Metastatic Breast CancerPhase 1ARTIC-M33/2NCT00764036
Study of Artesunate in Metastatic Breast Cancer
A Phase 1 study testing artesunate in people with Metastatic Breast Cancer and Locally Advanced Breast Cancer, run by Heidelberg University at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 to 99 years, women only
- Conditions the study is for
- Metastatic Breast Cancer, Locally Advanced Breast Cancer
- What is being tested?
- artesunate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteGermany
- Study dates
- Oct 2008to Nov 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Compliance for further intake and follow-up expected
- 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
Who cannot join
- 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
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- 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
- 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
- Intolerable health risks by re-exposition with the study medication
Trial locations and contacts
1 site in 1 country.
Germany1 site
Complementary and Integrative Medicine, Dep. Gyn. Endocrinology, Women's Hospital, University of Heidelberg
Heidelberg, Baden-Wurttemberg, D-69120
About this study
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
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.
Read the 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)
- Being tested
- artesunate
- Keywords
- phase I, safety
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
artesunateDrug
Also called artesunic acid hemisuccinate, dihydroqinghaosu hemisuccinate
add-on therapy with daily single oral doses of 100, 150 or 200 mg of artesunate
| Study group | Role | What they receive |
|---|---|---|
| experimental arm only | Experimental | add-on therapy with 100, 150 or 200 mg oral artesunate once daily Receives: Drug: artesunate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting adverse events with possible, probable or definite relation with the respective dose level of the add-on therapy
Measured: 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
Measured: 8-12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2008 (estimated)
- Study startOct 2008
- Primary completionNov 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Model description
- dose escalation
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Heidelberg University
- Sponsor type
- University, hospital or other
- Collaborators
- Hector-Stiftung, Dafra Pharma, Monika-Kutzner Stiftung, Berlin, Germany, HEIFAN-Heidelberger Förderverein d. Ambulanz f. Naturheilkunde eV, Heidelberg, Germany
- Responsible party
- Principal investigator, Cornelia von Hagens, Heidelberg University
- Investigators
- Cornelia U v. Hagens, MD, Principal investigator, Department of Gynecological Endocrinology and Reproductive Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00764036
- Sponsor's protocol ID
- M33/2
- Acronym
- ARTIC-M33/2
- Status last verified
- Jul 2017
- First submitted
- 30 Sep 2008
- Last updated
- 1 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 25384589von 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.
PubMed 28439738Konig 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.
PubMed 26793976Konig 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.
PubMed 27094900Ericsson 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.
PubMed 25248945
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00764036
- Acronym / sponsor ID
- ARTIC-M33/2 / M33/2
- Keywords
- phase I, safety
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Heidelberg UniversityUniversity, hospital or other
- Collaborators
- Hector-Stiftung, Dafra Pharma, Monika-Kutzner Stiftung, Berlin, Germany, HEIFAN-Heidelberger Förderverein d. Ambulanz f. Naturheilkunde eV, Heidelberg, Germany
- Study start
- Oct 2008 (actual)
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 1 Oct 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- dose escalation
| Arm | Type | Receives |
|---|---|---|
| experimental arm only | Experimental | Drug: artesunateadd-on therapy with 100, 150 or 200 mg oral artesunate once daily |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| artesunateAlso: artesunic acid hemisuccinate, dihydroqinghaosu hemisuccinateadd-on therapy with daily single oral doses of 100, 150 or 200 mg of artesunate | Drug | experimental arm only |
Primary outcome
Dose limiting adverse events with possible, probable or definite relation with the respective dose level of the add-on therapy
Time frame: 8-12 weeks
1 secondary outcome
Adverse events relation between adverse events and add-on therapy, cortisol profile in saliva, overall response rate, clinical benefit, assessment of patients expectations
Time frame: 8-12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2017.
- Background: PubMed 25384589Birgersson 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.
- Results publication: PubMed 28439738von 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.
- Results publication: PubMed 26793976Konig 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.
- Results publication: PubMed 27094900Konig 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.
- Results publication: PubMed 25248945Ericsson 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cornelia U v. Hagens, MD principal investigator
Department of Gynecological Endocrinology and Reproductive Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing artesunate in people with Metastatic Breast Cancer and Locally Advanced Breast Cancer, run by Heidelberg University at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting adverse events with possible, probable or definite relation with the respective dose level of the add-on therapy (time frame: 8-12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00764036, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2017.