Study of Artesunate in Metastatic Breast Cancer

NCT00764036 | Completed Phase 1 DMC

• 1 other identifier: M33/2
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Breast Cancer; Locally Advanced Breast Cancer

Keywords

phase I; safety

Outcome Measures

Primary Outcomes (1)

• Dose limiting adverse events with possible, probable or definite relation with the respective dose level of the add-on therapy

  8-12 weeks

Secondary Outcomes (1)

• 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

Other Outcomes (2)

• 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

• 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

Study Arms (1)

experimental arm only

EXPERIMENTAL

add-on therapy with 100, 150 or 200 mg oral artesunate once daily

Drug: artesunate

Interventions

artesunate DRUG

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

Also known as: artesunic acid hemisuccinate, dihydroqinghaosu hemisuccinate

experimental arm only

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Heidelberg University: lead
• Hector-Stiftung: collaborator
• Dafra Pharma: collaborator
• Monika-Kutzner Stiftung, Berlin, Germany: collaborator
• HEIFAN-Heidelberger Förderverein d. Ambulanz f. Naturheilkunde eV, Heidelberg, Germany: collaborator

Study Sites (1)

Complementary and Integrative Medicine, Dep. Gyn. Endocrinology, Women's Hospital, University of Heidelberg

Heidelberg, Baden-Wurttemberg, D-69120, Germany

Location

Related 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.

  PMID: 25384589 BACKGROUND

• von Hagens C, Walter-Sack I, Goeckenjan M, Osburg J, Storch-Hagenlocher B, Sertel S, Elsasser 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 artesunate as add-on therapy in patients with metastatic breast cancer (ARTIC M33/2). Breast Cancer Res Treat. 2017 Jul;164(2):359-369. doi: 10.1007/s10549-017-4261-1. Epub 2017 Apr 24.

  PMID: 28439738 RESULT

• Konig 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, uncontrolled, monocentric phase I study. Cancer Chemother Pharmacol. 2016 Feb;77(2):413-27. doi: 10.1007/s00280-016-2960-7. Epub 2016 Jan 21.

  PMID: 26793976 RESULT

• Konig 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, open, uncontrolled, monocentric phase I study. Cancer Chemother Pharmacol. 2016 Jun;77(6):1321. doi: 10.1007/s00280-016-3023-9. No abstract available.

  PMID: 27094900 RESULT

• Ericsson T, Blank A, von Hagens C, Ashton M, Abelo 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):1453-63. doi: 10.1007/s00228-014-1754-2. Epub 2014 Sep 25.

  PMID: 25248945 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Artesunate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons

Study Officials

• Cornelia U v. Hagens, MD

  Department of Gynecological Endocrinology and Reproductive Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head Complementary & Integrative Medicine, Dep. 4.2

Model Details: dose escalation

Study Record Dates

• First Submitted: September 30, 2008
• First Posted: October 1, 2008
• Study Start: October 1, 2008
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: August 1, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)