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Breast CancerPhase 2TAMENDOXNCT03931928

Genotype and Phenotype Guided Supplementation of TAMoxifen Standard Therapy With ENDOXifen in Breast Cancer Patients

A Phase 2 study testing (Z)-Endoxifen supplementation according to genotype and (Z)-Endoxifen supplementation according to plasma levels in people with Breast Cancer and DCIS, run by Robert Bosch Gesellschaft für Medizinische Forschung mbH (RBMF) at 40 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

In hormone-receptor positive breast cancer or DCIS (ductal carcinoma in situ) tamoxifen remains an important treatment option for patients before menopause and those patients after menopause who cannot be treated with aromatase-inhibitors. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer, DCIS
What is being tested?
(Z)-Endoxifen supplementation according to genotype and (Z)-Endoxifen supplementation according to plasma levels
Could I receive a placebo?
No, everyone receives an active treatment
How many people
356 participants
Where
40 sitesGermany
Study dates
10 Sep 2019to 3 May 2021
Phase
Phase 2
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 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent obtained prior to study entry. The patient must be accessible for scheduled visits and treatment.
  • Pre- and postmenopausal women with ductal carcinoma in situ (DCIS) or early stage breast cancer. This includes stage I, IIA, IIB, and IIIA breast cancers.
  • ER+/PR+, ER+/PR- or ER-/PR+ receptor status. Criteria for endocrine sensitivity is ≥1% ER-positive or PR-positive tumor cells on immune-histochemical staining
  • Patients on standard tamoxifen monotherapy (20 mg/d) for at least three months or patients who had switched from AI to tamoxifen who are on tamoxifen treatment for at least three months
  • Age ≥ 18 years
  • Body mass index of 18.5 to 35.0 kg/m2
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  • The Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Absolute neutrophil count greater than or equal to 1 500/µL
  • Platelets greater than or equal to 100 000/µL
  • Total bilirubin within less than or equal to 1.5 times institutional upper limit of normal
  • AST/ALT less than or equal to 2.5 times institutional upper limit of normal
  • The subjects need to be either
  • of non-childbearing potential (documented postmenopausal status, defined as no menses for 12 months without an alternative medical cause, or post hysterectomy, bilateral salpingectomy or bilateral oophorectomy) or
  • of childbearing potential (WOCBP) with negative serum pregnancy test (due to the known reproduction toxicity of tamoxifen found in preclinical studies, WOCBP need to use a highly effective non-hormonal contraception. These are copper IUDs, bilateral tubal ligation, a vasectomized partner (vasectomy at least three months prior to screening) or sexual abstinence. Male or female condoms with/ without spermicide or caps, diaphragms or sponges with spermicide are associated with a failure rate > 1% per year and are thus not sufficient during the intervention period.
  • Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 5.0 Grade ≤ 2 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion)
  • Surgery and radiation therapy of the breast has to be completed upon study entry

Who cannot join

  • Subjects who are unable to understand written and verbal instructions
  • Locally advanced (Stadium IIIB or IIIC) or metastatic (Stage IV) breast cancer at the time of surgery
  • Ongoing chemotherapy and/or treatment with trastuzumab within the last three months; participation in another trial with any investigational/not-marketed drug within 3 months prior to baseline visit
  • Other active second malignancy
  • Invalid result of genotyping
  • Pregnancy
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  • Breast feeding/lactation
  • Oral contraceptives containing estrogens and/or progesterones
  • Pathologic vaginal bleeding in pre-menopausal women or vaginal bleeding in post-menopausal patients
  • Current severe acute somatic or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in judgement of the investigator, would make the patient inappropriate for entry into this study.
  • Severe chronic cardiac or pulmonary disease (heart failure NYHA class 3 and 4), COPD GOLD C or D
  • Chronic or acute renal disease with a glomerular filtration rate < 60 ml/min/1.73 m2, and any patient on peritoneal dialysis or hemodialysis
  • Medical history of thromboembolism (deep vein thrombosis or pulmonary embolism)
  • QTc interval >0.47 sec at screening ECG
  • Concurrent treatment with strong to moderate inhibitors of CYP2D6 which may alter tamoxifen metabolism (Consortium on Breast Cancer Pharmacogenomics 2008):
  • paroxetine, fluoxetine, bupropion, quinidine and duloxetine, diphenhydramine, thioridazine, amiodarone, cimetidine, sertraline
  • Known allergies against an ingredient of the investigational product or tamoxifen

Trial locations and contacts

40 sites in 1 country.

40 sites in 1 country

Germany40 sites

  • Onkologische Gemeinschaftspraxis Brudler-Heinrich-Bangerter Augsburg

    Augsburg, Halderstraße 29, 86150

  • Klinikum am Bruderwald Bamberg, Hämatologie/Internistische Onkologie

    Bamberg, Buger Straße 80, 96049

  • MVZ am Klinikum am Bruderwald Bamberg

    Bamberg, Buger Straße 80, 96049

  • Marienhospital Bottrop, Klinik für Gynäkologie und Geburtshilfe

    Bottrop, Josef-Albers-Straße 70, 46236

  • Evangelisches Diakonie-Krankenhaus Bremen, Frauenklinik

    Bremen, Gröpelinger Heerstraße 406-408, 28239

  • Kliniken der Stadt Köln, Brustzentrum Köln-Holweide

    Cologne, Neufelder Straße 32, 51067

  • St. Johannes Hospital Dortmund, Klinische Forschung

    Dortmund, Johannesstraße 9-17, 44137

  • Onkozentrum Dresden, Fachärzte für Innere Medizin, Hämatologie und Internistische Onkologie

    Dresden, Leipziger Straße 120, 01127

  • Luisenkrankenhaus Düsseldorf GmbH & Co. KG, Brustzentrum

    Düsseldorf, Luise-Rainer-Straße 6-10, 40235

  • MVZ Eggenfelden, Gynäkologische Onkologie

    Eggenfelden, Schellenbruckerstr. 15, 84307

  • Klinikum Esslingen, Klinik für Frauenheilkunde, Brustzentrum

    Esslingen am Neckar, Hirschlandstraße 97, 73730

  • Klinikum Höchst Frankfurt am Main, Klinik für Gynäkologie und Geburtshilfe

    Frankfurt am Main, Gotenstr. 6-8, 65929

  • SRH Wald-Klinikum Gera GmbH, Klinik für Frauenheilkunde/Geburtsmedizin

    Gera, Straße Des Friedens 122, 07548

  • Helios Klinikum Gifhorn, Interdisziplinäres Brustzentrum

    Gifhorn, Campus 6, 38518

  • MVZ am Schlosssee Gifhorn

    Gifhorn, Zur Allerwelle 4, 38518

  • Onkologische Gemeinschaftspraxis Hildesheim, Gynäkologie

    Hildesheim, Bahnhofsplatz 5, 31134

  • ViDiA Christliche Kliniken Karlsruhe, Frauenklinik

    Karlsruhe, Diakonissenstr.28, 76199

  • Städtisches Klinikum Karlsruhe, Frauenklinik

    Karlsruhe, Moltkestr. 90, 76133

  • Elisabeth Krankenhaus Kassel gGmbH, Brustzentrum

    Kassel, Weinbergstr. 7, 34117

  • DRK Kliniken Berlin-Köpenick, Frauenklinik

    Köpenick, Salvador-Allende-Straße 2-8, 12559

  • Klinikum Ludwigsburg, Frauenklinik

    Ludwigsburg, Posilipostraße 4, 71640

  • Klinikum Magdeburg, Klinik für Hämatologie/Onkologie

    Magdeburg, Birkenallee 34, 39130

  • Universitätsfrauenklinik Mainz, Klinik und Poliklinik für Geburtshilfe und Frauenheilkunde

    Mainz, Langenbeckstr. 1, 55131

  • Klinikum Memmingen, Brustzentrum

    Memmingen, Bismarckstraße 23, 87700

  • medius Klinik Ostfildern-Ruit, Brustzentrum

    Ostfildern, Hedelfingerstraße 166, 73760

  • Klinikum Passau, Gynäkologische Onkologie

    Passau, Innstraße 76, 94032

  • Klinikum Quedlinburg, Frauenklinik

    Quedlinburg, Ditfurter Weg 24, 06484

  • Klinikum am Steinenberg Reutlingen, Frauenklinik

    Reutlingen, Steinenbergstr. 31, 72764

  • Gemeinschaftspraxis für Gynäkologie und Geburtshilfe Salzgitter

    Salzgitter, Albert-Schweitzer-Straße 18, 38226

  • SRH Kliniken Sigmaringen, Gynäkologie und Geburtshilfe

    Sigmaringen, Hohenzollerstr. 40, 72488

  • Diakonissen-Krankenhaus Speyer, Klinik für Gynäkologie und Geburtshilfe

    Speyer, Paul-Egell-Straße 33, 67346

  • Johanniter-Krankenhaus Stendal, Klinik für Frauenheilkunde und Geburtshilfe

    Stendal, Bahnhofstr. 24-26, 39576

  • Robert-Bosch-Krankenhaus

    Stuttgart, Auerbachstr. 112, 70376

  • Zentralklinikum Suhl, Klinik für Frauenheilkunde/Geburtsmedizin, Zentrum für klinische Studien

    Suhl, Albert-Schweitzer-Straße 2, 98527

  • Universitätsfrauenklinik Tübingen

    Tübingen, Calwer Straße 7, 72076

  • Harz-Klinikum Wernigerode, Abteilung Gynäkologie und Geburtshilfe

    Wernigerode, Ilsenburger Straße 15, 38855

  • HELIOS Dr. Horst Schmidt Kliniken Wiesbaden, Klinik für Gynäkologie und gyn. Onkologie

    Wiesbaden, Ludwig-Erhard-Straße 100, 65199

  • Rems-Murr-Klinikum-Winnenden, Frauenklinik

    Winnenden, Am Jakobsweg 1, 71364

  • Marienhospital Witten, Brustzentrum

    Witten, Marienplatz 2, 58452

  • Helios Universitätsklinikum Wuppertal GmbH, Brustzentrum

    Wuppertal, Heusnerstraße 40, 42283

Other trials in Germany

About this study

Official title: Genotype and Phenotype Guided Supplementation of TAMoxifen Standard Therapy With ENDOXifen in Breast Cancer Patients (TAMENDOX)

In hormone-receptor positive breast cancer or DCIS (ductal carcinoma in situ) tamoxifen remains an important treatment option for patients before menopause and those patients after menopause who cannot be treated with aromatase-inhibitors. Nonetheless, a considerable amount of patients suffer a relapse of their cancer while on treatment with tamoxifen. Tamoxifen is a drug that is metabolized to a variety of compounds by the human liver, and the most important antihormonally active metabolite is called (Z)-Endoxifen. It is known that patients who have a reduced or absent activity of the drug-metabolizing enzyme CYP2D6 have lower levels of (Z)-Endoxifen. Furthermore, it has been observed that patients on tamoxifen therapy who have absent CYP2D6 activity are at a 2-fold increased risk for disease recurrence, and patients with lower CYP2D6 compared to patients with normal CYP2D6 activity still have a 1.4-fold increased risk for disease recurrence.

This trial will include patients who are already on tamoxifen therapy for at least 3 months and is designed to show that in patients with absent or low CYP2D6 activity, (Z)-Endoxifen supplementation - that is giving (Z)-Endoxifen in addition to tamoxifen for the study period of 42 days - can increase blood levels of (Z)-Endoxifen to therapeutic concentrations. It is planned to included 504 patients in this blinded, randomized trial, which will have a placebo group (receiving no (Z)-Endoxifen) and two intervention groups that will receive 0, 1.5 or 3 mg (Z)-Endoxifen depending on their CYP2D6 genetics or their (Z)-Endoxifen levels at the start of the study.

The trial is not designed to evaluate outcome measures (that is recurrence or survival rates) of (Z)-Endoxifen supplementation in tamoxifen treated patients, but will document the safety of the combined administration of tamoxifen and (Z)-Endoxifen.

Conditions
Breast Cancer, DCIS
Being tested
(Z)-Endoxifen supplementation according to genotype, (Z)-Endoxifen supplementation according to plasma levels
Keywords
tamoxifen, endoxifen, endocrine receptor positive breast cancer, adjuvant therapy
Medical subject headings
Breast Neoplasms, Carcinoma, Intraductal, Noninfiltrating

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • (Z)-Endoxifen supplementation according to genotypeDrug

    Group 2: CYP2D6 genotype predicted intermediate metabolizer receive 1.5 mg, poor metabolizer receive 3 mg (Z)-Endoxifen and extensive or ultrarapid metabolizer receive 0 mg endoxifen (Placebo)

  • (Z)-Endoxifen supplementation according to plasma levelsDrug

    Group 3: Patients will receive (Z)-endoxifen according to (Z)-endoxifen steady state plasma concentrations (phenotype) at screening (i.e. ≤ 15 nM receive 3 mg, > 15 and ≤ 25 nM receive 1.5 mg (Z)-Endoxifen and > 25 nM receive 0 mg (Placebo)

Study groups in NCT03931928
Study groupRoleWhat they receive
Control group (Group 1)No interventionAll patients receive Placebo
Group 2ExperimentalPatients will receive (Z)-endoxifen dosed according to CYP2D6 "genotype"
Receives: Drug: (Z)-Endoxifen supplementation according to genotype
Group 3ExperimentalPatients will receive (Z)-endoxifen dosed according to (Z)-endoxifen steady state plasma concentrations (phenotype) at screening
Receives: Drug: (Z)-Endoxifen supplementation according to plasma levels

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. (Z-)endoxifen plasma concentration > 32 nM

    The primary endpoint is reached if in one or both intervention groups, the proportion of patients with steady state (Z)-endoxifen plasma concentration > 32 nM is greater or equal to the proportion of patients in the control group that reaches steady state (Z)-endoxifen plasma concentration of > 32 nM

    Measured: 42 days (-2 days/+7 days)

Secondary outcomes (2)

  1. Increase in steady state (Z)-endoxifen concentration

    Increase in steady state (Z)-endoxifen concentration from baseline to end of intervention (Visit 3) in patients with or without supplementation of (Z)-endoxifen

    Measured: 42 days (-2 days/+7 days)

  2. Change in steady state plasma concentrations of tamoxifen, desmethyltamoxifen, 4-hydroxytamoxifen and other tamoxifen metabolites following (Z-)endoxifen supplementation

    Assessment of steady state plasma concentrations of tamoxifen, desmethyltamoxifen, 4-hydroxytamoxifen, and other tamoxifen metabolites following (Z)-endoxifen supplementation for 6 weeks

    Measured: 42 days (-2 days/+7 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Apr 2019
  2. Study start10 Sep 2019
  3. Primary completion3 May 2021
  4. Study completion3 May 2021

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
356 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03931928
Sponsor's protocol ID
IKP275 / GBG91
Other IDs
2016-000418-31, 2016
Acronym
TAMENDOX
Status last verified
Sep 2021
First submitted
26 Apr 2019
Last updated
17 Sep 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing (Z)-Endoxifen supplementation according to genotype and (Z)-Endoxifen supplementation according to plasma levels in people with Breast Cancer and DCIS, run by Robert Bosch Gesellschaft für Medizinische Forschung mbH (RBMF) at 40 sites 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 16 inclusion and 17 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 17 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

(Z-)endoxifen plasma concentration > 32 nM (time frame: 42 days (-2 days/+7 days)). 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 NCT03931928.

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 17 Sep 2021.

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