Phase II Trial to Validate Markers for a Response Evaluation of a Combined Therapy in Patients With HER2+ Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by West German Study Group
Information provided by (Responsible Party):
West German Study Group Identifier:
First received: May 14, 2013
Last updated: August 6, 2015
Last verified: August 2015
The Neo-PREDICT-HER2 Study is phase II trial to validate predictive markers for the response evaluation of a combined chemo-immunotherapy in patients with HER2-positive early breast cancer. The only treatment arm consists of Paclitaxel 80 mg/m2 weekly for 12 weeks with lapatinib 750 mg P.O. daily and trastuzumab 2 mg/kg IV (loading dose 4 mg/kg) weekly for 12 weeks.

Condition Intervention Phase
Carcinoma, Ductal, Breast
Procedure: Biopsy before and after three weeks of study treatment
Drug: Paclitaxel
Drug: lapatinib
Drug: trastuzumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Site, Open Label, Phase II Trial to Validate Predictive Markers for the Response Evaluation of a Combined Chemo-immunotherapy in Patients With HER2-positive Early Breast Cancer

Resource links provided by NLM:

Further study details as provided by West German Study Group:

Primary Outcome Measures:
  • Pathological complete response (pCR) [ Time Frame: Average of 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Event free survival (EFS) [ Time Frame: 5-year survival ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: 5-year survival ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Proliferation and apoptosis genes [ Time Frame: One week before and after three weeks of treatment ] [ Designated as safety issue: No ]
    Proliferation Ki-67, Aurora A Kinase (STK15), survivin, Myb-related protein B (MYBL2),Cyclin B1 and apoptosis genes Bcl2, Epidermal Growth Factor-like 2 (SCUBE2), cleaved caspase C3 will be assessed in the samples from diagnostic and sequential biopsy.

Estimated Enrollment: 80
Study Start Date: June 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Paclitaxel + Lapatinib + Trastuzumab
Paclitaxel 80 mg/m2 weekly for 12 weeks with lapatinib 750 mg P.O. daily and trastuzumab 2 mg/kg IV (loading dose 4 mg/kg) weekly for 12 weeks, biopsy before and after three weeks of study treatment
Procedure: Biopsy before and after three weeks of study treatment
Core biopsies for histological analyses, to be analysed by the central pathology
Drug: Paclitaxel Drug: lapatinib Drug: trastuzumab

Detailed Description:

Trastuzumab (T)-containing neoadjuvant chemotherapy has been reported to increase the probability of pathological complete response (pCR) in HER2 positive disease up to 67 %. Large trials revealed pCR rates (no remaining invasive and in situ components) of about 30-40 %, if anthracyclines/taxane based polychemotherapy was applied or about 40-45 % if no invasive tumor in the breast and lymph nodes was used as a pCR definition.

Nevertheless, resistance to trastuzumab remains one of the most important challenges in adjuvant and metastatic breast cancer therapy causing poor prognosis with an increased incidence of cerebral metastasis and limited therapeutic options after disease progression6. An improvement shows the combination of trastuzumab and lapatinib, which has been reported to have increased efficacy in in-vitro and in metastatic setting in patients who were mostly resistant to both therapies in the previous course of disease. Recent data from the neoadjuvant setting (neoALTTO) - on a paclitaxel backbone - showed a significantly higher pCR rate after L + T than with either compound separately (47 % vs. 20 % and 27.6 % respectively). Several trials are planned to evaluate the combination of both therapies in the adjuvant and neoadjuvant setting.

Clinical response measured by sequential evaluation of different proliferation markers (such as Ki-67) following a course of neoadjuvant chemotherapy has been demonstrated to correlate significantly with an increased risk of relapse in patients not achieving pathological complete response. It is therefore clinically relevant to evaluate such proliferation tools for early prediction of combination therapy efficacy (chemotherapy and HER2 targeted therapy). So far, it remains unclear which method of proliferation measurement is the optimal marker for response evaluation regarding a combined chemo-immunotherapy. However, measurement of proliferation and apoptosis genes as well as assessment of changes in Phosphatidylinositol 3-kinases (PI3K), Protein Kinase B (AKT), Insulin-like Growth Factor (IGF) and stem cell signalling after a short course of therapy could provide a unique signature for a dynamic response evaluation.

The planned trial will validate predictive markers and a dynamic model based on the sequential evaluation of different proliferation and apoptosis markers. Furthermore it will assess the pCR-rate after 12 weeks of therapy. The aim of the study is to define a predictive marker for the response evaluation of a combined chemo-immunotherapy.


Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Female patients, age at diagnosis 18 - 75 years
  2. Histological confirmed unilateral primary invasive carcinoma of the breast
  3. Clinical Stage Tumor 1 (cT1) (> 1 cm) - Clinical Stage Tumor 4 (cT4) (if operable, inflammatory breast cancer is excluded)
  4. HER2 over-expressing tumor confirmed by: 3+ by Immuno-histochemistry (IHC) and/or HER2/neu gene amplification by fluorescence, chromogenic or silver in-situ hybridization [Fluorescent In-Situ Hybridization (FISH), Chromogenic In-Situ Hybridization (CISH) or Silver In-Situ Hybridization (SISH); > 6 HER2 gene copies per nucleus or a FISH, CISH or SISH test ratio (HER2 gene copies to chromosome 17 signals) of ≥ 2.0]
  5. Clinically node positive disease or node negative disease
  6. No clinical evidence for distant metastasis (cM0) after conventional staging
  7. Performance Status Eastern Cooperative Oncology Group (ECOG) ≤ 1 or Karnofsky Index (KI) ≥ 80%
  8. Baseline Left Ventricular Ejection Fraction (LVEF) > 50% measured by echocardiography
  9. Negative pregnancy test (urine or serum) within 7 days prior to start of induction treatment in premenopausal patients
  10. The patient must be accessible for treatment and follow-up
  11. Written informed consent including a written informed consent for shipping of tumor block for central pathology review and evaluation prior to the start of any study procedures

Exclusion Criteria:

  1. Known hypersensitivity reaction to the compounds or incorporated substances
  2. Known polyneuropathy grade ≥ 2
  3. Have acute or currently active or requiring anti-viral therapy hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, stable chronic liver disease per investigator assessment).
  4. Prior malignancy with a disease-free survival of < 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri
  5. Prior or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor
  6. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry
  7. Male breast cancer
  8. Concurrent pregnancy; patients of childbearing potential must implement a highly effective (less than 1% failure rate) non-hormonal contraceptive measures during the study treatment
  9. Breast feeding women
  10. Sequential breast cancer
  11. Lack of patient compliance
  12. Inadequate organ function including:

    • Leucocytes < 3.5 x 109/l
    • Platelets < 100 x 109/l
    • Absolute Neutrophil Count (ANC) < 1.5 x 109/l
    • Hemoglobin < 9 g/dl
    • Serum Creatinine > 1.5 mg/dl
    • Serum Bilirubin > 1.1 mg/dl
    • Alkaline phosphatase > 2.5 x Upper Limit of Normal (ULN)
    • Aspartate Transaminase (ASAT) and/or Alanine Transaminase (ALAT) > 2.5 ULN
    • Albumin < 2.5 g/dl
  13. Uncompensated cardiac function
  14. Malabsorption syndrome, disease significantly affecting gastrointestinal function
  15. Concomitant use of Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers
  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 identifier: NCT01891357

Contact: Mathias Warm, MD +49 221 8907 ext 6707

Klinikum Esslingen Recruiting
Esslingen, Baden-Württemberg, Germany, 73730
Contact: Thorsten Kühn, MD    +49 711 3103 ext 3051      
Contact: Angelika Jursik    +49 711 3103 ext 3064   
Principal Investigator: Thorsten Kühn, MD         
SLK Kliniken Recruiting
Heilbronn, Baden-Württemberg, Germany, 74078
Contact: Reinhard Hackenberg, MD    +49 7131 4934 ext 00      
Principal Investigator: Reinhard Hackenberg, MD         
Klinikum Frankfurt Höchst Recruiting
Frankfurt (Main), Hessen, Germany, 65929
Contact: Volker Möbus, MD    +49 69 3106 ext 2339   
Principal Investigator: Volker Möbus, MD         
Niels-Stensen-Kliniken Recruiting
Georgsmarienhütte, Niedersachsen, Germany, 49124
Contact: Albert von der Assen, MD    +49 541 502 ext 2275      
Principal Investigator: Albert von der Assen, MD         
Klinikum Westfalen GmbH - Knappschaftskrankenhaus Recruiting
Dortmund, Nordrhein-Westfalen, Germany, 44309
Contact: Markus Skrobol, MD         
Contact: Anna Moik    +49 231 9221 ext 078   
Principal Investigator: Markus Skrobol, MD         
Bethesda Krankenhaus, Senologie Recruiting
Duisburg, Nordrhein-Westfalen, Germany, 47053
Contact: Björn Wieland Lisboa, MD    +49 203 6008 ext 1270   
Principal Investigator: Björn Wieland Lisboa, MD         
St. Barbara-KIinik Recruiting
Hamm, Nordrhein-Westfalen, Germany, 59073
Contact: Herrmann Wiebringhaus, MD         
Contact: Scharnewski Christiane    +49 2381 68123 ext 52   
Principal Investigator: Hermann Wiebringhaus, MD         
Krankenhaus Köln Holweide, Brustzentrum Recruiting
Köln, Nordrhein-Westfalen, Germany, 51067
Contact: Mathias Warm, MD    +49 221 8907 ext 6707   
Principal Investigator: Mathias Warm, MD         
Klinikum Chemnitz gGmbH Recruiting
Chemnitz, Sachsen, Germany, 09116
Contact: Nikos Fersis, MD    +49 371 333 ext 22200      
Principal Investigator: Nikos Fersis, MD         
Praxis für gynäkologische Onkologie am Brustzentrum City Recruiting
Berlin, Germany, 10713
Contact: Lidia Perlova-Griff, MD         
Contact: Michaela Platzer    +49 30 8272 ext 29840   
Principal Investigator: Lidia Perlova-Griff, MD         
Sponsors and Collaborators
West German Study Group
Principal Investigator: Mathias Warm, MD Krankenhaus Köln Holweide
  More Information

No publications provided

Responsible Party: West German Study Group Identifier: NCT01891357     History of Changes
Other Study ID Numbers: WSG-AM07 (Neo-PREDICT-HER2), 2012-003679-21
Study First Received: May 14, 2013
Last Updated: August 6, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by West German Study Group:
Unilateral primary invasive carcinoma of the breast

Additional relevant MeSH terms:
Carcinoma, Ductal, Breast
Carcinoma, Ductal
Breast Diseases
Breast Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Ductal, Lobular, and Medullary
Neoplasms, Glandular and Epithelial
Skin Diseases
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses
Tubulin Modulators processed this record on November 27, 2015