Breast CancerPhase 1/2NCT01484080
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
A Phase 1/2 study testing BIBF + Paclitaxel and Paclitaxel in people with Breast Cancer, run by Centro Nacional de Investigaciones Oncologicas CARLOS III at 3 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- BIBF + Paclitaxel and Paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 3 sitesSpain
- Study dates
- Oct 2011to Apr 2014
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Life expectancy >6 months
Who cannot join
- 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.
- 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.
- 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.
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- 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.
- Major surgery within 4 weeks of registration (breast cancer surgery regardless of timing is an exclusion criteria).
- 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
Trial locations and contacts
3 sites in 1 country.
Spain3 sites
Hospital Universitario de Fuenlabrada
Fuenlabrada, Madrid, 28942
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
MD Anderson Cancer Centre Madrid
Madrid, 28033
About this study
Official title: Phase I/II Randomized Clinical Trial of 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
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).
Read the 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
- Being tested
- BIBF + Paclitaxel, Paclitaxel
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BIBF + PaclitaxelDrug
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).
PaclitaxelDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm I: BIBF1120+Paclitaxel | Experimental | 2 weeks run-in of BIBF 1120 alone followed by paclitaxel + BIBF 1120 combination Receives: Drug: BIBF + Paclitaxel |
| Arm II: Paclitaxel | Active comparator | Paclitaxel monotherapy treatment will start within 2 weeks after randomization. Receives: Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Within 30 days after surgery
Secondary outcomes (1)
Determine predicting factors at the phosphoproteomic signature and its correlation with response to BIBF-1120
- Determination of phosphoproteomic signatures in tumor biopsy. Patients in arm-2 will undergo a baseline biopsy with the aim of establishing a signature predicting response to docetaxel alone, and by comparison with the signature in the arm-1, extracting the signalling nodes implicated in docetaxel response from those implicated in angiogenic blockade response.
Measured: Baseline and end of priming phase.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2011 (estimated)
- Study startOct 2011
- Primary completionNov 2013
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centro Nacional de Investigaciones Oncologicas CARLOS III
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Universitario de Fuenlabrada, M.D. Anderson Cancer Center, Hospital Universitari de Bellvitge, Grupo Espanol de Investigacion del Cancer de Mama
- Responsible party
- Sponsor
- Investigators
- Miguel Ángel Quintela, M.D.,PhD, Study director, CNIORamón Colomer, M.D.,PhD, Principal investigator, CNIO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01484080
- Sponsor's protocol ID
- CNIO-BR-01-2010/GEICAM/2010-10
- Status last verified
- Jan 2020
- First submitted
- 21 Oct 2011
- Last updated
- 27 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Randomized Clinical Trial of 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
- ClinicalTrials.gov ID
- NCT01484080
- Acronym / sponsor ID
- CNIO-BR-01-2010/GEICAM/2010-10
- Conditions
- Breast Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- Centro Nacional de Investigaciones Oncologicas CARLOS IIIUniversity, hospital or other
- Collaborators
- Hospital Universitario de Fuenlabrada, M.D. Anderson Cancer Center, Hospital Universitari de Bellvitge, Grupo Espanol de Investigacion del Cancer de Mama
- Study start
- Oct 2011
- Primary completion
- Nov 2013 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 2 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I: BIBF1120+Paclitaxel | Experimental | Drug: BIBF + Paclitaxel2 weeks run-in of BIBF 1120 alone followed by paclitaxel + BIBF 1120 combination |
| Arm II: Paclitaxel | Active comparator | Drug: PaclitaxelPaclitaxel monotherapy treatment will start within 2 weeks after randomization. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (17 listed)
- 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.
- 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.
- HER-2 positive breast cancer defined as over-expression in Immunochemistry of HER-2 3+ or 2+ with positive FISH/CISH
- Male patients.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BIBF + PaclitaxelPriming 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). | Drug | Arm I: BIBF1120+Paclitaxel |
| PaclitaxelPaclitaxel 80 mg/m2 iv on days 1, 8 and 15 q 21 days. A total of 4 cycles will be administered in both arms. | Drug | Arm II: Paclitaxel |
Primary outcome
Pathologic complete response
Time frame: Within 30 days after surgery
Pathologic complete response defined as the absence of tumor cells assessed on the surgical specimen + residual Ductal Carcinoma In Situ (DCIS) in the breast.
1 secondary outcome
Determine predicting factors at the phosphoproteomic signature and its correlation with response to BIBF-1120
Time frame: Baseline and end of priming phase.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Miguel Ángel Quintela, M.D.,PhD study director
CNIO
Ramón Colomer, M.D.,PhD principal investigator
CNIO
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BIBF + Paclitaxel and Paclitaxel in people with Breast Cancer, run by Centro Nacional de Investigaciones Oncologicas CARLOS III at 3 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic complete response (time frame: Within 30 days after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2020.