Imaging for Response Assessment of Neoadjuvant Chemotherapy in Primary Breast Cancer (GALADON)

NCT01690325 | Terminated Phase 2

• 1 other identifier: WSG-AM05
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

The GALADON trial is a diagnostic and interventional study in which different molecular imaging methods as Positon Emission Tomography (PET), different kind of Magnetic Resonance Imaging - methods (MRI, DWI and DCE-MRI) will be compared with common imaging methods (mammography, ultrasound) to see if there can detect an early response to a combined neoadjuvant therapy with bevacizumab and docetaxel in patients with locally advanced breast cancer. Neoadjuvant chemotherapy (this means patients were treated before the tumor was removed by surgery) with a drug like trastuzumab (monoclonal antibody) which is target to the Her2-protein is much more powerful than with chemotherapy alone because it is normalizing the blood supply and improves tumor delivery of conventional chemotherapy like docetaxel. The HER2 protein is only available in about 30 % of breast cancer types. bevacizumab is another humanized monoclonal antibody like trastuzumab but is effective not only in patients with an positive HER2 status and in combination with trastuzumab it may emphasize the effect in reduction of tumor growth. Bevacizumab is approved in advanced disease, but no major neoadjuvant data available so far for primary breast cancer. As the therapy with monoclonal antibody regimes are expensive and may cause severe side effects predictive factors to select patients who will benefit from such highly specific drugs before therapy start would be medically and economically highly valuable. In this study the efficacy of combined neoadjuvant chemotherapy with bevacizumab, trastuzumab and docetaxel in Arm A and bevacizumab and docetaxel in Arm B should be evaluated and the predictive impact of different imaging methods for tumor response should be shown.

Conditions

Breast Cancer

Keywords

Neoadjuvant chemotherapy; Neoadjuvant cytotoxic-antiangiogenic therapy; Bevacizumab; PET

Outcome Measures

Primary Outcomes (1)

• Rate of pathological complete response (pCR) following neoadjuvant therapy in group A and group B

  To determine efficacy of cytotoxic-antiangiogenic neoadjuvant therapy in primary breast cancer: bevacizumab+trastuzumab+docetaxel fro group A (HER2 positive) or bevacizumab+docetaxel for group B (HER2 negative) using pathological complete response (pCR) as the primary endpoint.

  about 18 weeks (start of neoadjuvant chemotherapy until surgery)

Study Arms (2)

Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.

EXPERIMENTAL

Arm A: Neoadjuvant: 6 cycles of Docetaxel every 21 days together with 6 cycles of Avastin and Herceptin; Adjuvant: 4 cycles of Epirubicin and Cyclophosphamid every 21 days together with 12 cycles of Herceptin every 21 days.

Drug: Docetaxel; Drug: Trastuzumab; Drug: Bevacizumab; Drug: Epirubicin; Drug: Cyclophosphamid

Docetaxel, Avastin; adjuvant Epirubicin, Cyclophosphamid

EXPERIMENTAL

Arm B: neoadjuvant: 6 cycles of Docetaxel and Avastin every 21 days. Adjuvant: 4 cycles of Epirubicin and Cyclophosphamid every 21 days.

Drug: Docetaxel; Drug: Bevacizumab; Drug: Epirubicin; Drug: Cyclophosphamid

Interventions

Docetaxel DRUG

Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.; Docetaxel, Avastin; adjuvant Epirubicin, Cyclophosphamid

Trastuzumab DRUG

Also known as: Herceptin

Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.

Bevacizumab DRUG

Also known as: Avastin

Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.; Docetaxel, Avastin; adjuvant Epirubicin, Cyclophosphamid

Epirubicin DRUG

Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.; Docetaxel, Avastin; adjuvant Epirubicin, Cyclophosphamid

Cyclophosphamid DRUG

Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.; Docetaxel, Avastin; adjuvant Epirubicin, Cyclophosphamid

Eligibility Criteria

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

You may qualify if:

• Arm A / Arm B
• Age ≥ 18 years and ≤ 65 years
• Female
• Operable, locally advanced primary breast cancer (≥ cT2, N0 or N+, M0) histologically confirmed by core biopsy
• Histologically confirmed unilateral, solitaire breast cancer
• Patients who are candidates for neoadjuvant chemotherapy according to AGO guidelines (www.ago-online.de) with unifocal lesion
• HER2 positive disease (IHC 3+ and/or FISH positive)or
• HER2 negative disease (IHC 0/1+, IHC 2+ and/or FISH negative)
• Baseline LVEF ≥ 55% (measured by MUGA or echocardiography) according to institution specific norm
• Informed consent for clinical trial including analysis of predictive imaging tests and biomarkers
• Clinically or by imaging (mammogram, MRI or US) assessed breast cancer ≥ 2 cm or inflammatory breast cancer with bi-dimensional measurable lesion independent of nodal status
• Negative pregnancy test (urine or serum) within 7 days prior to registration if patient is premenopausal with intact reproductive organs and if patient is less than one year after menopause
• ECOG Performance status 0-2
• Adequate organ function for cytotoxic chemotherapy
• Adequate renal function including Serum creatinine ≤ ULN, Measured or calculated creatinine clearance \> 60 ml/min

You may not qualify if:

• Arm A / Arm B
• Evidence of distant metastases by clinical or imaging diagnosis
• Multifocal primary tumour, defined as histologically confirmed tumour-manifestations within different quadrants; distance ≥ 4 cm
• Pre-existing motor or sensory neuropathy of a severity ≥ grade 2 NCI criteria
• Previous breast cancer
• Prior malignancy with a disease-free survival of \< 5 years
• Prior malignancy which has not been curatively treated
• Inflammatory breast cancer without bi-dimensional measurable lesion
• Prior systemic therapy for cancer
• Previous therapy with trastuzumab or other anti-HER2 agent (for HER2+ tumors)
• Previous therapy with bevacizumab or other anti-VEGF agent
• Patients with immunosuppressive therapy
• Pregnant or lactating women
• Women of childbearing potential not using highly effective birth control.
• Patients with known hypersensitivity reactions to the compounds or incorporated substances of trastuzumab or its constituents (for HER2+ tumors).

Sponsors & Collaborators

• West German Study Group: lead
• Roche Pharma AG: collaborator
• Sanofi: collaborator

Study Sites (1)

Breast Centre, University of Munich, LMU

Munich, Bavaria, 81377, Germany

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Docetaxel; Trastuzumab; Bevacizumab; Epirubicin; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Nadia Harbeck, Prof. Dr. med.

  Head of Breast Centre, University of Munich, Grosshadern Hospital, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2012
• First Posted: September 21, 2012
• Study Start: September 1, 2012
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: August 13, 2018

Record last verified: 2018-08

Locations

DE (1)