Clinical trial NCT02694224: Addition of Vismodegib to Neoadjuvant Chemotherapy in Triple Negative Breast Cancer Patients
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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Cancer
Keywords: breast cancer
triple negative
neoadjuvant
Lead sponsor: Clinica Universidad de Navarra, Universidad de Navarra
Sponsor class: OTHER
First posted: 2016-02-29
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 21 months
Secondary outcomes:
measure: Molecular changes in breast
timeFrame: 30 months
measure: Pathologic complete response (pCR)
timeFrame: 30 months
measure: Clinical complete response (cCR)
timeFrame: 21 months
measure: European Organisation for Research and Treatment of Cancer Quality of Life questionnaire C30 (EORTC QOL-C30)
timeFrame: 30 months
Other outcomes:
Locations:
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
state: Navarra
Study officials:
affiliation: Staff of the department of Oncology
name: Santisteban Marta, Doctor
role: PRINCIPAL_INVESTIGATOR
References: