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

NCT ID: NCT01484080

Last Updated: 2020-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2014-04-30

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).

Detailed Description

This is an open-label, multicenter, Phase I dose-escalation study to assess the safety and tolerability of oral (PO) BIBF 1120 administered with intravenous (IV) paclitaxel (80 mg/m2 on days 1, 8 and 15 every 3 weeks) to patients with breast cancer (see Figure 1 for the study flow chart). BIBF 1120 will be administered twice daily PO for 21 consecutive days (Days 1 to 21) in 3-week cycles (morning dose is skipped on the paclitaxel administration days)

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I: BIBF1120+Paclitaxel

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

Group Type: EXPERIMENTAL

BIBF + Paclitaxel

Intervention Type: 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 II: Paclitaxel

Paclitaxel monotherapy treatment will start within 2 weeks after randomization.

Group Type: ACTIVE_COMPARATOR

Paclitaxel

Intervention Type: 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.

Interventions

BIBF + Paclitaxel

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).

Intervention Type: DRUG

Paclitaxel

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Signed Informed Consent Form

2. Patients ≥18 year-old

3. 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.

4. HER 2 negative (Inmunohistochemistry - or + over +++; FISH CISH (-); equivalent to HER2/CEP17 copies under 2: HER2 result ++/+++ needs FISH/CISH confirmation.

5. Measurable disease with a primary lesion >2 cm. by RECIST v1.1 criteria

6. ECOG 0-1

7. 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

8. 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.

9. For female with childbearing potential, a negative pregnancy test within the prior 7 days to the study enrolment

10. Life expectancy >6 months

Exclusion Criteria

1. Metastatic or non-surgical breast cancer (including inflammatory).

2. 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.

3. Previous or concurrent treatment of any kind for breast cancer: hormonal agents, conventional cytotoxic drugs, radiation therapy, targeted drugs, bisphosphonates, monoclonal antibodies or surgery. Chemoprevention with tamoxifen or raloxifene is allowed as far as the treatment was interrupted upon diagnosis and at least 4 weeks prior to inclusion. Same criteria for post-menopausal hormonal replacement therapy. Hormonal contraceptives should be discontinued.

4. HER-2 positive breast cancer defined as over-expression in Immunochemistry of HER-2 3+ or 2+ with positive FISH/CISH

5. Male patients.

6. Pregnancy, lactation or breastfeeding.

7. 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.

8. 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.

9. Inability to take oral medication

10. History of malabsorption syndrome

11. Proven allergy to paclitaxel or BIBF 1120.

12. Grade ≥2 peripheral neuropathy.

14. Inability to comply with the study and follow-up procedures.

15. 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.

16. History of hemorrhagic or thromboembolic event clinically significant in the last 6 months.

17. Known hereditary predisposition to bleeding or thrombosis

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hospital Universitario de Fuenlabrada

OTHER

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: collaborator

Hospital Universitari de Bellvitge

OTHER

Sponsor Role: collaborator

Grupo Espanol de Investigacion del Cancer de Mama

OTHER

Sponsor Role: collaborator

Centro Nacional de Investigaciones Oncologicas CARLOS III

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Miguel Ángel Quintela, M.D.,PhD

Role: STUDY_DIRECTOR

CNIO

Ramón Colomer, M.D.,PhD

Role: PRINCIPAL_INVESTIGATOR

CNIO

Locations

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitario de Fuenlabrada

Fuenlabrada, Madrid, Spain

MD Anderson Cancer Centre Madrid

Madrid, , Spain

Countries

Spain

Other Identifiers

CNIO-BR-01-2010/GEICAM/2010-10

Identifier Type: -

Identifier Source: org_study_id