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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Ulm
Sponsor:
Information provided by (Responsible Party):
Prof. W. Janni, University of Ulm
ClinicalTrials.gov Identifier:
NCT01619111
First received: May 30, 2012
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Ulm:

Primary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: 8-12 weeks ] [ Designated as safety issue: No ]
    Time interval from randomization until progressive disease (PD) or death from any cause, whichever comes first


Secondary Outcome Measures:
  • Overall response rate [ Time Frame: 8-12 weeks ] [ Designated as safety issue: No ]
    Rate of complete (CR) and partial responses (PR) in patients with whom target lesions were defined

  • Clinical benefit rate [ Time Frame: 8-12 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Time from randomization until death of any cause

  • Dynamic of CTC [ Time Frame: 8-12 weeks ] [ Designated as safety issue: No ]
    Descriptive statistics of regular CTC counts

  • Quality of life (QoL) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    As assessed by evaluation of the EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires.

  • Safety and tolerability of lapatinib [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    Assessed by evaluation of adverse event (AE) reports.

  • Intensity of pain [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Measured by use of numeric rating scale (NRS)


Estimated Enrollment: 228
Study Start Date: February 2012
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

    -

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01619111

Contacts
Contact: Susanne Albrecht, MD +49 731 50058520 susanne.albrecht@uniklinik-ulm.de
Contact: Fabienne Schochter, MD +49731 50058520 fabienne.schochter@uniklinik-ulm.de

Locations
Germany
University Hospital Ulm Recruiting
Ulm, Baden-Württemberg, Germany, 89075
Principal Investigator: Wolfgang Janni, MD, PhD         
Sponsors and Collaborators
Prof. W. Janni
Investigators
Principal Investigator: Tanja Fehm, MD, PhD Heinrich-Heine University, Duesseldorf
Study Director: Wolfgang Janni, MD, PhD University Hospital Ulm
  More Information

Additional Information:
Publications:
Responsible Party: Prof. W. Janni, Prof. Dr. med. Wolfgang Janni, University of Ulm
ClinicalTrials.gov Identifier: NCT01619111     History of Changes
Other Study ID Numbers: DETECT III, 2010-024238-46
Study First Received: May 30, 2012
Last Updated: July 30, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Ulm:
metastatic breast cancer
circulating tumor cells
lapatinib

Additional relevant MeSH terms:
Breast Neoplasms
Neoplastic Cells, Circulating
Breast Diseases
Neoplasm Metastasis
Neoplasms
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Skin Diseases
Lapatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014