Neoadjuvant Paclitaxel Versus BIBF 1120 Priming Followed by BIBF 1120 Plus Paclitaxel in Early HER-2 Negative Breast Cancer With Proteomic and Dynamic Imaging Correlates

NCT01484080 | Completed Phase 1 DMC

• 1 other identifier: CNIO-BR-01-2010/GEICAM/2010-10
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 3

Brief Summary

The investigators plan to study the efficacy of the combination of weekly paclitaxel + BIBF 1120 in early breast cancer using a neoadjuvant schedule and a randomized phase-II trial design, comparing the efficacy vs. weekly paclitaxel alone, followed by surgery and subsequent standards of care (anthracycline based chemotherapy, radiation or hormonal blockade).

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response

  Pathologic complete response defined as the absence of tumor cells assessed on the surgical specimen + residual Ductal Carcinoma In Situ (DCIS) in the breast.

  Within 30 days after surgery

Secondary Outcomes (1)

• Determine predicting factors at the phosphoproteomic signature and its correlation with response to BIBF-1120

  Baseline and end of priming phase.

Study Arms (2)

Arm I: BIBF1120+Paclitaxel

EXPERIMENTAL

2 weeks run-in of BIBF 1120 alone followed by paclitaxel + BIBF 1120 combination

Drug: BIBF + Paclitaxel

Arm II: Paclitaxel

ACTIVE COMPARATOR

Paclitaxel monotherapy treatment will start within 2 weeks after randomization.

Drug: Paclitaxel

Interventions

BIBF + Paclitaxel DRUG

Priming Period: Oral BIBF 1120 will be administered during 2 weeks at the dose determined during the phase-I part that can be combined safely with weekly paclitaxel, on a continuous schedule for 14 days. One week washout is planned before starting the treatment phase. Treatment Phase: Paclitaxel 80 mg/m2 iv on days 1, 8 and 15 + BIBF 1120 recommended dose bid po days 1-21 q 21 days. (BIBF 1120 morning dose is skipped on the paclitaxel administration days).

Arm I: BIBF1120+Paclitaxel

Paclitaxel DRUG

Paclitaxel 80 mg/m2 iv on days 1, 8 and 15 q 21 days. A total of 4 cycles will be administered in both arms.

Arm II: Paclitaxel

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Form
• Patients ≥18 year-old
• Histological diagnosis of localized breast cancer with primary tumour over 2 cm on its longest diameter (measured by mammography and MRI). Any nodal status is allowed when it is an operable tumour at diagnosis. Multicentricity is allowed.
• HER 2 negative (Inmunohistochemistry - or + over +++; FISH CISH (-); equivalent to HER2/CEP17 copies under 2: HER2 result ++/+++ needs FISH/CISH confirmation.
• Measurable disease with a primary lesion \>2 cm. by RECIST v1.1 criteria
• ECOG 0-1
• Adequate hematologic, renal and hepatic function, defined by the following laboratory results obtained within 14 days prior to randomization/registration:
• Absolute granulocyte count \>1.5 x 109/L
• Absolute platelet count \>100 x 109/L
• Hemogobin \>10 g/dL
• Serum creatinine \>1.5 x UNL or a calculated creatinine clearance \>50 ml/min
• Serum bilirubin \<1.25 UNL
• AST/ALT \<1.5 times UL
• Premenopausal women must be under effective birth control (non-hormone) and continue its use for the duration of the study and even 6 months later.
• For female with childbearing potential, a negative pregnancy test within the prior 7 days to the study enrolment

You may not qualify if:

• Metastatic or non-surgical breast cancer (including inflammatory).
• Locally breast cancer with primary lesion under 2 cm. In case of multicentricity, it will not be admitted in the study unless any lesion would be over this length.
• HER-2 positive breast cancer defined as over-expression in Immunochemistry of HER-2 3+ or 2+ with positive FISH/CISH
• Male patients.
• Pregnancy, lactation or breastfeeding.
• Active malignancy at any other side (including contra-lateral synchronous breast cancer) besides non-melanoma skin cancer or ductal/lobular of the breast or cervix in situ carcinoma, colon in situ carcinoma accurately treated as well as any other tumour diagnosis \>5 years prior to registration without any sign of progression at present time.
• Concurrent serious medical conditions such as myocardial infarction within 6 months prior to entry, congestive heart failure, unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, uncontrolled hypertension (under NYHA criteria), uncontrolled psychotic disorders, serious active infections, active peptic ulcer disease, psychiatric illness, HIV infection, active hepatitis, COPD or any other medical conditions that might be aggravated by treatment or limit compliance.
• Inability to take oral medication
• History of malabsorption syndrome
• Proven allergy to paclitaxel or BIBF 1120.
• Grade ≥2 peripheral neuropathy.
• Inability to comply with the study and follow-up procedures.
• Anticoagulation therapy (except low-dose heparin and / or wash out with heparin as needed to maintain a permanent intravenous device) or antiplatelet therapy (except for treatment with low doses of aspirin \<325 mg per day.
• History of hemorrhagic or thromboembolic event clinically significant in the last 6 months.
• Known hereditary predisposition to bleeding or thrombosis

Sponsors & Collaborators

• Centro Nacional de Investigaciones Oncologicas CARLOS III: lead
• Hospital Universitario de Fuenlabrada: collaborator
• M.D. Anderson Cancer Center: collaborator
• Hospital Universitari de Bellvitge: collaborator
• Grupo Espanol de Investigacion del Cancer de Mama: collaborator

Study Sites (3)

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitario de Fuenlabrada

Fuenlabrada, Madrid, 28942, Spain

Location

MD Anderson Cancer Centre Madrid

Madrid, 28033, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel

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

Study Officials

• Miguel Ángel Quintela, M.D.,PhD

  CNIO

  STUDY DIRECTOR

• Ramón Colomer, M.D.,PhD

  CNIO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2011
• First Posted: December 2, 2011
• Study Start: October 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: April 1, 2014
• Last Updated: January 27, 2020

Record last verified: 2020-01

Locations

ES (3)