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

NCT01176799 | Unknown Phase 2 DMC

• 1 other identifier: BR01/09/10
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Breast Cancer

Keywords

Breast cancer patients with measurable primary breast cancer tumor.

Outcome Measures

Primary Outcomes (1)

• pathological complete response rate

  To compare the pathological complete response rate of doxorubicin/cyclophosphamide with or without intermittent sunitinib in the first-line pre-operative setting in breast cancer in the Phase II part of the study.

  12 weeks

Secondary Outcomes (1)

• clinical response rate

  12 weeks

Study Arms (2)

Arm A: Control Arm

ACTIVE COMPARATOR

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

Drug: Arm A

Arm B: Experimental

EXPERIMENTAL

Days -13 (or -7) to day 0 (total 7 or 14 days) - oral sunitinib daily 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)

Drug: Arm B

Interventions

Arm A DRUG

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

Also known as: Control Arm, Doxorubicin and Cyclophosphamide

Arm A: Control Arm

Arm B DRUG

Days -13 (or -7) to day 0 (total 7 or 14 days) - oral sunitinib daily 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)

Also known as: Experimental Arm:, Sunitinib and doxorubicin and cyclophosphamide (AC)

Arm B: Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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), vasculitides (e.g., giant cell arteritis, Kawasaki disease, Wegener's granulomatosis, Churg-Strauss disease) or sickle cell disease.

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (2)

National University Hospital

Singapore, Singapore, 119074, Singapore

RECRUITING

National University Hospital

Singapore, Singapore, 119228, Singapore

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; Cyclophosphamide; Sunitinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Soo Chin Lee, MBBS, MRCP

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Soo Chin Lee, MBBS, MRCP

CONTACT

65 6772 4629; Soo_Chin_Lee@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2010
• First Posted: August 6, 2010
• Study Start: August 1, 2010
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2017
• Last Updated: June 22, 2016

Record last verified: 2016-06

Locations

SG (2)