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

Pilot Study of NP-101 (TQ Formula) in Combination With Nivolumab and Ipilimumab in Advanced and Metastatic Extra-pulmonary Neuroendocrine Carcinomas (EP-NECAs)

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.

Study Overview

• Status: Recruiting
• Conditions: Neuroendocrine Carcinoma; Gastroenteropancreatic Neuroendocrine Tumor; Gastroenteropancreatic Neuroendocrine Neoplasm; Mixed Neuroendocrine-Non Neuroendocrine Neoplasm
• Intervention / Treatment: Drug: NP-101 (TQ Formula); Drug: Nivolumab (3mg/kg); Drug: Ipilimumab (1mg/kg)

Detailed Description

The purpose of this study is to find out if NP-101 (TQ Formula) given with the immunotherapy drugs called nivolumab and ipilimumab helps with neuroendocrine carcinoma who have progressed on at least one first line standard therapy. NP-101 (TQ Formula) black seed oil tablet is an investigational (experimental) drug that may enhance the effect that immunotherapy drugs such as nivolumab and ipilimumab have on neuroendocrine carcinoma.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Amr Mohamed, MD; Phone Number: 1800-641-2422; Email: Amr.Mohamed@uhhospitals.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
      • Contact: Amr Mohamed, MD; Phone Number: 866-844-2273; Email: Amr.Mohamed@uhhospitals.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

• Subjects of childbearing potential must agree to practice reliable contraception or to practice abstinence for at least 28 days before and for 60 days after the last dose of study drug. Reliable contraception is defined as:

  • One highly effective method and one additional effective (barrier) method:
  • Examples of highly effective methods:
• Intrauterine device (IUD)
• Hormonal (injections, implants, levonorgestrel-releasing intrauterine system [IUS], medroxyprogesterone acetate depot injections, ovulation inhibitory progesterone-only pills [e.g. desogestrel])
• Tubal ligation

• Partner's vasectomy

  • Examples of additional effective methods:
• Male condom
• Diaphragm
• Cervical Cap

Inclusion of Women and minorities

• People of all races and ethnic groups are eligible for this trial.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NP-101 (TQ Formula) + Nivolumab + Ipilimumab

Drug: NP-101 (TQ Formula); 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.; Other Names: Black seed oil capsules; Drug: Nivolumab (3mg/kg); 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.; Other Names: Opdivo; Drug: Ipilimumab (1mg/kg); Intravenously on day 1 of each (21-day) cycle for a total of four cycles only.; Other Names: Yervoy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety profile/toxicity of combining NP-101 (TQ Formula) with nivolumab and ipilimumab.	Number of participants who experience a Grade 3 or greater drug-related adverse events.	Up to 2 years from the start of treatment
Time to progression (TTP)	To determine the time to progression (TTP) using NP-101 (TQ Formula) plus nivolumab and ipilimumab combined regimen in subjects with EP-NECAs	Up to 6 months from the start of treatment

Collaborators and Investigators

• Sponsor: Amr Mohamed MD
• Collaborators: Novatek Pharmaceuticals
• Investigators: Principal Investigator: Amr Mohamed, MD, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2022
• Primary Completion (Estimated): April 15, 2024
• Study Completion (Estimated): April 15, 2024

Study Registration Dates

• First Submitted: February 21, 2022
• First Submitted That Met QC Criteria: March 1, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Extrapulmonary Neuroendocrine Carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasms; Carcinoma; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: CASE5221

Drug and device information, study documents

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