Phase 1 Dose Escalation of ArtemiCoffee

Frederick R. Ueland, M.D.

Status and phase: Completed; Phase 1

Conditions: Ovarian Cancer

Treatments: Drug: Artemisia annua 1800mg; Drug: Artemisia annua 1350mg; Drug: Artemisia annua 900mg; Drug: Artemisia annua - recommended phase II dose; Drug: Artemisia annua 450mg

Study type: Interventional

Funder types: Other

Identifiers

NCT04805333

MCC-20-GYN-08

Details and patient eligibility

About

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.

Full 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.

Enrollment: 13 patients

Sex: Female

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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13 participants in 5 patient groups

Dose 1 - 450mg Artemisia annua

Experimental group

Description:

Participants in this group will consume 1 cup of decaffeinated coffee (450 mg Artemisia annua).

Treatment:

Drug: Artemisia annua 450mg

Dose 2 - 900mg Artemisia annua

Experimental group

Description:

Participants in this group will consume 2 cups of decaffeinated coffee (900 mg Artemisia annua).

Treatment:

Drug: Artemisia annua 900mg

Dose 3 - 1350mg Artemisia annua

Experimental group

Description:

Participants in this group will consume 3 cups of decaffeinated coffee (1350 mg Artemisia annua).

Treatment:

Drug: Artemisia annua 1350mg

Dose 5 - 1800mg Artemisia annua

Experimental group

Description:

Participants in this group will consume 4 cups of decaffeinated coffee (1800 mg Artemisia annua).

Treatment:

Drug: Artemisia annua 1800mg

Dose Expansion - Recommended Phase II Dose

Experimental group

Description:

This cohort will be an expansion of 6 patients for further tolerability and secondary endpoints analysis. They will consume the recommended phase II dose (dependent on prior analysis).

Treatment:

Drug: Artemisia annua - recommended phase II dose