This phase I trial studies whether TQ Formula given with the immunotherapy drugs called nivolumab and ipilimumab helps patients with extrapulmonary neuroendocrine carcinomas (EP-NECAs) that may have spread from where they first started to nearby tissue, lymph nodes, or distant parts of the body (advanced and/or metastatic). TQ formula (black seed oil tablets) may enhance the effect that immunotherapy drugs such as nivolumab and ipilimumab have on neuroendocrine carcinoma. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Experts in neuroendocrine cancer consider these drugs as appropriate treatment for patients whose neuroendocrine cancer did not respond or came back following other treatments.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05262556.
PRIMARY OBJECTIVE:
I. To determine the antitumor activity of black seed oil extract supplement (thymoquinone [TQ formula]) plus nivolumab and ipilimumab in subjects with advanced and/or metastatic EP-NECAs who progressed on first line therapy.
SECONDARY OBJECTIVES:
I. Describe safety profile / toxicity of combining of NP-101 (TQ formula) plus nivolumab and ipilimumab therapy.
II. To determine time to progression (TTP) using this combined regimen in subjects with EP-NECAs.
CORRELATIVE OBJECTIVES:
I. Predictive biomarkers include mismatch repair (MMR) status, and tumor mutation burden (TMB) level through Tempus next generation sequencing (NGS).
II. Protein expression via immunohistochemistry (IHC) including: VEGFR1, VEGFR2, CD34, microvascular density, PGF.
III. Changes in the levels of liquid investigational biomarkers such as sPD-L1, sPD-1, sCD25, sCTLA4, LDH.
IV. Ribonucleic acid (RNA) to measure and compare expression levels of PD-L1, CD4, CD8, CTLA4, by carrying out quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis.
OUTLINE:
Patients receive TQ formula orally (PO) twice daily (BID) on days 1-21, nivolumab intravenously (IV) over 2 hours on day 1, and ipilimumab IV on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 2 hours on day 1 of each cycle. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 3 months for 2 years.
Lead OrganizationCase Comprehensive Cancer Center
Principal InvestigatorAmr Mohamed
