Phase 1 Dose Escalation of ArtemiCoffee

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: Artemisia annua 450mg
* Drug: Artemisia annua 900mg
* Drug: Artemisia annua 1350mg
* Drug: Artemisia annua 1800mg
* Drug: Artemisia annua - recommended phase II dose


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose 1 - 450mg Artemisia annua<br>Participants in this group will consume 1 cup of decaffeinated coffee (450 mg Artemisia annua). | Drug: Artemisia annua 450mg<br>* Artemisia annua will be self-administered via a preparation of decaffeinated coffee.<br>|
| Experimental: Dose 2 - 900mg Artemisia annua<br>Participants in this group will consume 2 cups of decaffeinated coffee (900 mg Artemisia annua). | Drug: Artemisia annua 900mg<br>* Artemisia annua will be self-administered via a preparation of decaffeinated coffee.<br>|
| Experimental: Dose 3 - 1350mg Artemisia annua<br>Participants in this group will consume 3 cups of decaffeinated coffee (1350 mg Artemisia annua). | Drug: Artemisia annua 1350mg<br>* Artemisia annua will be self-administered via a preparation of decaffeinated coffee.<br>|
| Experimental: Dose 5 - 1800mg Artemisia annua<br>Participants in this group will consume 4 cups of decaffeinated coffee (1800 mg Artemisia annua). | Drug: Artemisia annua 1800mg<br>* Artemisia annua will be self-administered via a preparation of decaffeinated coffee.<br>|
| Experimental: Dose Expansion - Recommended Phase II Dose<br>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). | Drug: Artemisia annua - recommended phase II dose<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Median progression free survival will be calculated for all groups. | 150 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dose escalation, ArtemiCoffee, Artemisia annua, ART-Coffee, herbal