Efficacy and Safety of Bevacizumab in the Neodjuvant Treatment of Inflammatory Breast Cancer (Beva)

Efficacy & Safety of Bevacizumab as Neoadjuvant Treatment in Patients With Locally Advanced Inflammatory Breast Cancer, a Pilot Study.

Multi-center, non randomised, open label, non controlled pilot study. Evaluating the treatment of bevacizumab in association with pre-operative chemotherapy, followed by surgery, adjuvant chemotherapy and radiotherapy in Patients with inflammatory breast cancer.

Study Overview

• Status: Unknown
• Conditions: Inflammatory Breast Cancer
• Intervention / Treatment: Biological: Bevacizumab; Drug: Cyclophosphamide; Drug: epirubicin hydrochloride; Drug: fluorouracil; Drug: Docetaxel; Biological: Trastuzumab

Detailed Description

Pilot study evaluating the safety and efficacy of adding Bevacizumab to neoadjuvant chemotherapy in patients presenting non metastatic inflammatory breast cancer (IBC). Patients will receive 4 cycles of chemotherapy FEC100 associating Fluorouracil (500 mg/m2), Epirubicin (100 mg/m2), Cyclophosphamide (500 mg/m2) and Bevacizumab 15 mg/kg every at day 1 of ecah 21 days cycle for 4 cycles. Six weeks after the end of neoadjuvant chemotherapy, patients will undergo mastectomy and 4 cycles of Docetaxel (100 mg/m2)as adjuvant chemotherapy +/-Trastuzumab 8 mg/kg for the first cycle then 6mg/kg every 3 weeks for 17 cycles if tumor overexpress Human Epidermal Growth Factor Receptor 2 (HER2).

The primary objective of this study is to evaluate the safety and the efficacy, i.e. pathologic complete response (pCR) after 4 cycles of FEC100+Bevacizumab in IBC

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: ghozlane lakhoua; Phone Number: 0021698354190; Email: ghozlane_lakhoua@hotmail.fr

Study Locations

• Tunisia
  • Tunis
    • Bab Saadoun, Tunis, Tunisia, 1006+
      • Recruiting
      • Institut Salah Azaiz
      • Contact: ghozlane lakhoua; Phone Number: 00 216 98 354 190; Email: ghozlane_lakhoua@hotmail.fr
      • Sub-Investigator: henda raies, professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• • Patients must have signed a written informed consent form prior to any study specific procedures,

  • Women,
  • 20 years or older,
  • Performance status < 2 (ECOG),
  • Histologically confirmed inflammatory breast cancer T4d any N,
  • hormonal Status known,
  • no metastases according to the last TNM classification,

  • adequate hematologic function :

    • absolute neutrophil count ≥ 1 500/mm3
    • Platelets ≥ 100 000/mm3
    • Hemoglobin ≥ 9 g/dL

  • adequate liver function :

    • ASAT and ALAT < à 3 ULN
    • Alkaline Phosphatase < 5 ULN
    • Total bilirubin < 1,5 ULN, o

  • adequate kidney function :

    • creatinine < 1,5 x normal or creatinine Clearance ≥ 50ml/min (according to the cockcroft and Gault formula)
    • Urine Dipstick for proteinuria < 2+ patients who have proteinuria ≥ 2 + on dipstick urinalysis at baseline should undergo a 24 hours urine collection and must demonstrate ≤ 1 g of protein in 24 hours,

  • adequate coagulation and cardiac function :

    • Prothrombin ratio ≥ 70 % and,
    • Prothrombin time ≤ 1,5 upper limit of normal (ULN) within 7 days prior to enrolment
    • Left Ventricular ejection fraction (LVEF) ≥ 55 %

Exclusion Criteria:

• Patients of childbearing potential with a positive pregnancy test (serum or urine) prior to enrollment
• Patients who are either not post-menopausal, or surgically sterile, not using "effective contraception" (the definition of "effective contraception" will be based on the judgment of the investigator)
• Patients who are pregnant or breastfeeding
• Patient considered socially or psychological unable to comply with the treatment and the required medial follow-up,
• Concurrent participation in another clinical trial or treatment with any other anticancer agent during the protocol specified period
• Patients unwilling or unable to sign and date an Ethics Committee (EC)/ Institutional Review Board (IRB)-approved patient informed consent form
• Patients unwilling or unable to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
• Non inflammatory breast cancer with lymphatic skin permeation, Metastases,
• Bilateral breast cancer
• Distant metastases (stage IV)
• History of another cancer other than adequately treated carcinoma in situ of the cervix uteri, basal or squamous cell skin cancer
• Prior anti tumor therapy (surgery, radiotherapy, chemotherapy, hormonal treatment and targeted therapy) except treatments given for carcinoma in situ of the cervix uteri, basal or squamous cell skin cancer
• History or evidence of inherited bleeding diathesis or coagulopathy,
• History of thrombotic disorders within the last 6 months prior to enrollment (i.e. cerebrovascular accident, transient ischemic attacks, subarachnoid hemorrhage),
• Uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg)with or without any anti-hypertensive medication ; patients with high initial blood pressure are eligible if entry criteria are met after initiation or adjustment of anti-hypertensive medication,
• Any of the following within 6 months prior to enrollment:

myocardial infarction, severe/unstable angina, or coronary/peripheral artery bypass graft surgery, clinically symptomatic and uncontrolled cardiovascular disease, or clinically significant cardiac arrhythmias (grade 3-4)

• Severe resting dyspnea due to complications or oxygen dependency,
• Diabetic patient treated with oral anti-diabetics or insulin with an underlying cardiopathy at ultrasound,
• Any other severe acute illness such as active uncontrolled infections that would preclude the safe administration of study therapy at the time of the enrolment
• Other severe underlying medical conditions, which could impair the ability to participate in the study
• Major surgery, significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during study treatment,
• Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion,
• Non-healing wound, active peptic ulcer or bone fracture,
• History of abdominal fistula, diagnosed with a trachea-oesophageal fistula or any grade 4 non gastro-intestinal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: bevacizumab, inflammatory breast cancer; Neoadjuvant therapy associating bevacizumab, cyclophosphamide, fluorouracil and epirubicin hydrochloride q3w, 4 cycles Adjuvant therapy by docetaxel q3w, 4 cycles +/- trastuzumab q3w, 18 cycles if tumors overexpress HER2

Biological: Bevacizumab; During neoadjuvant phase: 15 mg/kg, d1 q3w, 4 cycles; Other Names: Avastin; Drug: Cyclophosphamide; Neoadjuvant: 500 mg/m2 d1 q3w, 4 cycles; Drug: epirubicin hydrochloride; Neoadjuvant: 100 mg/m2, d1 q3w, 4 cycles; Drug: fluorouracil; Neoadjuvant: 500 mg/m2, d1 q3w, 4 cycles; Drug: Docetaxel; Adjuvant: 100 mg/m2 q3w, 4 cycles; Biological: Trastuzumab; Adjuvant: 8 mg/kg d1 in the 1st cycle then 6 mg/kg for d1 q3w, 17 cycles if tumor overexpress HER2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathologic Complete Response (pCR)	Evaluation of the pathologic complete response (pCR) rate among patients treated by 4 cycles of FEC100 and bevacizumab	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity as assessed by CTCAE v3.0	Evaluation of the safety of administering bevacizumab in the neoadjuvant setting, with particular attention on the incidence of grade 3/4 adverse events	3 and 5 years
Progression-free survival		3 and 5 years
Overall survival		3 and 5 years

Collaborators and Investigators

• Sponsor: Association Tunisienne de lutte Contre le Cancer
• Collaborators: Sanofi; Hoffmann-La Roche
• Investigators: Principal Investigator: amel mezlini, professor, Institut Salah Azaiz

Publications and helpful links

General Publications

• Wedam SB, Low JA, Yang SX, Chow CK, Choyke P, Danforth D, Hewitt SM, Berman A, Steinberg SM, Liewehr DJ, Plehn J, Doshi A, Thomasson D, McCarthy N, Koeppen H, Sherman M, Zujewski J, Camphausen K, Chen H, Swain SM. Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. J Clin Oncol. 2006 Feb 10;24(5):769-77. doi: 10.1200/JCO.2005.03.4645. Epub 2006 Jan 3.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Anticipated): September 1, 2013
• Study Completion (Anticipated): April 1, 2017

Study Registration Dates

• First Submitted: May 25, 2011
• First Submitted That Met QC Criteria: June 14, 2013
• First Posted (Estimate): June 19, 2013

Study Record Updates

• Last Update Posted (Estimate): June 19, 2013
• Last Update Submitted That Met QC Criteria: June 14, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: bevacizumab; Avastin; inflammatory breast cancer; non metastatic
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Inflammatory Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antibiotics, Antineoplastic; Docetaxel; Cyclophosphamide; Trastuzumab; Fluorouracil; Epirubicin; Bevacizumab
• Other Study ID Numbers: ML25168