Phase 1 Dose Escalation of ArtemiCoffee

Ovarian Cancer Clinical Trial

Official title:

A Phase 1 Dose Escalation of ArtemiCoffee in Patients With Advanced Ovarian Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04805333
• Other study ID #: MCC-20-GYN-08
• Status: Recruiting
• Phase: Phase 1
• Start date: March 26, 2021
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Artemisia annua 450mg
Artemisia annua will be self-administered via a preparation of decaffeinated coffee.
• Artemisia annua 900mg
Artemisia annua will be self-administered via a preparation of decaffeinated coffee.
• Artemisia annua 1350mg
Artemisia annua will be self-administered via a preparation of decaffeinated coffee.
• Artemisia annua 1800mg
Artemisia annua will be self-administered via a preparation of decaffeinated coffee.
• Artemisia annua - recommended phase II dose
Artemisia annua will be self-administered via a preparation of decaffeinated coffee. The dose for this cohort will be based on analysis of previous cohorts.

Locations

Country	Name	City	State
United States	University of Kentucky	Lexington	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Jill M Kolesar	ArtemiLife

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in plasma concentration of artemisinin.	The change in plasma concentration of artemisinin will be measured pre- and post-study.	Up to 150 days (baseline and post-treatment)
Other	Change in plasma concentration of dihydroartemisinin.	The change in plasma concentration of dihydroartemisinin will be measured pre- and post-study.	Up to 150 days (baseline and post-treatment)
Other	Change in NQ01 expression.	Change in cell-free (cfRNA) levels of NQ01 (NAD(P)H:quinone oxidoreductase 1) will be measured at baseline and post-treatment.	Up to 150 days (baseline and post-treatment)
Other	Change in HO-1 expression.	Change in cell-free (cfRNA) levels of HO1 (heme oxygenase 1) will be measured at baseline and post-treatment.	Up to 150 days (baseline and post-treatment)
Other	Change in ABCF2 expression.	Change in cell-free (cfRNA) levels of HO1 (ATP-binding cassette sub-family F member 2) will be measured at baseline and post-treatment.	Up to 150 days (baseline and post-treatment)
Other	Change in CD99 expression.	Change in cell-free (cfRNA) levels of CD99 (ATP-binding cassette sub-family F member 2) will be measured at baseline and post-treatment.	Up to 150 days (baseline and post-treatment)
Primary	Recommended Phase II Dose	This study will determine the recommended phase II dose of Artemisia annua decaffeinated coffee. Once the dose escalation is finished or 12 patients are evaluated for the dose-limiting toxicity (DLT), the final recommended phase II dose will be determined by isotonic regression to pool the DLT information across all dose levels.	150 days
Secondary	Progression Free Survival	Median progression free survival will be calculated for all groups.	150 days