Dose-dense Doxorubicin/Cyclophosphamide With Intermittent Low-dose Sunitinib in Breast Cancer Patients
Status:
Unknown status
Trial end date:
2020-11-01
Target enrollment:
Participant gender:
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.