Efficacy and Safety of Bevacizumab in the Neodjuvant Treatment of Inflammatory Breast Cancer
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
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 Design
Arms and Interventions
Arm | Intervention/Treatment |
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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:
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
|
Outcome Measures
Primary Outcome Measures
- pathologic Complete Response (pCR) [18 months]
Evaluation of the pathologic complete response (pCR) rate among patients treated by 4 cycles of FEC100 and bevacizumab
Secondary Outcome Measures
- Toxicity as assessed by CTCAE v3.0 [3 and 5 years]
Evaluation of the safety of administering bevacizumab in the neoadjuvant setting, with particular attention on the incidence of grade 3/4 adverse events
- Progression-free survival [3 and 5 years]
- Overall survival [3 and 5 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
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• Patients must have signed a written informed consent form prior to any study specific procedures,
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Women,
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20 years or older,
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Performance status < 2 (ECOG),
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Histologically confirmed inflammatory breast cancer T4d any N,
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hormonal Status known,
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no metastases according to the last TNM classification,
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adequate hematologic function :
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absolute neutrophil count ≥ 1 500/mm3
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Platelets ≥ 100 000/mm3
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Hemoglobin ≥ 9 g/dL
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adequate liver function :
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ASAT and ALAT < à 3 ULN
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Alkaline Phosphatase < 5 ULN
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Total bilirubin < 1,5 ULN, o
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adequate kidney function :
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creatinine < 1,5 x normal or creatinine Clearance ≥ 50ml/min (according to the cockcroft and Gault formula)
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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,
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adequate coagulation and cardiac function :
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Prothrombin ratio ≥ 70 % and,
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Prothrombin time ≤ 1,5 upper limit of normal (ULN) within 7 days prior to enrolment
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Left Ventricular ejection fraction (LVEF) ≥ 55 %
Exclusion Criteria:
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Patients of childbearing potential with a positive pregnancy test (serum or urine) prior to enrollment
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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)
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Patients who are pregnant or breastfeeding
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Patient considered socially or psychological unable to comply with the treatment and the required medial follow-up,
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Concurrent participation in another clinical trial or treatment with any other anticancer agent during the protocol specified period
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Patients unwilling or unable to sign and date an Ethics Committee (EC)/ Institutional Review Board (IRB)-approved patient informed consent form
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Patients unwilling or unable to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
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Non inflammatory breast cancer with lymphatic skin permeation, Metastases,
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Bilateral breast cancer
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Distant metastases (stage IV)
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History of another cancer other than adequately treated carcinoma in situ of the cervix uteri, basal or squamous cell skin cancer
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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
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History or evidence of inherited bleeding diathesis or coagulopathy,
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History of thrombotic disorders within the last 6 months prior to enrollment (i.e. cerebrovascular accident, transient ischemic attacks, subarachnoid hemorrhage),
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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,
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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)
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Severe resting dyspnea due to complications or oxygen dependency,
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Diabetic patient treated with oral anti-diabetics or insulin with an underlying cardiopathy at ultrasound,
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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
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Other severe underlying medical conditions, which could impair the ability to participate in the study
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Major surgery, significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during study treatment,
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Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion,
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Non-healing wound, active peptic ulcer or bone fracture,
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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,
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Institut Salah Azaiz | Bab Saadoun | Tunis | Tunisia | 1006+ |
Sponsors and Collaborators
- Association Tunisienne de lutte Contre le Cancer
- Hoffmann-La Roche
- Sanofi
Investigators
- Principal Investigator: amel mezlini, professor, Institut Salah Azaiz
Study Documents (Full-Text)
None provided.More Information
Publications
- ML25168