Clinical trial NCT04805333: Phase 1 Dose Escalation of ArtemiCoffee
Official title: A Phase 1 Dose Escalation of ArtemiCoffee in Patients With Advanced Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ovarian Cancer
Keywords: dose escalation
ArtemiCoffee
Artemisia annua
ART-Coffee
herbal
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: ArtemiLife
First posted: 2021-03-18
Enrollment: 13
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase I dose-escalation study of Artemisia annua (Aa) in patients with advanced ovarian cancer who have completed front-line chemotherapy with carboplatin and paclitaxel. The primary objective of this study is to determine the recommended phase II dose (RP2D) of Artemisia annua.

Detailed description: This is a phase I dose-escalation study of Artemisia annua (Aa) decaffeinated coffee in patients with advanced ovarian cancer who have completed front-line chemotherapy with carboplatin and paclitaxel. The primary objective of this study is to determine the recommended phase II dose (RP2D) of Aa decaf coffee pods. Sequential cohorts of three patients per cohort will have escalating doses of Aa, starting with one cup per day (450mg) and with a maximum of 4 cups per day (1800mg). After identifying the RP2D, the study will evaluate an expansion cohort of 6 patients for further tolerability and secondary endpoints. The secondary endpoints include: 1) Efficacy as measured by time to tumor progression or recurrence; 2) the ability of Aa decaf coffee to influence downstream biomarkers of the NRF2/KEAP1 signaling pathway; and 3) plasma concentrations of artemisinin and dihydroartemisinin.

Eligibility criteria: Inclusion Criteria:

* Able to understand and willing to sign a written informed consent document.
* Age ≥ 18 years.
* Patients diagnosed with Stage II-IV ovarian cancer who have completed initial first-line therapy with carboplatin and paclitaxel and achieved a complete response.
* Creatinine clearance ≥ 60 mL/min
* Total bilirubin ≤ 1.5 x ULN, and AST and ALT ≤ 3.0 x ULN
* GOG Performance Status ≤ 2.

Exclusion Criteria:

* 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 visits, in the opinion of the treating physician.
* Pregnant women are excluded from this study.
* Concurrent use of strong inducers of CYP2A6, including phenobarbital and rifampin
* Women with active gastric ulcers are excluded from this study.
* Patients who are receiving concurrent maintenance therapy with a PARP inhibitor for a known hereditary recombinant deficiency (HRD) mutation. Bevacizumab maintenance therapy is allowed.
* Concurrent use of nevirapine, ritonavir and strong UGT inhibitors or inducers.

Primary outcomes:
measure: Recommended Phase II Dose
timeFrame: 150 days
Secondary outcomes:
measure: Progression Free Survival
timeFrame: 150 days
Other outcomes:
measure: Change in plasma concentration of artemisinin.
timeFrame: Up to 150 days (baseline and post-treatment)
measure: Change in plasma concentration of dihydroartemisinin.
timeFrame: Up to 150 days (baseline and post-treatment)
measure: Change in NQ01 expression.
timeFrame: Up to 150 days (baseline and post-treatment)
measure: Change in HO-1 expression.
timeFrame: Up to 150 days (baseline and post-treatment)
measure: Change in ABCF2 expression.
timeFrame: Up to 150 days (baseline and post-treatment)
measure: Change in CD99 expression.
timeFrame: Up to 150 days (baseline and post-treatment)
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Frederick Ueland, MD
role: PRINCIPAL_INVESTIGATOR
References: