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

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ClinicalTrials.gov 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
Sponsor:
Information provided by (Responsible Party):
Prof. W. Janni, University of Ulm

Tracking Information
First Submitted Date  ICMJE May 30, 2012
First Posted Date  ICMJE June 14, 2012
Last Update Posted Date June 7, 2017
Study Start Date  ICMJE February 2012
Estimated Primary Completion Date March 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 7, 2015)
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)
Original Primary Outcome Measures  ICMJE
 (submitted: June 12, 2012)
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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2015)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 12, 2012)
  • 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)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE DETECT III - A Multicenter, Phase III Study to Compare Standard Therapy +/- Lapatinib in HER2-ve MBC-Patients With HER2+ve CTCs
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • HER2-negative Metastatic Breast Cancer
  • HER2-positive Circulating Tumor Cells
Intervention  ICMJE
  • 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)
  • Drug: standard chemo- or endocrine therapy + Lapatinib

    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)
Study Arms  ICMJE
  • Active Comparator: standard therapy
    standard chemo- or endocrine therapy
    Intervention: Drug: standard chemo- or endocrine therapy
  • Experimental: standard therapy + lapatinib
    standard chemo- or endocrine therapy + lapatinib
    Intervention: Drug: standard chemo- or endocrine therapy + Lapatinib
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: January 7, 2015)
120
Original Estimated Enrollment  ICMJE
 (submitted: June 12, 2012)
228
Estimated Study Completion Date  ICMJE March 2020
Estimated Primary Completion Date March 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

    -

Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01619111
Other Study ID Numbers  ICMJE DETECT III
2010-024238-46 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Prof. W. Janni, University of Ulm
Study Sponsor  ICMJE Prof. W. Janni
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Tanja Fehm, MD, PhD Heinrich-Heine University, Duesseldorf
Study Director: Wolfgang Janni, MD, PhD University Hospital Ulm
PRS Account University of Ulm
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP