Study of Artesunate in Metastatic Breast Cancer

Metastatic Breast Cancer Clinical Trial

— ARTIC-M33/2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00764036
• Other study ID #: M33/2
• Status: Completed
• Phase: Phase 1
• First received: September 30, 2008
• Last updated: July 28, 2017
• Start date: October 2008
• Est. completion date: November 2013

Study information

• Verified date: July 2017
• Source: Heidelberg University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Locally Advanced Breast Cancer
• Metastatic Breast Cancer

Intervention

Drug:
• artesunate
add-on therapy with daily single oral doses of 100, 150 or 200 mg of artesunate

Locations

Country	Name	City	State
Germany	Complementary and Integrative Medicine, Dep. Gyn. Endocrinology, Women's Hospital, University of Heidelberg	Heidelberg	Baden-Württemberg

Sponsors (5)

Lead Sponsor	Collaborator
Heidelberg University	Dafra Pharma, H. W. & J. Hector-Stiftung, Weinheim, HEIFAN-Heidelberger Förderverein d. Ambulanz f. Naturheilkunde eV, Heidelberg, Germany, Monika-Kutzner Stiftung, Berlin, Germany

Country where clinical trial is conducted

Germany, 

References & Publications (5)

Birgersson S, Ericsson T, Blank A, Hagens Cv, Ashton M, Hoffmann KJ. A high-throughput LC-MS/MS assay for quantification of artesunate and its metabolite dihydroartemisinin in human plasma and saliva. Bioanalysis. 2014 Sep;6(18):2357-69. doi: 10.4155/bio.14.116. — View Citation

Ericsson T, Blank A, von Hagens C, Ashton M, Äbelö A. Population pharmacokinetics of artesunate and dihydroartemisinin during long-term oral administration of artesunate to patients with metastatic breast cancer. Eur J Clin Pharmacol. 2014 Dec;70(12):1453 — View Citation

König M, von Hagens C, Hoth S, Baumann I, Walter-Sack I, Edler L, Sertel S. Erratum to: Investigation of ototoxicity of artesunate as add-on therapy in patients with metastatic or locally advanced breast cancer: new audiological results from a prospective — View Citation

König M, von Hagens C, Hoth S, Baumann I, Walter-Sack I, Edler L, Sertel S. Investigation of ototoxicity of artesunate as add-on therapy in patients with metastatic or locally advanced breast cancer: new audiological results from a prospective, open, unco — View Citation

von Hagens C, Walter-Sack I, Goeckenjan M, Osburg J, Storch-Hagenlocher B, Sertel S, Elsässer M, Remppis BA, Edler L, Munzinger J, Efferth T, Schneeweiss A, Strowitzki T. Prospective open uncontrolled phase I study to define a well-tolerated dose of oral — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Further safety data (adverse events) during prolonged treatments latest till the second progression during the add-on therapy with the study medication (compassionate use)		add-on treatments > 4+/- 1 weeks
Other	Collection of further safety data during later individual compassionate use with monitoring if approbriate for the patients' health status		Depending on patients' preference and health status
Primary	Dose limiting adverse events with possible, probable or definite relation with the respective dose level of the add-on therapy		8-12 weeks
Secondary	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