TQ (Thymoquione) Formula With Nivolumab and Ipilimumab in Gastroenteropancreatic Neuroendocrine Carcinomas
Study Details
Study Description
Brief Summary
A pilot study to evaluate the anti-tumor efficacy of this novel combined regimen (TQ Formula plus nivolumab and ipilimumab) in the second-line setting for GEP-NECA. TQ Formula(TQ, C10H12O2) is the main bioactive component of the black seed (Nigella sativa, Ranunculaceae family) and has anti-oxidant, anti-angiogenic effects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
The purpose of this study is to find out if TQ Formula given with the immunotherapy drugs called nivolumab and ipilimumab helps with neuroendocrine carcinoma who have progressed on first line therapy. TQ Formula (black seed oil tablets) is an investigational (experimental) drug that may enhance the effect that immunotherapy drugs such as nivolumab and ipilimumab have on neuroendocrine carcinoma.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TQ Formula + Nivolumab + Ipilimumab
|
Drug: TQ Formula (black seed oil capsules)
-TQ Formula (black seed oil capsules): oral, three 500mg tabs (1500mg) twice a day every three weeks for four cycles (21-day cycle), then maintenance for an additional 12 weeks for a total of six cycles.
Drug: Nivolumab 240 mg
intravenously on day 1 of each (21-day) cycle for a total of four cycles then maintenance every two weeks cycles for a total of six cycles.
Drug: Ipilimumab (1mg/kg)
intravenously on day 1 of each (21-day) cycle for a total of four cycles only.
|
Outcome Measures
Primary Outcome Measures
- Antitumor activity of TQ Formula plus nivolumab and ipilimumab [Up to 6 months from the start of treatment]
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.
Secondary Outcome Measures
- Safety profile of combining TQ Formula with nivolumab and ipilimumab. [Up to 2 years from the start of treatment]
Number of participants who experience a Grade 3 or greater drug-related adverse events.
- Time to progression (TTP) [Up to 6 months from the start of treatment]
To determine the time to progression (TTP) using TQ Formulaplus nivolumab and ipilimumab combined regimen in subjects with GEP-NECAs
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subjects must have histologically or cytologically confirmed of relapsed and/or refractory metastatic high-grade neuroendocrine carcinoma of gastroenteropancreatic origin (GEP-NECAs), or unknown primary with pathology suggestive of GEP origin, and have failed at least one standard line of therapy.
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Subjects must have received first-line prior therapies for this disease with either platinum plus etoposide or irinotecan-based chemotherapy. 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.
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Age >18 years.
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Subjects must have radiologic disease measurable by RECIST criteria.
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All previous chemotherapy or radiation must be completed at least three weeks prior to study entry.
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Performance status ECOG Performance status ≤ 2
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Subjects must have normal organ and marrow function as defined below:
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Hemoglobin ≥ 10.0 g/dl
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Absolute neutrophil count ≥ 1,500/mcL
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Platelet count ≥ 75,000/mcL
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Total bilirubin < 1.5 X institutional upper limit of normal
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AST (SGOT) ≤ 2.5 X institutional upper limit of normal
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ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
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Serum Creatinine < 1.5 X institutional upper limit of normal
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Subjects must have the ability to understand and the willingness to sign a written informed consent document.
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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:
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Intrauterine device (IUD)
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Hormonal (injections, implants, levonorgestrel-releasing intrauterine system [IUS], medroxyprogesterone acetate depot injections, ovulation inhibitory progesterone-only pills [e.g. desogestrel])
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Tubal ligation
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Partner's vasectomy
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Examples of additional effective methods:
-
Male condom
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Diaphragm
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Cervical Cap
Inclusion of Women and minorities
- People of all races and ethnic groups are eligible for this trial.
Exclusion Criteria:
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Well-differentiated GEP-NETs are excluded from this trial.
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Prior treatment toxicities resolved to ≤ Grade 2 according to NCI CTCAE Version 4.0 (list exceptions, e.g. alopecia, neuropathy, etc).
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Subjects received prior Immunotherapy.
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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.
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History of allergic reactions attributed to compounds of similar chemical or biologic composition to TQFormulaor immunotherapy (nivolumab or ipilimumab) used in this study.
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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.
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Pregnant or breastfeeding women are excluded from this study because TQ Formula's effects on pregnancy and the fetus used in this protocol is unknown.
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Chronic active untreated hepatitis B or C infection. (Assessments should include Hepatitis B Surface AB, Hepatitis B Surface AG, Hepatitis B Core AB -Total, Hepatitis B Core AB, IGM, Hepatitis C AB).
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HIV-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with TQFormulaand immunotherapy agents.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University hospitals Seidman Cancer Center, Case Comprehensive Cancer Center | Cleveland | Ohio | United States | 44106 |
Sponsors and Collaborators
- Amr Mohamed MD
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CASE5221