Study of Artesunate in Metastatic Breast Cancer

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.

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)

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