Addition of Vismodegib to Neoadjuvant Chemotherapy in Triple Negative Breast Cancer Patients

NCT ID: NCT02694224

Last Updated: 2017-10-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-04-30

Study Completion Date

2018-12-31

Brief Summary

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To evaluate safety and efficacy of vismodegib with standard neoadjuvant chemotherapy in breast cancer patients based on the CTCAE v4 2010

1. To study changes in biomarkers involved in the Hedgehog (HH) pathway in the first biopsy as compared to the later one
2. To detect predictive factors among patients who reached pathological complete response (pCR) as compared to those with no pCR
3. To evaluate the role of the addition of vismodegib in the pCR rate
4. To evaluate clinical responses by breast MRI and rates of breast conservative surgery after neoadjuvant chemotherapy
5. To evaluate QOL with EORTC QLQ-C30 scale

Detailed Description

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Conditions

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Breast Cancer

Keywords

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breast cancer triple negative neoadjuvant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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vismodegib plus chemotherapy

Vismodegib 150 mg orally during paclitaxel and then dose dense epirubicin + cyclophosphamide (EC) therapy (see active comparator arm)

Group Type EXPERIMENTAL

vismodegib

Intervention Type DRUG

Smo inhibitor

Paclitaxel

Intervention Type DRUG

Paclitaxel (80 mg/m2) weekly x 12 doses followed by sequential dose dense Epirubicin (90 mg/m2) plus Cyclophosphamide (600 mg/m2) each 2 weeks x 4 doses with granulocyte macrophage colony stimulating factors (GM-CSF) support

Epirubicin

Intervention Type DRUG

dose dense Epirubicin (90 mg/m2) plus Cyclophosphamide each 2 weeks x 4 doses with GMCSF after Paclitaxel

Cyclophosphamide

Intervention Type DRUG

dose dense Cyclophosphamide (600 mg/m2) together with Epirubicin each 2 weeks x 4 doses with GMCSF after Paclitaxel

chemotherapy

Paclitaxel 80 mg/m2 weekly on days 1, 8 and 15 each 21 days x 12 doses and then dose dense E (90 mg/m2) plus cyclophosphamide (CPA) 600 mg/m2 each 2 weeks x 4 doses

Group Type ACTIVE_COMPARATOR

Paclitaxel

Intervention Type DRUG

Paclitaxel (80 mg/m2) weekly x 12 doses followed by sequential dose dense Epirubicin (90 mg/m2) plus Cyclophosphamide (600 mg/m2) each 2 weeks x 4 doses with granulocyte macrophage colony stimulating factors (GM-CSF) support

Epirubicin

Intervention Type DRUG

dose dense Epirubicin (90 mg/m2) plus Cyclophosphamide each 2 weeks x 4 doses with GMCSF after Paclitaxel

Cyclophosphamide

Intervention Type DRUG

dose dense Cyclophosphamide (600 mg/m2) together with Epirubicin each 2 weeks x 4 doses with GMCSF after Paclitaxel

Interventions

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vismodegib

Smo inhibitor

Intervention Type DRUG

Paclitaxel

Paclitaxel (80 mg/m2) weekly x 12 doses followed by sequential dose dense Epirubicin (90 mg/m2) plus Cyclophosphamide (600 mg/m2) each 2 weeks x 4 doses with granulocyte macrophage colony stimulating factors (GM-CSF) support

Intervention Type DRUG

Epirubicin

dose dense Epirubicin (90 mg/m2) plus Cyclophosphamide each 2 weeks x 4 doses with GMCSF after Paclitaxel

Intervention Type DRUG

Cyclophosphamide

dose dense Cyclophosphamide (600 mg/m2) together with Epirubicin each 2 weeks x 4 doses with GMCSF after Paclitaxel

Intervention Type DRUG

Other Intervention Names

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GDC0449

Eligibility Criteria

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Inclusion Criteria

1. Female sex
2. Ability to give informed agreement and to carry out the whole study protocol during the study period
3. The patient should be able to carry out the needs of the clinical trial and have measurable disease
4. The patient should be 18-75 year-old
5. Triple negative breast cancer (ER\<1%, Progesteron Receptor (PR)\<1%, non-overexpressing HER2). 1. Patients with oligometastatic disease (1-2 resectable metastases) could be included
6. No previous systemic therapies
7. Patients who are going to benefit from neoadjuvant chemotherapy
8. Eastern Cooperative Oncology Group (ECOG)\<2 or Karnofsky≥70%
9. Blood tests and biochemistry suitable: (absolute neutrophil count\> 1500/uL; haemoglobin\>9 gr/dL; platelets\>100000/uL (microliters); total bilirubin≤ 1.5 the upper normal limit; GOT and GPT (transaminases)≤twice the upper normal limit; fasting glucose≤150 gr/dL; HbA1c≤8%, serum creatinine≤2 mg/dL.

Exclusion Criteria

1. Severe diseases or infectious diseases or liver, kidney or bone marrow failure that advise not to participate in the study according to investigator criteria
2. Pregnancy or breast feeding period or fertility women who are not agree with contraception methods
3. Other primary tumors except for breast in situ carcinoma (CIS), cervical neoplasia(CIN) or localized skin tumors
4. Inflammatory breast cancer or bilateral breast cancer
5. Bone fractures, peptic ulcus or healing disorders
6. Any local or systemic therapy for breast cancer
7. To be maintained on immunosuppressants (prednisone \> 10 mgr daily or others), aspirin\> 325 mgr per day or clopidogrel \> 75 mgr daily
8. Cardiomyopathy by New York Heart Association (NYHA) class II-IV; heart stroke in the previous 6 months; uncontrolled blood pressure (systolic \> 150 mm Hg and /or diastolic \> 100 mm Hg), coagulopathy or hemorrhagic diseases
9. Previous lung diseases
10. Personal history of abdominal perforation, abdominal abscess, or abdominal fistula.
11. Inability to swallow pills
12. Intolerance to galactose, malabsorption to galactose or/and glucose, or primary hypolactasia
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Clinica Universidad de Navarra, Universidad de Navarra

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Santisteban Marta, Doctor

Role: PRINCIPAL_INVESTIGATOR

Staff of the department of Oncology

Locations

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Clínica Universidad de Navarra

Pamplona, Navarre, Spain

Site Status RECRUITING

Countries

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Spain

Central Contacts

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Amaya Izal

Role: CONTACT

Phone: +34948255400

Email: [email protected]

Joana Reis, Nurse

Role: CONTACT

Phone: +34948255400

Email: [email protected]

Facility Contacts

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Amaya Izal

Role: primary

Other Identifiers

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SHH (Sonic HedgeHog)-CM

Identifier Type: -

Identifier Source: org_study_id