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

NCT01619111 | Completed Phase 3 DMC

• 2 other identifiers: DETECT III2010-024238-46
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

metastatic breast cancer; circulating tumor cells; lapatinib

Outcome Measures

Primary Outcomes (1)

• CTC clearance rate

  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)

  8 - 12 weeks

Secondary Outcomes (9)

• Overall response rate

  8-12 weeks

• Clinical benefit rate

  8-12 weeks

• Overall survival

  4 weeks

• Dynamic of CTC

  8-12 weeks

• Quality of life (QoL)

  4 weeks

Study Arms (2)

standard therapy

ACTIVE COMPARATOR

standard chemo- or endocrine therapy

Drug: standard chemo- or endocrine therapy

standard therapy + lapatinib

EXPERIMENTAL

standard chemo- or endocrine therapy + lapatinib

Drug: standard chemo- or endocrine therapy + Lapatinib

Interventions

standard chemo- or endocrine therapy DRUG

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)

standard therapy

standard chemo- or endocrine therapy + Lapatinib DRUG

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)

standard therapy + lapatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent in study participation.
• 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.
• 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).
• 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.
• 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.).
• Tumor evaluation has been performed within 6 weeks before randomization and results are available.
• Patients must have at least one lesion that can be accurately measured according to RECIST guideline version 1.1 \[Eisenhauer 2009\].
• Age ≥ 18 years.
• ECOG Score \< 2
• 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,

You may not qualify if:

• History of hypersensitivity reactions attributed to compounds of similar chemical or biological composition to lapatinib.
• 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).
• 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.
• Adverse events due to prior anticancer therapy which are \> Grade 1 (NCI CTCAE) at time of randomization.
• Anti-retroviral therapy due to HIV infection.
• 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).
• 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.
• Other malignant diseases within the last 3 years apart from CIN of the uterine cervix and skin basalioma.
• 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.
• 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,

Sponsors & Collaborators

• Prof. Wolfgang Janni: lead

Study Sites (1)

University Hospital Ulm

Ulm, Baden-Wurttemberg, 89075, Germany

Location

Related Publications (2)

• Fehm T, Muller V, Aktas B, Janni W, Schneeweiss A, Stickeler E, Lattrich C, Lohberg 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.

  PMID: 20859679 BACKGROUND

• Fehm T, Mueller V, Banys-Paluchowski M, Fasching PA, Friedl TWP, Hartkopf A, Huober J, Loehberg C, Rack B, Riethdorf S, Schneeweiss A, Wallwiener D, Meier-Stiegen F, Krawczyk N, Jaeger B, Reinhardt F, Hoffmann O, Mueller L, Wimberger P, Ruckhaeberle E, Blohmer JU, Cieslik JP, Franken A, Niederacher D, Neubauer H, Pantel K, Janni W; DETECT Study Group. Efficacy of Lapatinib in Patients with HER2-Negative Metastatic Breast Cancer and HER2-Positive Circulating Tumor Cells-The DETECT III Clinical Trial. Clin Chem. 2024 Jan 4;70(1):307-318. doi: 10.1093/clinchem/hvad144.

  PMID: 38175595 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Breast Neoplasms; Neoplastic Cells, Circulating

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Tanja Fehm, MD, PhD

  Heinrich-Heine University, Duesseldorf

  PRINCIPAL INVESTIGATOR

• Wolfgang Janni, MD, PhD

  University Hospital Ulm

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med. Wolfgang Janni

Study Record Dates

• First Submitted: May 30, 2012
• First Posted: June 14, 2012
• Study Start: February 1, 2012
• Primary Completion: January 1, 2022
• Study Completion: January 1, 2022
• Last Updated: June 4, 2024

Record last verified: 2024-06

Locations

DE (1)