Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00006334

Trial Description

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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

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Trial Acronym

DETECT III

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URL of the Trial

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Brief Summary in Lay Language

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.

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Brief Summary in Scientific Language

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Organizational Data

  •   DRKS00006334
  •   2015/01/21
  •   2012/05/30
  •   yes
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Secondary IDs

  •   2010-024238-46 
  •   NCT01619111  (ClinicalTrials.gov)
  •   DETECT III  (Heinrich-Heine University, Duesseldorf)
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Health Condition or Problem studied

  •   HER2-negative Metastatic Breast Cancer
  •   HER2-positive Circulating Tumor Cells
  •   C50 -  Malignant neoplasm of breast
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Interventions/Observational Groups

  •   Drug: standard chemo- or endocrine therapy
  •   Drug: standard chemo- or endocrine therapy + Lapatinib
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   III
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Primary Outcome

- 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)

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Secondary Outcome

- Overall response rate; time frame: 8-12 weeks; Rate of complete (CR) and partial responses (PR) in patients with whom target lesions were defined
- 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.
- Overall survival; time frame: 4 weeks; Time from randomization until death of any cause
- Dynamic of CTC; time frame: 8-12 weeks; Descriptive statistics of regular CTC counts
- Quality of life (QoL); time frame: 4 weeks; As assessed by evaluation of the EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires.
- Safety and tolerability of lapatinib; time frame: 4 weeks; Assessed by evaluation of adverse event (AE) reports.
- Intensity of pain; time frame: 4 weeks; Measured by use of numeric rating scale (NRS)
- 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
- Level of compliance to study protocol.; time frame: 4 weeks

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  •  
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Recruitment

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  •   2012/02/27
  •   120
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Female
  •   18   Years
  •   no maximum age
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Additional 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.

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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.

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Prof. W. Janni
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    • Heinrich-Heine University, Duesseldorf
    • Tanja Fehm, MD, PhD 
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    • Susanne Albrecht, MD 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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  •   Fehm T, Müller V, Aktas B, Janni W, Schneeweiss A, Stickeler E, Lattrich C, Löhberg CR, Solomayer E, Rack B, Riethdorf S, Klein C, Schindlbeck C, Brocker K, Kasimir-Bauer S, Wallwiener D, Pantel K. HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial. Breast Cancer Res Treat. 2010 Nov;124(2):403-12. doi: 10.1007/s10549-010-1163-x. Epub 2010 Sep 22.; 20859679
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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   5
  •   2017/05/25
* This entry means the parameter is not applicable or has not been set.