Phase 1 Dose Escalation of ArtemiCoffee

Sponsor

Jill M Kolesar (Other)

Overall Status

Recruiting

CT.gov ID

NCT04805333

Collaborator

ArtemiLife (Other)

Enrollment

Location

Arms

21.2

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: Artemisia annua 450mg Drug: Artemisia annua 900mg Drug: Artemisia annua 1350mg Drug: Artemisia annua 1800mg Drug: Artemisia annua - recommended phase II dose	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 26, 2021

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Recommended Phase II Dose [150 days]
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.

Secondary Outcome Measures

Progression Free Survival [150 days]
Median progression free survival will be calculated for all groups.

Other Outcome Measures

Change in plasma concentration of artemisinin. [Up to 150 days (baseline and post-treatment)]
The change in plasma concentration of artemisinin will be measured pre- and post-study.
Change in plasma concentration of dihydroartemisinin. [Up to 150 days (baseline and post-treatment)]
The change in plasma concentration of dihydroartemisinin will be measured pre- and post-study.
Change in NQ01 expression. [Up to 150 days (baseline and post-treatment)]
Change in cell-free (cfRNA) levels of NQ01 (NAD(P)H:quinone oxidoreductase 1) will be measured at baseline and post-treatment.
Change in HO-1 expression. [Up to 150 days (baseline and post-treatment)]
Change in cell-free (cfRNA) levels of HO1 (heme oxygenase 1) will be measured at baseline and post-treatment.
Change in ABCF2 expression. [Up to 150 days (baseline and post-treatment)]
Change in cell-free (cfRNA) levels of HO1 (ATP-binding cassette sub-family F member 2) will be measured at baseline and post-treatment.
Change in CD99 expression. [Up to 150 days (baseline and post-treatment)]
Change in cell-free (cfRNA) levels of CD99 (ATP-binding cassette sub-family F member 2) will be measured at baseline and post-treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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.