Dose-dense Doxorubicin/Cyclophosphamide With Intermittent Low-dose Sunitinib in Breast Cancer Patients

Summary

Background: The investigators previously studied the addition of low-dose, short-course sunitinib to pre-operative chemotherapy in the neoadjuvant setting in newly diagnosed breast cancer patients with measurable primary breast tumor in a phase Ib/II study at the National University Cancer Institute, Singapore. These data showed that the addition of sunitinib improved tumor vascularization as hypothesized with enhanced short-term treatment response. However, pathological complete response rate after 4 cycles of chemotherapy was not superior to standard chemotherapy, and may be attributed to dose delays from increased myelosuppression with the addition of sunitinib. The investigators hypothesize that this promising regimen may be further optimized with the use of growth factor support. The investigators thus plan to study the addition of low-dose, shortcourse sunitinib to dose-dense doxorubicin/cyclophosphamide (ddAC) administered every 14 days, supported by pegfilgrastim.

Aim: To confirm that the addition of 12.5mg sunitinib for 5-7 days can be added before each cycle of ddAC (delivered every 14 days, supported by pegfilgrastim) without compromising dose intensity, in phase II open label single arm part of the study, followed by a phase II randomized study to compare the pathological complete response rate of ddAC versus sunitinib + ddAC in stage I-III HER2 negative breast cancer patients in the neoadjuvant setting.

Methods:A single-centre study comprising two phases: a. Phase II open label single-arm study that will enroll newly diagnosed stage I-IV HER2 negative breast cancer patients receiving either neoadjuvant chemotherapy (stage I-III patients) or first-line palliative chemotherapy (stage IV patients). All patients will be treated with 4 cycles of ddAC at standard doses (60/600mg/m2) every 2 weeks, supported by subcutaneous pegfilgrastim 6mg, to be administered 24-36 hours after each dose of chemotherapy. Low dose sunitinib at 12.5mg daily orally will be administered for 7 days prior to cycle 1 ddAC, and for 5 days prior to each subsequent cycle of ddAC. b. Phase II randomized study that will enroll newly diagnosed stage I-III HER2 negative breast cancer patients receiving neoadjuvant chemotherapy before definitive breast cancer surgery. Eligible patients will be randomized 1:1 to 4 cycles of ddAC with or without intermittent sunitinib in patients with measurable primary breast cancer who are receiving preoperative chemotherapy.

Conditions

• Breast Cancer

Interventions

DRUG

Dose-dense doxorubicin/cyclophosphamide + sunitinib

Doxorubicin 60mg/m2 day 1, every 2 weeks x 4 cycles Cyclophosphamide 600mg/m2 day1, every 2 weeks x 4 cycles Subcutaneous pegfilgrastim 6mg, 24-36 hours after each cycle of doxorubicin/cyclophosphamide Oral sunitinib 12.5mg daily for 7 days prior to cycle 1 ddAC (days -7 to 0) Oral sunitinib 12.5mg daily for 5 days prior to cycle 2, 3, 4 ddAC (days 10-14 of preceding cycle) Lumpectomy or mastectomy with sentinel lymph node biopsy or axillary lymph node clearance as appropriate should be considered after completing four cycles of chemotherapy for curative intent in non-metastatic patients and for local control for patients with metastatic disease.

DRUG

Dose-dense doxorubicin/cyclophosphamide

Doxorubicin 60mg/m2 day 1, every 2 weeks x 4 cycles Cyclophosphamide 600mg/m2 day1, every 2 weeks x 4 cycles Subcutaneous pegfilgrastim 6mg, 24-36 hours after each cycle of doxorubicin/cyclophosphamide Lumpectomy or mastectomy with sentinel lymph node biopsy or axillary lymph node clearance as appropriate should be considered after completing four cycles of chemotherapy for curative intent in non-metastatic patients and for local control for patients with metastatic disease.

Sponsors & Collaborators

• National University Hospital, Singapore

  lead OTHER

Principal Investigators

• Soo Chin Lee · National University Hospital, Singapore

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

99 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-05-31

Primary Completion

2020-05-31

Completion

2020-11-30

Countries

• Singapore

Study Locations