Clinical Trials /

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

NCT01619111

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: DETECT III
  • SECONDARY ID: 2010-024238-46
  • NCT ID: NCT01619111

Conditions

  • HER2-negative Metastatic Breast Cancer
  • HER2-positive Circulating Tumor Cells

Interventions

DrugSynonymsArms
standard chemo- or endocrine therapystandard therapy
standard chemo- or endocrine therapy + Lapatinibstandard therapy + lapatinib

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.

Trial Arms

NameTypeDescriptionInterventions
standard therapyActive Comparatorstandard chemo- or endocrine therapy
  • standard chemo- or endocrine therapy
standard therapy + lapatinibExperimentalstandard chemo- or endocrine therapy + lapatinib
  • standard chemo- or endocrine therapy + Lapatinib

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:CTC clearance rate
Time Frame:8 - 12 weeks
Safety Issue:
Description: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

Measure:Overall response rate
Time Frame:8-12 weeks
Safety Issue:
Description:Rate of complete (CR) and partial responses (PR) in patients with whom target lesions were defined
Measure:Clinical benefit rate
Time Frame:8-12 weeks
Safety Issue:
Description:Rate of patients who were assessed PR or CR or who had stable disease (SD) for at least 6 months.
Measure:Overall survival
Time Frame:4 weeks
Safety Issue:
Description:Time from randomization until death of any cause
Measure:Dynamic of CTC
Time Frame:8-12 weeks
Safety Issue:
Description:Descriptive statistics of regular CTC counts
Measure:Quality of life (QoL)
Time Frame:4 weeks
Safety Issue:
Description:As assessed by evaluation of the EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires.
Measure:Safety and tolerability of lapatinib
Time Frame:4 weeks
Safety Issue:
Description:Assessed by evaluation of adverse event (AE) reports.
Measure:Intensity of pain
Time Frame:4 weeks
Safety Issue:
Description:Measured by use of numeric rating scale (NRS)
Measure:Progression free survival (PFS)
Time Frame:8 - 12 weeks
Safety Issue:
Description:Time interval from randomization until progressive disease (PD) or death from any cause, whichever comes first
Measure:Level of compliance to study protocol.
Time Frame:4 weeks
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Prof. W. Janni

Trial Keywords

  • metastatic breast cancer
  • circulating tumor cells
  • lapatinib

Last Updated

June 6, 2017