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

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

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

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: vismodegib; Drug: Paclitaxel; Drug: Epirubicin; Drug: Cyclophosphamide

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Recruiting
      • Clinica Universidad de Navarra
      • Contact: Amaya Izal; Phone Number: 2724 +34948255400; Email: aizal@unav.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vismodegib plus chemotherapy; Vismodegib 150 mg orally during paclitaxel and then dose dense epirubicin + cyclophosphamide (EC) therapy (see active comparator arm)	Drug: vismodegib; Smo inhibitor; Other Names: GDC0449; 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; Drug: Epirubicin; dose dense Epirubicin (90 mg/m2) plus Cyclophosphamide each 2 weeks x 4 doses with GMCSF after Paclitaxel; Drug: Cyclophosphamide; dose dense Cyclophosphamide (600 mg/m2) together with Epirubicin each 2 weeks x 4 doses with GMCSF after Paclitaxel
Active Comparator: 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	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; Drug: Epirubicin; dose dense Epirubicin (90 mg/m2) plus Cyclophosphamide each 2 weeks x 4 doses with GMCSF after Paclitaxel; Drug: Cyclophosphamide; dose dense Cyclophosphamide (600 mg/m2) together with Epirubicin each 2 weeks x 4 doses with GMCSF after Paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patients with treatment-related adverse events as assessed by CTCAE v4.0	21 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular changes in breast		30 months
Pathologic complete response (pCR)		30 months
Clinical complete response (cCR)		21 months
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

Collaborators and Investigators

• Sponsor: Clinica Universidad de Navarra, Universidad de Navarra
• Investigators: Principal Investigator: Santisteban Marta, Doctor, Staff of the department of Oncology

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: January 12, 2016
• First Submitted That Met QC Criteria: February 23, 2016
• First Posted (Estimate): February 29, 2016

Study Record Updates

• Last Update Posted (Actual): October 24, 2017
• Last Update Submitted That Met QC Criteria: October 23, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: breast cancer; neoadjuvant; triple negative
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Paclitaxel; Epirubicin
• Other Study ID Numbers: SHH (Sonic HedgeHog)-CM