COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

DETECT III - A Multicenter, Phase III Study to Compare Standard Therapy +/- Lapatinib in HER2-ve MBC-Patients With HER2+ve CTCs (DETECT III)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01619111
Recruitment Status : Unknown
Verified June 2017 by Prof. W. Janni, University of Ulm.
Recruitment status was:  Recruiting
First Posted : June 14, 2012
Last Update Posted : June 7, 2017
Information provided by (Responsible Party):
Prof. W. Janni, University of Ulm

Brief Summary:

The HER2 status in breast cancer patients may change during the course of the disease. In 30% of initially HER2-negative patients with circulating tumor cells (CTC), HER2-positive CTCs can be detected in peripheral blood samples(1). At present, it is unclear if therapy based on the HER2 status of CTC offers a clinical benefit for these patients. The DETECT III - trial compares lapatinib, as HER2-targeted therapy in combination with standard therapy versus standard therapy alone in those patients, with initially HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells.

As one of the first interventional trials based on the assessment of CTC phenotypes, the DETECT III - trial aims to evaluate the efficacy of HER2-targeted therapy in patients with MBC and HER2-positive CTCs as well as the significance of CTC as an early predictive marker for treatment response.

Condition or disease Intervention/treatment Phase
HER2-negative Metastatic Breast Cancer HER2-positive Circulating Tumor Cells Drug: standard chemo- or endocrine therapy Drug: standard chemo- or endocrine therapy + Lapatinib Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: DETECT III - A Multicenter, Randomized, Phase III Study to Compare Standard Therapy Alone Versus Standard Therapy Plus Lapatinib in Patients With Initially HER2-negative Metastatic Breast Cancer and HER2-positive Circulating Tumor Cells
Study Start Date : February 2012
Estimated Primary Completion Date : March 2018
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Active Comparator: standard therapy
standard chemo- or endocrine therapy
Drug: standard chemo- or endocrine therapy

standard chemo- or endocrine therapy:

  • Monochemotherapy (containing one of the following): docetaxel, paclitaxel, vinorelbine, capecitabine, NPLD (non-pegylated liposomal doxorubicin)
  • Endocrine therapy: aromatase inhibitors (anastrozole, letrozole, exemestane)

Experimental: standard therapy + lapatinib
standard chemo- or endocrine therapy + lapatinib
Drug: standard chemo- or endocrine therapy + Lapatinib


+ standard chemo- or endocrine therapy:

  • Monochemotherapy (containing one of the following): docetaxel, paclitaxel, vinorelbine, capecitabine, NPLD (non-pegylated liposomal doxorubicin)
  • Endocrine therapy: aromatase inhibitors (anastrozole, letrozole, exemestane)

Primary Outcome Measures :
  1. CTC clearance rate [ Time Frame: 8 - 12 weeks ]
    CTC clearance rate: Proportion of patients with at least one CTC detected in 7.5 ml of peripheral blood drawn before treatment that show no evidence of CTCs in the blood after treatment (CTC prevalence as assessed using the Cell-Search® System; Veridex LLC, Raritan, USA)

Secondary Outcome Measures :
  1. Overall response rate [ Time Frame: 8-12 weeks ]
    Rate of complete (CR) and partial responses (PR) in patients with whom target lesions were defined

  2. Clinical benefit rate [ Time Frame: 8-12 weeks ]
    Rate of patients who were assessed PR or CR or who had stable disease (SD) for at least 6 months.

  3. Overall survival [ Time Frame: 4 weeks ]
    Time from randomization until death of any cause

  4. Dynamic of CTC [ Time Frame: 8-12 weeks ]
    Descriptive statistics of regular CTC counts

  5. Quality of life (QoL) [ Time Frame: 4 weeks ]
    As assessed by evaluation of the EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires.

  6. Safety and tolerability of lapatinib [ Time Frame: 4 weeks ]
    Assessed by evaluation of adverse event (AE) reports.

  7. Intensity of pain [ Time Frame: 4 weeks ]
    Measured by use of numeric rating scale (NRS)

  8. Progression free survival (PFS) [ Time Frame: 8 - 12 weeks ]
    Time interval from randomization until progressive disease (PD) or death from any cause, whichever comes first

  9. Level of compliance to study protocol. [ Time Frame: 4 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Written informed consent in study participation.
  2. Metastatic breast cancer which cannot be treated by surgery or radiotherapy only. The primary tumor and/or biopsies from metastatic sites or locoregional recurrences must have been confirmed as cancer by histopathology. Estrogen Receptor (EG) and Progesterone Receptor (PgR) status must have been documented.
  3. Primary tumor tissue and/or biopsies from metastatic sites or locoregional recurrences were investigated for HER2 status and all of the investigations showed HER2-negativity (i.e.: immunohistochemistry (IHC) score 0-1+ or 2+ and fluorescent in situ hybridization (FISH) negative or just FISH negative, whichever was performed).
  4. Evidence of HER2-positive CTCs. Evidence is assumed if the following holds:

    • At least one CTC could be extracted from 7.5 ml patient blood by means of the CellSearch® Circulating Tumor Cell Kit (Veridex LLC) and
    • At least one of all extracted CTCs was found to be HER2-positive. HER2 status must be assessed by means of IHC or FISH.
  5. Indication for a standard chemo- or endocrine therapy whose combination with lapatinib is either approved (see SPC of Tyverb® 250 mg tablets) or has been investigated in prior clinical trials (see tables of section 8.2.1.).
  6. Tumor evaluation has been performed within 6 weeks before randomization and results are available.
  7. Patients must have at least one lesion that can be accurately measured according to RECIST guideline version 1.1 [Eisenhauer 2009].
  8. Age ≥ 18 years.
  9. ECOG Score < 2
  10. Adequate organ function within 7 days before randomization, evidenced by the following laboratory results below:

    • absolute neutrophil count ≥ 1500/µL,
    • platelet count ≥ 100000/µL,
    • hemoglobin ≥ 9 g/dL,
    • ALT (SGPT) ≤ 2.5 × ULN,
    • AST (SGOT) ≤ 2.5 × ULN,
    • serum alkaline phosphatase ≤ 2.5 × ULN, (Serum alkaline phosphatase may be > 2.5 × ULN only if bone metastases are present and AST (SGOT) and ALT (SGPT) < 1.5× ULN)
    • creatinine ≤ 2.0 mg/dl or 177µmol/L
    • International normalized ratio (INR) and activated partial thromboplastin time or partial thromboplastin time (aPTT or PTT) ≤ 1.5 × ULN Please note: These laboratory criteria only refer to lapatinib therapy; with respect to the standard anticancer therapy the relevant summaries of product characteristics (SPCs) have to be observed additionally.
  11. Left ventricular cardiac ejection fraction (LVEF) ≥ 50%, in case of planned standard chemotherapy with anthracyclines ≥ 55%, and in any case within normal institutional limits as measured by echocardiogram
  12. In case of patients of child bearing potential:

    • Negative pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to randomization,
    • Contraception by means of a reliable method (i.e. non-hormonal contraception, IUD, a double barrier method, vasectomy of the sexual partner, complete sexual abstinence). Patient must consent in maintaining such contraception until 28 days after completion of study treatment.

Exclusion Criteria:

  1. History of hypersensitivity reactions attributed to compounds of similar chemical or biological composition to lapatinib.
  2. History of > 3 chemotherapy lines for metastatic disease (a chemotherapy line being defined as any new chemotherapy and any modification of an existing chemotherapy regimen regardless of the reason for change).
  3. Treatment with investigational agents of any type or anticancer therapy during the trial or within 4 weeks prior to randomization and 6 weeks in case of nitrosoureas or mitomycin C.
  4. Adverse events due to prior anticancer therapy which are > Grade 1 (NCI CTCAE) at time of randomization.
  5. Anti-retroviral therapy due to HIV infection.
  6. Current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
  7. Concurrent disease or condition that might interfere with adequate assessment or evaluation of study data, or any medical disorder that would make the patient's participation unreasonably hazardous.
  8. Other malignant diseases within the last 3 years apart from CIN of the uterine cervix and skin basalioma.
  9. Disease or condition which might restrain the ability to take or absorb oral medication. This includes malabsorption syndrome, requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption (for example resection of small bowel or stomach), uncontrolled inflammatory GI disease (e.g., Crohn's disease) and any other diseases significantly affecting gastrointestinal function as well as inability to swallow and retain oral medication for any other reason.
  10. Active cardiac disease, defined as:

    • History of uncontrolled or symptomatic angina,
    • history of arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation,
    • myocardial infarction less than 6 months from study entry,
    • uncontrolled or symptomatic congestive heart failure,
    • ejection fraction below the institutional normal limit,
    • any other cardiac condition, which in the opinion of the treating physician would make this protocol unreasonably hazardous for the patient.
  11. Dementia, altered mental status, or any psychiatric or social condition which would prohibit the understanding or rendering of informed consent or which might interfere with the patient's adherence to the protocol.
  12. Life expectancy < 3 months.
  13. Male patients.
  14. Pregnancy or nursing.
  15. Primary tumor or biopsies from metastatic sites or locoregional recurrences showing HER2-positivity.
  16. Any prior treatment with anti-HER2 directed therapy.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01619111

Layout table for location contacts
Contact: Susanne Albrecht, MD +49 731 50058520
Contact: Fabienne Schochter, MD +49731 50058520

Layout table for location information
University Hospital Ulm Recruiting
Ulm, Baden-Württemberg, Germany, 89075
Principal Investigator: Wolfgang Janni, MD, PhD         
Sponsors and Collaborators
Prof. W. Janni
Layout table for investigator information
Principal Investigator: Tanja Fehm, MD, PhD Heinrich-Heine University, Duesseldorf
Study Director: Wolfgang Janni, MD, PhD University Hospital Ulm
Additional Information:
Layout table for additonal information
Responsible Party: Prof. W. Janni, Prof. Dr. med. Wolfgang Janni, University of Ulm Identifier: NCT01619111    
Other Study ID Numbers: DETECT III
2010-024238-46 ( EudraCT Number )
First Posted: June 14, 2012    Key Record Dates
Last Update Posted: June 7, 2017
Last Verified: June 2017
Keywords provided by Prof. W. Janni, University of Ulm:
metastatic breast cancer
circulating tumor cells
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplastic Cells, Circulating
Neoplasms by Site
Breast Diseases
Skin Diseases
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action