Bevacizumab in Combination With Chemotherapy in the Neo-adjuvant Setting for HER2 (-) Breast Cancer

NCT01985841 | Terminated Phase 2

• 1 other identifier: CT/10.15
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 6

Brief Summary

Investigators propose to study the efficacy of Bevacizumab plus systemic chemotherapy prior to surgery in order to make a locally advanced tumor operable. Treatment is thus expected to induce a maximum tumor shrinkage within a short period (usually 3-6 months). In addition Bevacizumab (Avastin) is to be administered as early as possible during the disease stages. The primary aim of this study is to evaluate the preliminary antitumor activity in terms of pathological complete responses (pCR) of bevacizumab in combination with chemotherapy.

Conditions

Breast Cancer

Keywords

Early breast cancer; Primary operable breast cancer; HER2- negative; bevacizumab

Outcome Measures

Primary Outcomes (1)

• Number of Patients with Complete Response

  Patients will be assessed for tumor response on week 8 and on week 16. Patients with tumor reduction will proceed on surgery. Histology report will confirm the complete or partial responses to chemotherapy.

  On week 8 and 16

Secondary Outcomes (2)

• Overall Survival

  3 years

• Progression Free Survival

  5 years

Study Arms (1)

Bevacizumab/FEC/Docetaxel

EXPERIMENTAL

Bevacizumab plus 5-Fluorouracil/Epirubicin/Cyclophosphamide (FEC) -\> Bevacizumab plus Docetaxel

Drug: Bevacizumb; Drug: 5-Fluorouracil; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Docetaxel

Interventions

Bevacizumb DRUG

Avastin

Also known as: Bevacizumab: 10 mg/kg for up to 8 cycles from date of first dose, (cycle repeated every two weeks)

Bevacizumab/FEC/Docetaxel

5-Fluorouracil DRUG

5-FU

Also known as: 5-Fluorouracil: 700mg/m2 for up to 4 cycles from date of first dose, (cycle repeated every two weeks)

Bevacizumab/FEC/Docetaxel

Epirubicin DRUG

Farmorubicin

Also known as: Epirubicin: 75mg/m2 for up to 4 cycles from date of first dose, (cycle repeated every two weeks)

Bevacizumab/FEC/Docetaxel

Cyclophosphamide DRUG

Endoxan

Also known as: Cyclophosphamide: 700mg/m2 for up to 4 cycles from date of first dose, (cycle repeated every two weeks)

Bevacizumab/FEC/Docetaxel

Docetaxel DRUG

Taxotere

Also known as: Docetaxel: 75mg/m2 for up to 4 cycles from date of first dose, (cycle repeated every two weeks)

Bevacizumab/FEC/Docetaxel

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients with histologic proven, corebiopsied, invasive ductal adenocarcinoma of the breast \>2 cm in size and of any N stage (clinical and/or radiological T-stage \> T1, including T4d), scheduled to receive preoperative chemotherapy.
• Age 18-70 years
• ECOG performance-status ≤1
• No prior or current neoplasm except for curatively treated non melanoma skin cancer, in situ carcinoma of the cervix
• No distant disease/secondary carcinoma
• Normal cardiac function
• bilateral Mammography (before enrolment)
• histology
• grading
• hormone-receptor-status
• HER2 status negative (is defined as FISH/CISH negative or IHC0 or IHC1+, or IHC2+ and FISH/CISH negative)
• Laboratory requirements (within 1 week before enrolment):
• Hematology: Neutrophils ≥ 1.5 x 109/l, Platelets ≥ 100 x 109/l, Hemoglobin\>11 g/dl
• Hepatic function: Total bilirubin \< 1 x ULN, SGOT and SGPT \< 1.5 x ULN, Alkaline phosphatases \< 1.5 x ULN. In case of abnormal values, the liver function tests have to be repeated within 3 days before study treatment.
• Renal function: Creatinine \< 1 x ULN

You may not qualify if:

• Cytological only confirmation of diagnosis
• Lobular or other non-ductal types of breast cancer
• Pregnant, or lactating patients; patients of childbearing potential must implement adequate contraceptive measures during study participation
• Pre-existing motor or sensory neurotoxicity of a severity \> grade 2 by NCI-CTC AE
• Preoperative local treatment for breast cancer (i.e. incomplete surgery, radiotherapy)
• Prior or concurrent systemic antitumor therapy
• Evidence of wound healing complications, bone fracture, ulcer or the presence of clinically significant peripheral vascular disease
• Clinically significant cardiac disease e.g. congestive heart failure.
• Other serious illness or medical condition-uncontrolled hypertension or high risk uncontrolled arrythmias -history of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent-active uncontrolled infection-unstable peptic ulcer, unstable diabetes mellitus or other contraindication for the use of corticosteroids
• Known hypersensitivity reaction to the compounds or incorporated substances.
• Evidence of bleeding diathesis or coagulopathy
• The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR, or appropriate monitoring test is within therapeutic limits and the patient has been on a stable dose of anticoagulants for at least two weeks at the time of randomization. Patients not receiving anti coagulant medication must have an INR ≤ 1.5 an aPTT ≤ 1.5 x ULN within 7 days of randomization.
• Ongoing treatment with aspirin (\> 325mg / day) or other medications known to predispose to gastrointestinal ulceration.
• Major surgery (including open biopsy), significant traumatic injury within 28 days prior to enrolment.
• Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion

Sponsors & Collaborators

• Hellenic Oncology Research Group: lead

Study Sites (6)

"IASO" General Hospital of Athens

Athens, Greece

Location

Air Forces Military Hospital of Athens

Athens, Greece

Location

University Hospital of Crete, Dep of Medical Oncology Heraklion, Greece

Heraklion, Greece

Location

"Metaxa's" Anticancer Hospital of Piraeus, 1st Dep of Medical Oncology

Piraeus, Greece

Location

"Euromedica" Hospital of Thessaloniki

Thessaloniki, Greece

Location

"Theagenion" Anticancer Hospital of Thessaloniki, 2nd Dep of Medical Oncology

Thessaloniki, Greece

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Bevacizumab; Fluorouracil; Epirubicin; Cyclophosphamide; Docetaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Study Officials

• Dimitris Mavroudis, MD

  Hellenic Oncology Research Group

  PRINCIPAL INVESTIGATOR

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: September 13, 2013
• First Posted: November 15, 2013
• Study Start: October 1, 2011
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: October 8, 2015

Record last verified: 2015-10

Locations

GR (6)