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

Breast Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02694224
• Other study ID #: SHH (Sonic HedgeHog)-CM
• Status: Recruiting
• Phase: Phase 2
• First received: January 12, 2016
• Last updated: October 23, 2017
• Start date: April 2016
• Est. completion date: December 2018

Study information

• Verified date: October 2017
• Source: Clinica Universidad de Navarra, Universidad de Navarra
• Contact: Amaya Izal
• Phone: +34948255400
• Email: aizal[@]unav.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• vismodegib
Smo inhibitor
• 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
• Epirubicin
dose dense Epirubicin (90 mg/m2) plus Cyclophosphamide each 2 weeks x 4 doses with GMCSF after Paclitaxel
• Cyclophosphamide
dose dense Cyclophosphamide (600 mg/m2) together with Epirubicin each 2 weeks x 4 doses with GMCSF after Paclitaxel

Locations

Country	Name	City	State
Spain	Clínica Universidad de Navarra	Pamplona	Navarra

Sponsors (1)

Lead Sponsor	Collaborator
Clinica Universidad de Navarra, Universidad de Navarra

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with treatment-related adverse events as assessed by CTCAE v4.0		21 months
Secondary	Molecular changes in breast		30 months
Secondary	Pathologic complete response (pCR)		30 months
Secondary	Clinical complete response (cCR)		21 months
Secondary	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	30 months