Randomized Study of Doxorubicin and Cyclophosphamide With or Without Intermittent Sunitinib in the First-line Treatment of Locally Advanced or Metastatic Breast Cancer Patients With Measurable Primary Breast Tumor

Breast Cancer Clinical Trial

Official title: Phase II Randomized Study of Doxorubicin and Cyclophosphamide With or Without Intermittent Sunitinib in the First-line Treatment of Locally Advanced or Metastatic Breast Cancer Patients With Measurable Primary Breast Tumor

Status Recruiting

Clinical Trial Summary

This is a single-centre, phase II randomized study of doxorubicin and cyclophosphamide (AC) with or without intermittent sunitinib in patients with measurable primary breast cancer who are receiving pre-operative chemotherapy.

A lead-in phase I study was built into this protocol to determine the dose and duration of sunitinib that may achieve the desired effects of normalizing tumor vasculature prior to chemotherapy administration.

A total of 64 patients with measurable primary tumor will be enrolled for the Phase II part of the study. Eligible patients will be randomized 1:1 to either arm A or arm B. Patients will be stratified according to metastatic status (metastatic vs non-metastatic) and presence or absence of clinical T4 disease.

Arm A (Control arm):

Doxorubicin 60mg/m2 day 1 Cyclophosphamide 600mg/m2 day1, every 3 weeks x 4 cycles

Arm B (Experimental arm):

Days -13 (or -7) to day 0 (total 7 or 14 days) - oral sunitinib daily (duration and dose as determined from the lead-in phase I study) Cycle 1: day 1 - Cycle 1 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 2: day 1 - Cycle 2 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 3: day 1 - Cycle 3 AC (60/600mg/m2); days 15-21 - oral sunitinib daily Cycle 4: day 1 - Cycle 4 AC (60/600mg/m2)

DCE-MRI scan will be performed serially to determine tumor response and change in tumor vascular parameters for each enrolled subject:

Patient will be evaluated weekly for toxicity assessments and full blood count during cycle 1, and on days 1 and 15 of each subsequent cycle. In addition, patients in Arm B will be evaluated weekly during the first two weeks of sunitinib administration prior to cycle 1 AC.

Clinical Trial Description

Special tests Blood sampling

• Germline DNA at baseline for pharmacogenetics analysis.

• Pharmacokinetic sampling for doxorubicin and cyclophosphamide on day 1, cycle 1 of AC administration.

• Pharmacokinetic sampling for sunitinib at baseline and weekly during the first course of sunitinib for subjects in Arm B before the sunitinib dose on that day.

• Serial plasma samples for proteomics analysis and for analysis of soluble angiogenic factors

• Serial whole blood for gene expression analysis

• Serial blood samples for circulating tumor and circulating endothelial cells

• DNA will be extracted from collected snap-frozen and/or paraffin-embedded tumor tissue sections (pre- and post-treatment) and plasma (pre- and post-treatment taken for plasma biomarker analysis). Primary tumor and circulating tumor DNA will be genotyped for cancer genes of interest that may influence cancer prognosis and/or treatment response.

Tumor core biopsy Arm A: Performed at baseline, approximately 3 weekly after cycle 1 AC but before cycle 2 AC, and upon completion of 4 cycles of AC, for a total of 3 tumor core biopsies Arm B: Performed at baseline, after completing the first course of sunitinib and before cycle 1 AC, approximately 3 weekly after cycle 1 AC but before cycle 2 AC, and upon completion of 4 cycles of AC, for a total of 4 tumor core biopsies.

The final biopsy may be obtained at surgery if the patient is scheduled for lumpectomy or mastectomy. The tumor cores will be stored in liquid nitrogen for subsequent DNA, RNA and protein extraction for biomarker studies including gene expression and proteomics analyses. Three to four samples will be obtained at each time point, and one tumor core at each time point will be stored in formalin and paraffin-embedded for immunohistochemistry analysis of biomarkers.

Note: Tumor biopsies, imaging and blood collection that are to be conducted after completing the first course of sunitinib may be carried out as early as 2 days before the last dose of sunitinib in the first course for logistics reasons. ;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

• NCT number: NCT01176799
• Study type: Interventional
• Source: National University Hospital, Singapore
• Contact: Soo Chin Lee, MBBS, MRCP
• Phone: 65 6772 4629
• Email: Soo_Chin_Lee@nuhs.edu.sg
• Status: Recruiting
• Phase: Phase 2
• Start date: August 2010
• Completion date: December 2017