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

Inflammatory Breast Cancer Clinical Trial

— Beva  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01880385
• Other study ID #: ML25168
• Status: Recruiting
• Phase: Phase 1
• First received: May 25, 2011
• Last updated: June 14, 2013
• Start date: March 2011
• Est. completion date: April 2017

Study information

• Verified date: June 2013
• Source: Association Tunisienne de lutte Contre le Cancer
• Contact: ghozlane lakhoua
• Phone: 0021698354190
• Email: ghozlane_lakhoua[@]hotmail.fr
• Is FDA regulated: No
• Health authority: Tunisia : Direction de la pharmacie et du médicament
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: April 2017
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 75 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Inflammatory Breast Cancer

Intervention

Biological:
• Bevacizumab
During neoadjuvant phase: 15 mg/kg, d1 q3w, 4 cycles

Drug:
• Cyclophosphamide
Neoadjuvant: 500 mg/m2 d1 q3w, 4 cycles
• epirubicin hydrochloride
Neoadjuvant: 100 mg/m2, d1 q3w, 4 cycles
• fluorouracil
Neoadjuvant: 500 mg/m2, d1 q3w, 4 cycles
• 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

Locations

Country	Name	City	State
Tunisia	Institut Salah Azaiz	Bab Saadoun	Tunis

Sponsors (3)

Lead Sponsor	Collaborator
Association Tunisienne de lutte Contre le Cancer	Hoffmann-La Roche, Sanofi

Country where clinical trial is conducted

Tunisia, 

References & Publications (1)

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. Epub 2006 Jan 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	pathologic Complete Response (pCR)	Evaluation of the pathologic complete response (pCR) rate among patients treated by 4 cycles of FEC100 and bevacizumab	18 months	No
Secondary	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	Yes
Secondary	Progression-free survival		3 and 5 years	No
Secondary	Overall survival		3 and 5 years	No