ARTIC-M33/2: Study of Artesunate in Metastatic Breast Cancer

• Sponsor: Heidelberg University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00764036
• Collaborator: Hector-Stiftung (Other), Dafra Pharma (Industry), Monika-Kutzner Stiftung, Berlin, Germany (Other), HEIFAN-Heidelberger Förderverein d. Ambulanz f. Naturheilkunde eV, Heidelberg, Germany (Other)
• Enrollment: 23
• Location: 1
• Arm: 1
• Actual Duration (Months): 61
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer; Locally Advanced Breast Cancer	Drug: artesunate	Phase 1

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)

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Intervention Model: Sequential Assignment
• Intervention Model Description: dose escalationdose escalation
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: experimental arm only add-on therapy with 100, 150 or 200 mg oral artesunate once daily	Drug: artesunate; add-on therapy with daily single oral doses of 100, 150 or 200 mg of artesunate; Other Names: artesunic acid hemisuccinate dihydroqinghaosu hemisuccinate

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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 Outcome Measures

1. 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]

2. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Complementary and Integrative Medicine, Dep. Gyn. Endocrinology, Women's Hospital, University of Heidelberg	Heidelberg	Baden-Württemberg	Germany	D-69120

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Cornelia U v. Hagens, MD, Department of Gynecological Endocrinology and Reproductive Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.

• Responsible Party: Cornelia von Hagens, Head Complementary & Integrative Medicine, Dep. 4.2, Heidelberg University
• ClinicalTrials.gov Identifier: NCT00764036
• Other Study ID Numbers: M33/2
• First Posted: Oct 1, 2008
• Last Update Posted: Aug 1, 2017
• Last Verified: Jul 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Cornelia von Hagens, Head Complementary & Integrative Medicine, Dep. 4.2, Heidelberg University: phase I; safety
• Additional relevant MeSH terms: Breast Neoplasms; Artesunate

Study Results

No Results Posted as of Aug 1, 2017