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

NCT01891357 | Terminated Phase 2 Results DMC

• 2 other identifiers: WSG-AM07 (Neo-PREDICT-HER2)2012-003679-21
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Carcinoma, Ductal, Breast

Keywords

Unilateral primary invasive carcinoma of the breast

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR)

  pCR was defined at the time of surgery and measured by size of residual tumor, proportion of vital cells within invasive carcinoma, number of positive lymph nodes (ypN) and size of the largest lymph node metastasis and ductal carcinoma in situ (ypT). pCR is defined as ypT0/is, ypN0. Further exploratory pCR definitions were ypT0, ypN0 (total pCR) and ypT0/is (near pCR).

  Average of 16 weeks

Secondary Outcomes (2)

• Event Free Survival (EFS)

  5-year survival

• Overall Survival (OS)

  5-year survival

Other Outcomes (1)

• Proliferation and Apoptosis Genes

  One week before and after three weeks of treatment

Study Arms (1)

Paclitaxel + Lapatinib + Trastuzumab

EXPERIMENTAL

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; Drug: paclitaxel; Drug: lapatinib; Drug: trastuzumab

Interventions

Biopsy before and after three weeks of study treatment PROCEDURE

Core biopsies for histological analyses, to be analysed by the central pathology

Paclitaxel + Lapatinib + Trastuzumab

paclitaxel DRUG

Paclitaxel + Lapatinib + Trastuzumab

lapatinib DRUG

Paclitaxel + Lapatinib + Trastuzumab

trastuzumab DRUG

Paclitaxel + Lapatinib + Trastuzumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients, age at diagnosis 18 - 75 years
• Histological confirmed unilateral primary invasive carcinoma of the breast
• Clinical Stage Tumor 1 (cT1) (\> 1 cm) - Clinical Stage Tumor 4 (cT4) (if operable, inflammatory breast cancer is excluded)
• 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 \[Fluorescent In-Situ Hybridization (FISH), Chromogenic In-Situ Hybridization (CISH) or Silver In-Situ Hybridization (SISH); \> 6 HER2 gene copies per nucleus or a FISH, CISH or SISH test ratio (HER2 gene copies to chromosome 17 signals) of ≥ 2.0\]
• Clinically node positive disease or node negative disease
• No clinical evidence for distant metastasis (cM0) after conventional staging
• Performance Status Eastern Cooperative Oncology Group (ECOG) ≤ 1 or Karnofsky Index (KI) ≥ 80%
• Baseline Left Ventricular Ejection Fraction (LVEF) \> 50% measured by echocardiography
• Negative pregnancy test (urine or serum) within 7 days prior to start of induction treatment in premenopausal patients
• The patient must be accessible for treatment and follow-up
• 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

You may not qualify if:

• Known hypersensitivity reaction to the compounds or incorporated substances
• Known polyneuropathy grade ≥ 2
• 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).
• Prior malignancy with a disease-free survival of \< 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri
• Prior or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor
• Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry
• Male breast cancer
• Concurrent pregnancy; patients of childbearing potential must implement a highly effective (less than 1% failure rate) non-hormonal contraceptive measures during the study treatment
• Breast feeding women
• Sequential breast cancer
• Lack of patient compliance
• Inadequate organ function including:
• Leucocytes \< 3.5 x 109/l
• Platelets \< 100 x 109/l
• Absolute Neutrophil Count (ANC) \< 1.5 x 109/l

Sponsors & Collaborators

• West German Study Group: lead
• GlaxoSmithKline: collaborator

Study Sites (10)

Klinikum Esslingen

Esslingen am Neckar, Baden-Wurttemberg, 73730, Germany

Location

SLK Kliniken

Heilbronn, Baden-Wurttemberg, 74078, Germany

Location

Klinikum Frankfurt Höchst

Frankfurt am Main, Hesse, 65929, Germany

Location

Niels-Stensen-Kliniken

Georgsmarienhütte, Lower Saxony, 49124, Germany

Location

Krankenhaus Köln Holweide, Brustzentrum

Cologne, North Rhine-Westphalia, 51067, Germany

Location

Klinikum Westfalen GmbH - Knappschaftskrankenhaus

Dortmund, North Rhine-Westphalia, 44309, Germany

Location

Bethesda Krankenhaus, Senologie

Duisburg, North Rhine-Westphalia, 47053, Germany

Location

St. Barbara-KIinik

Hamm, North Rhine-Westphalia, 59073, Germany

Location

Klinikum Chemnitz gGmbH

Chemnitz, Saxony, 09116, Germany

Location

Praxis für gynäkologische Onkologie am Brustzentrum City

Berlin, 10713, Germany

Location

MeSH Terms

Conditions

Carcinoma, Ductal, Breast

Interventions

Pharmaceutical Preparations; Paclitaxel; Lapatinib; Trastuzumab

Condition Hierarchy (Ancestors)

Carcinoma, Ductal; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Ductal, Lobular, and Medullary; Breast Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Only a limited number of core biopsies was available evaluation of dynamic biological changes. Very slow patient recruitment. Negative study results from ALTTO study did no longer justify further conduct.

Results Point of Contact

• Title: Anja Braschoss, Consultant Clinical Research and Medical Writing
• Organization: on behalf of Westdeutsche Studiengruppe GmbH

anja.braschoss@wsg-online.com

0049-176-82119153

Study Officials

• Mathias Warm, MD

  Krankenhaus Köln Holweide

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2013
• First Posted: July 3, 2013
• Study Start: September 30, 2013
• Primary Completion: November 16, 2016
• Study Completion: November 16, 2016
• Last Updated: September 17, 2019
• Results First Posted: September 17, 2019

Record last verified: 2019-09

Locations

DE (10)