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

This study is currently recruiting participants.
Verified January 2014 by National University Hospital, Singapore
Sponsor:
Information provided by:
National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT01176799
First received: August 5, 2010
Last updated: January 21, 2014
Last verified: January 2014
  Purpose

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 total of fifty patients with measurable primary tumor will be enrolled over a period of 18-24 months. 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 to day 0 (total 14 days) - oral sunitinib 37.5mg daily Cycle 1: day 1 - Cycle 1 AC (60/600mg/m2); days 15-21 - oral sunitinib 37.5mg daily Cycle 2: day 1 - Cycle 2 AC (60/600mg/m2); days 15-21 - oral sunitinib 37.5mg daily Cycle 3: day 1 - Cycle 3 AC (60/600mg/m2); days 15-21 - oral sunitinib 37.5mg daily Cycle 4: day 1 - Cycle 4 AC (60/600mg/m2)

Imaging studies

DCE-MRI

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

Arm A: At baseline (before cycle 1 AC) and once at mid-cycle of cycle 1 (days 12-14). Arm B: At baseline (before sunitinib), after completing at least 12 days of sunitinib and before cycle 1 AC, and during mid-cycle of cycle 1 AC (days 12-14 following cycle 1 AC).

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.

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 after 7 days and 14 days 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, including VEGF-A, VEGF-C, soluble VEGF receptors (sVEGFR-1, sVEGFR-2, sVEGFR-3), placental derived growth factor (PIGF), soluble inter-cellular adhesion molecule 1 (sICAM-1), Tie-2 and stromal derived factor 1a (SDF-1a). Samples will be taken at baseline and every week during cycle 1 AC, followed by every 3 weeks prior to each subsequent cycle of AC. One sample will be taken within 4 weeks of completing 4 cycles of AC, within 4 weeks after surgery, followed by 4-monthly until disease progression. Patients in Arm B will have additional two samples taken on a weekly basis during the first two weeks of sunitinib.

Serial whole blood for gene expression analysis at baseline and 2 weeks after cycle 1 AC for all patients, and after completing at least 12 days of sunitinib and prior to cycle 1 AC for subjects in Arm B.

Serial blood samples for circulating tumor and circulating endothelial cells at baseline and every 3 weeks during the four cycles of AC. Patients in Arm B will have an additional sampling for circulating tumor and circulating endothelial cells after completing at least 12 days of sunitinib and before cycle 1 AC.

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 at least 12 days of sunitinib and before cycle 1 AC, approximately 3 MainPrint Page 3 of 23 https://www.b2bresearch.nhg.com.sg/DSRB/DSRBWeb/Protocols/MainPrint.aspx 06/05/2010 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.


Condition Intervention Phase
Breast Cancer
Drug: Doxorubicin, Cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National University Hospital, Singapore:

Estimated Enrollment: 50
Study Start Date: August 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female, age >= 18 years.
  • Histologic or cytologic diagnosis of breast carcinoma.
  • T2-4 breast cancer with measurable primary breast tumor, defined as palpable tumor with both diameters 2.0cm or greater as measured by caliper.
  • Patients must not have received prior chemotherapy or hormonal therapy for the treatment of breast cancer.
  • Karnofsky performance status of 70 or higher.
  • Estimated life expectancy of at least 12 weeks.
  • Adequate organ function including the following:

    • Bone marrow:
  • Absolute neutrophil (segmented and bands) count (ANC) >=1.5 x 109/L
  • Platelets >= 100 x 109/L

    • Hepatic:
  • Bilirubin <= 1.5 x upper limit of normal (ULN),
  • ALT or AST <= 2.5x ULN, (or <= 5 X with liver metastases)

    • Renal:
  • Creatinine <= 1.5x ULN
  • Left ventricular ejection fraction >=50%
  • Signed informed consent from patient or legal representative.
  • Patients with reproductive potential must use an approved contraceptive method if appropriate (e.g., intrauterine device, birth control pills, or barrier device) during and for three months after the study.Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.

Exclusion Criteria:

  • Prior treatment for locally advanced or metastatic breast cancer.
  • Treatment within the last 30 days with any investigational drug.
  • Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
  • Major surgery within 28 days of study drug administration.
  • Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
  • Pregnancy.
  • Breast feeding.
  • Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
  • Active bleeding disorder or bleeding site.
  • Non-healing wound.
  • Poorly controlled diabetes mellitus.
  • Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
  • Symptomatic brain metastasis.
  • History of significant neurological or mental disorder, including seizures or dementia.
  • Known history of systemic connective tissue diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis), vasculitidies (e.g., giant cell arteritis, Kawasaki disease, Wegener's granulomatosis, Churg-Strauss disease) or sickle cell disease.
  • Known history of renal impairment, defined as a Glomerular Filtration Rate (GFR) of less than 30ml/minute.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01176799

Contacts
Contact: Soo Chin Lee, MBBS, MRCP 65 6772 4629 Soo_Chin_Lee@nuhs.edu.sg

Locations
Singapore
National University Hospital Recruiting
Singapore, Singapore, 119074
Contact: Soo Chin Lee, MBBS, MRCP    65 6772 4629    Soo_Chin_Lee@nuhs.edu.sg   
Principal Investigator: Soo Chin Lee, MBBS, MRCP         
National University Hospital Recruiting
Singapore, Singapore, 119228
Sponsors and Collaborators
National University Hospital, Singapore
Investigators
Principal Investigator: Soo Chin Lee, MBBS, MRCP National University Hospital, Singapore
  More Information

No publications provided

Responsible Party: National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT01176799     History of Changes
Other Study ID Numbers: BR01/09/10
Study First Received: August 5, 2010
Last Updated: January 21, 2014
Health Authority: Singapore: Domain Specific Review Boards

Keywords provided by National University Hospital, Singapore:
Breast cancer patients with measurable primary breast cancer tumor.

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Sunitinib
Doxorubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on April 15, 2014