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Addition of Vismodegib to Neoadjuvant Chemotherapy in Triple Negative Breast Cancer Patients (SHH-CM)

Primary Purpose

Breast Cancer

Status

Unknown status

Phase

Phase 2

Locations

Spain

Study Type

Interventional

Intervention

vismodegib

Paclitaxel

Epirubicin

Cyclophosphamide

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring breast cancer, triple negative, neoadjuvant

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Female sex
Ability to give informed agreement and to carry out the whole study protocol during the study period
The patient should be able to carry out the needs of the clinical trial and have measurable disease
The patient should be 18-75 year-old
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
No previous systemic therapies
Patients who are going to benefit from neoadjuvant chemotherapy
Eastern Cooperative Oncology Group (ECOG)<2 or Karnofsky≥70%
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:

Severe diseases or infectious diseases or liver, kidney or bone marrow failure that advise not to participate in the study according to investigator criteria
Pregnancy or breast feeding period or fertility women who are not agree with contraception methods
Other primary tumors except for breast in situ carcinoma (CIS), cervical neoplasia(CIN) or localized skin tumors
Inflammatory breast cancer or bilateral breast cancer
Bone fractures, peptic ulcus or healing disorders
Any local or systemic therapy for breast cancer
To be maintained on immunosuppressants (prednisone > 10 mgr daily or others), aspirin> 325 mgr per day or clopidogrel > 75 mgr daily
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
Previous lung diseases
Personal history of abdominal perforation, abdominal abscess, or abdominal fistula.
Inability to swallow pills
Intolerance to galactose, malabsorption to galactose or/and glucose, or primary hypolactasia

Sites / Locations

Clínica Universidad de NavarraRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

vismodegib plus chemotherapy

chemotherapy

Arm Description

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

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

Outcomes

Primary Outcome Measures

Number of patients with treatment-related adverse events as assessed by CTCAE v4.0

Secondary Outcome Measures

Molecular changes in breast

Pathologic complete response (pCR)

Clinical complete response (cCR)

European Organisation for Research and Treatment of Cancer Quality of Life questionnaire C30 (EORTC QOL-C30)

We will consider data related to quality of life such as weakness, appetite, physical health, physiological health, social relationships, environment etc

Full Information

NCT ID

NCT02694224

First Posted

January 12, 2016

Last Updated

October 23, 2017

Sponsor

Clinica Universidad de Navarra, Universidad de Navarra

1. Study Identification

Unique Protocol Identification Number

NCT02694224

Brief Title

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

Acronym

SHH-CM

Official Title

A Randomized Phase II Pilot Study to Evaluate Safety and Efficacy of the Addition of Vismodegib to Standard Neoadjuvant Chemotherapy in Triple Negative Breast Cancer Patients

Study Type

Interventional

2. Study Status

Record Verification Date

October 2017

Overall Recruitment Status

Unknown status

Study Start Date

April 2016 (undefined)

Primary Completion Date

December 2017 (Anticipated)

Study Completion Date

December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Clinica Universidad de Navarra, Universidad de Navarra

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

To evaluate safety and efficacy of vismodegib with standard neoadjuvant chemotherapy in breast cancer patients based on the CTCAE v4 2010 To study changes in biomarkers involved in the Hedgehog (HH) pathway in the first biopsy as compared to the later one To detect predictive factors among patients who reached pathological complete response (pCR) as compared to those with no pCR To evaluate the role of the addition of vismodegib in the pCR rate To evaluate clinical responses by breast MRI and rates of breast conservative surgery after neoadjuvant chemotherapy To evaluate QOL with EORTC QLQ-C30 scale

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

breast cancer, triple negative, neoadjuvant

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

vismodegib plus chemotherapy

Arm Type

Experimental

Arm Description

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

Arm Title

chemotherapy

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

vismodegib

Other Intervention Name(s)

GDC0449

Intervention Description

Smo inhibitor

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Intervention Description

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

Intervention Name(s)

Epirubicin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of patients with treatment-related adverse events as assessed by CTCAE v4.0

Time Frame

21 months

Secondary Outcome Measure Information:

Title

Molecular changes in breast

Time Frame

30 months

Title

Pathologic complete response (pCR)

Time Frame

30 months

Title

Clinical complete response (cCR)

Time Frame

21 months

Title

European Organisation for Research and Treatment of Cancer Quality of Life questionnaire C30 (EORTC QOL-C30)

Description

We will consider data related to quality of life such as weakness, appetite, physical health, physiological health, social relationships, environment etc

Time Frame

30 months

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Female sex Ability to give informed agreement and to carry out the whole study protocol during the study period The patient should be able to carry out the needs of the clinical trial and have measurable disease The patient should be 18-75 year-old 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 No previous systemic therapies Patients who are going to benefit from neoadjuvant chemotherapy Eastern Cooperative Oncology Group (ECOG)<2 or Karnofsky≥70% 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: Severe diseases or infectious diseases or liver, kidney or bone marrow failure that advise not to participate in the study according to investigator criteria Pregnancy or breast feeding period or fertility women who are not agree with contraception methods Other primary tumors except for breast in situ carcinoma (CIS), cervical neoplasia(CIN) or localized skin tumors Inflammatory breast cancer or bilateral breast cancer Bone fractures, peptic ulcus or healing disorders Any local or systemic therapy for breast cancer To be maintained on immunosuppressants (prednisone > 10 mgr daily or others), aspirin> 325 mgr per day or clopidogrel > 75 mgr daily 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 Previous lung diseases Personal history of abdominal perforation, abdominal abscess, or abdominal fistula. Inability to swallow pills Intolerance to galactose, malabsorption to galactose or/and glucose, or primary hypolactasia

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Amaya Izal

Phone

+34948255400

Ext

2724

aizal@unav.es

First Name & Middle Initial & Last Name or Official Title & Degree

Joana Reis, Nurse

Phone

+34948255400

Ext

2759

jreis@unav.es

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Santisteban Marta, Doctor

Organizational Affiliation

Staff of the department of Oncology

Official's Role

Principal Investigator

Facility Information:

Facility Name

Clínica Universidad de Navarra

City

Pamplona

State/Province

Navarra

ZIP/Postal Code

31008

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Amaya Izal

Phone

+34948255400

Ext

2724

aizal@unav.es

12. IPD Sharing Statement

Learn more about this trial

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

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