pharmaceuticals: collaborator

Study Sites (1)

University hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Gastro-enteropancreatic neuroendocrine tumor; Carcinoma, Neuroendocrine

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Amr Mohamed, MD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 21, 2022
• First Posted: March 2, 2022
• Study Start: December 15, 2022
• Primary Completion: December 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: August 7, 2025

Record last verified: 2025-08

Locations

US (1)