Clinical trial NCT01959490
Conditions: Stage II Breast Cancer Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer
Sponsor: Case Comprehensive Cancer Center
Start date: 2013-09-24; Completion date: 2017-03-29
Enrollment: 16 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This phase II trial studies how well trastuzumab and pertuzumab or bevacizumab with combination chemotherapy works in treating patients with stage II-III breast cancer. Monoclonal antibodies, such as trastuzumab, pertuzumab, and bevacizumab, can block tumor growth in different ways. Some block the ability of tumors to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as docetaxel, carboplatin, doxorubicin hydrochloride, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving trastuzumab and pertuzumab or a commercially marketed formulation of bevacizumab without modification with combination chemotherapy may kill more tumor cells.

Detailed description:
PRIMARY OBJECTIVES:

I. To determine if genomically derived 'molecular subtypes' predict pathological complete response to combination chemotherapy and targeted therapy for HER2 early stage breast cancer.

SECONDARY OBJECTIVES:

I. To explore the ability of trastuzumab or pertuzumab response signatures to predict pCR in HER2 positive tumors treated with brief exposure to trastuzumab or pertuzumab followed by combination chemotherapy.

II. To explore the value of immune signatures as well as AKT and IGF signatures to predict pCR in HER2 tumors treated with brief exposure to trastuzumab and pertuzumab.

III. To explore if comprehensive annotation of genomic alterations (mutations, copy number alternations, gene fusions, non-coding RNA and splice variants) can further sub-stratify subtype-based classifiers for prediction of response to targeted therapy in early stage breast cancer IV. To explore if circulating RNA expression levels are associated with treatment response V. To explore changes in cardiac function and identify early cardiac injury using strain echocardiograms and cardiac biomarkers during treatment VI. To explore immunohistochemistry-based markers of response to treatment

Objectives for Imaging Sub-Study: Secondary Objectives I. Evaluate the visualization of primary breast tumors using analog and digital positron emission tomography (PET) with FDG and FLT. II. Evaluate the quantification of FDG-uptake in primary breast tumors using analog and digital PET with FDG and FLT. III. Compare the levels and changes in metabolic tumor activity from analog and digital FDG-PET/CT or FLT-PET/CT with clinical follow up and other procures include into CASE 14112 (such as DCE-MRI, genetic testing, etc.)

OUTLINE: Patients are assigned to 1 of 2 treatment cohorts based on HER2 status.

COHORT I (HER2 positive): Patients receive trastuzumab intravenously (IV) over 30-60 minutes, and pertuzumab IV over 30-60 minutes, docetaxel IV, and carboplatin IV on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. As part of standard of care, each patient will receive three MRIs pre-treatment, before biopsy is taken, and before surgery. Ten additional patients will be added to cohort 1 to take part in the imaging sub-study. These ten patients will follow the same procedure as the other participants in cohort I but will have a PET/CT in place of the DCE-MRI

COHORT II (HER2 negative): Patients receive bevacizumab IV over 30-60 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11; doxorubicin IV and cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 3, 5, and 7; and paclitaxel IV over 3 hours on day 1 of weeks 9, 11, 13, and 15. Prior to receiving paclitaxel patients will receive the anti-nausea medication

After completion of study treatment, patients are followed up for 30 days.

Arms: arm 1: Patients receive a run-in Pertuzumab treatment of 840 mg IV over 60 minutes on day -14 followed by Trastuzumab IV over 30-60 minutes and Pertuzumab IV over 30-60 minutes, docetaxel IV, and carboplatin IV on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. arm 2: Patients receive a run-in Trastuzumab treatment of 8 mg/kg IV over 90 minutes on day -14 followed by Trastuzumab IV over 30-60 minutes and Pertuzumab IV over 30-60 minutes, Docetaxel IV, and Carboplatin IV on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. arm 3: Patients receive Bevacizumab IV over 30-60 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11; Doxorubicin IV and Cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 3, 5, and 7; and Paclitaxel IV over 3 hours on day 1 of weeks 9, 11, 13, and 15.
Interventions: intervention 1: trastuzumab intervention 2: Pertuzumab intervention 3: docetaxel intervention 4: carboplatin intervention 5: doxorubicin intervention 6: cyclophosphamide intervention 7: paclitaxel intervention 8: Bevacizumab
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Given IV intervention 4: Given IV intervention 5: Given IV intervention 6: Given IV intervention 7: Given IV intervention 8: None

Protocol documents: