Study of Artesunate in Metastatic Breast Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluation the tolerability of an add-on therapy with artesunate with a duration of 4 weeks in patients with advanced breast cancer.

Detailed Description
-----------------
Additional objectives are: parallel sampling of blood and saliva for the determination of drug concentrations and pharmacokinetic parameters in a substudy on the day of first application and during steady state attempt to establish a therapeutical drug monitoring collection of further safety data during prolonged add-on treatments (compassionate use)

Official Title
-----------------
Prospective Open Uncontrolled Phase I Study of Compatibility, Safety&Pharmacokinetics of Artesunate, a Semisynthetic Derivative of Artemisinin From the Chinese Herb Artemisia Annua in Patients With Metastatic/Locally Advanced Breast Cancer

Conditions
-----------------
Metastatic Breast Cancer, Locally Advanced Breast Cancer

Intervention / Treatment
-----------------
* Drug: artesunate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with histologically or cytologically confirmed breast cancer Distant metastases or locally advanced breast cancer Age ≥ 18 years ECOG performance ≤ 2 Life expectancy of at least 6 months Written informed consent individual standard therapy according to guidelines Oral intake of trial medication possible Compliance with study procedures Women of childbearing potential: negative pregnancy test before start of medication Use of a highly effective method of birth control during intake of add-on therapy for women of childbearing potential being sexually active Inclusion Criteria for Extended Treatment Phase: Participant of the phase I study ARTIC M33/2 who had tolerated the study medication for 4±1 weeks without clinically relvant adverse events or after improvement to ≤ grade 2 Participant of the phase I study ARTIC M33/2 with possible benefit by continuation or restart of the add-on therapy after a next progression according to current scientific knowledge Written informed consent for extended treatment phase Consent of the responsible oncologist Compliance for further intake and follow-up expected Inclusion Criteria for Individual Compassionate Use: Participant of the phase I study ARTIC M33/2 Available standard therapies have minimal or only short activity or intolerable side effects Written informed consent for compassionate use Consent of the responsible oncologist Exclusion Criteria: Allergy to artesunate or to other artemisinin derivatives Concurrent conditions interfering with patient safety Communication problems Concurrent participation in another clinical trial or 4 weeks prior to recruitment Participation in a clinical trial with an unapproved drug 6 months prior to recruitment Sinus bradycardia, bradyarrhythmia AV-Block II° and III° QTc > 500 msec Previously known long QT-syndrome Concurrent intake of a medication with clinically relevant neurotoxicity or during 30 days prior to recruitment Relevant neurological symptoms which might complicate the evaluation of the compatibility of the IMPD (f. e. cerebral metastases) or might be subject to worsening during intake of the IMPD Radiotherapy 2 weeks prior of the intake of the IMPD Concurrent intake of supplements or any other medication with unapproved efficacy f.e. vitamins, minerals or others (OTC) Pregnancy and lactation Ineffective mode of contraception in women of childbearing potential Exclusion Criteria for Extended Treatment Phase: Clinically relevant adverse Events during the first 4 weeks of intake of study medication possibly, probably or definitely related to the study medication Intolerable health risks by continuation re-exposition with the study medication Continuation or re-exposition is medically not acceptable after consultation of physicians responsible for their standard therapy Exclusion Criteria for Individual Compassionate Use: - Intolerable health risks by re-exposition with the study medication

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: dose escalation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental arm only<br>add-on therapy with 100, 150 or 200 mg oral artesunate once daily | Drug: artesunate<br>* add-on therapy with daily single oral doses of 100, 150 or 200 mg of artesunate<br>* Other names: dihydroqinghaosu hemisuccinate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting adverse events with possible, probable or definite relation with the respective dose level of the add-on therapy |  | 8-12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events relation between adverse events and add-on therapy, cortisol profile in saliva, overall response rate, clinical benefit, assessment of patients expectations |  | 8-12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
phase I, safety