Breast CancerPhase 2NCT02790580
Dose-dense Doxorubicin/Cyclophosphamide With Intermittent Low-dose Sunitinib in Breast Cancer Patients
A Phase 2 study testing Dose-dense doxorubicin/cyclophosphamide + sunitinib and Dose-dense doxorubicin/cyclophosphamide in people with Breast Cancer, run by National University Hospital, Singapore at 1 site in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Dose-dense doxorubicin/cyclophosphamide + sunitinib and Dose-dense doxorubicin/cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 98 participants
- Where
- 1 siteSingapore
- Study dates
- May 2016to Nov 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 with synchronous breast tumors (ipsilateral or bilateral) may be enrolled, provided that none of the tumors is HER2 positive. Protocol-specific biopsy will be performed for each tumor, and each tumor will be assessed separately for pCR rate if the patient is non-metastatic
- Tumor must be HER2 negative by IHC (0 or 1+), or FISH (dual-probe HER2/CEP17 ratio <2.0 with average HER2 copy number <4.0 signals/cell)
- Patients must not have received prior chemotherapy or hormonal therapy for the treatment of breast cancer.
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- ECOG performance 0 or 1.
- 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.
Who cannot join
- 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.
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- 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, with exception of a synchronous HER2 negative breast cancer that is not metastatic
- 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.
Trial locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
National University Hospital, Singapore
Singapore, Singapore, 119228
Soo Chin Lee, (65) 6779 5555, soo_chin_lee@nuhs.edu.sg
About this study
Official title: Dose-dense Doxorubicin/Cyclophosphamide With Intermittent Low-dose Sunitinib as Neoadjuvant or First-line Palliative Treatment of Newly Diagnosed HER2 Negative Breast Cancer Patients With Measurable Primary Breast Tumor
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.
Read the detailed description
Breast cancer is a major cause of morbidity and mortality both locally as well as globally. Approximately 10-15% of newly diagnosed breast cancer patients present with metastatic disease; in addition, a significant proportion of patients who initially present with non-metastatic disease relapse with distant metastases. These patients have no prospect for cure, and systemic therapy remains the mainstay of treatment. In the last few years, several targeted agents have been approved for the treatment of breast cancer. For example, the addition of bevacizumab, an anti-angiogenic agent, to chemotherapy has been shown to improve treatment outcome in metastatic HER2 negative breast cancer and possibly in the neoadjuvant treatment of triple negative breast cancers. Two classes of anti-angiogenic agents are currently available: monoclonal antibodies against vascular endothelial growth factor (VEGF), such as bevacizumab; and small molecule receptor tyrosine kinase inhibitors that target the intracellular tyrosine kinase domain of vascular endothelial growth factor receptor (VEGF-R), such as sunitinib and sorafenib.
Small molecule receptor tyrosine kinase inhibitors such as sunitinib and sorafenib are currently being evaluated in clinical trials. Although sunitinib and sorafenib are potent anti-angiogenic agents, the clinical data that has been reported thus far when combined with chemotherapy, has been less promising than what has been predicted in pre-clinical studies. One possible reason is that optimal scheduling of small molecule tyrosine kinase inhibitors with chemotherapy has not yet been determined. Preclinical observations have suggested that anti-angiogenic agents can 'normalize' tumor vasculature. Further continuous administration of anti-angiogenic agent ultimately results in destruction of tumor vasculature, starving the tumor and resulting in tumor necrosis. When combined with chemotherapy, this continuous scheduling may paradoxically result in reduced delivery of chemotherapy to the tumor, causing a relatively chemo-resistant state and may account for the less than optimal results from combination studies, which have largely employed the strategy of continuous dosing of the small molecule tyrosine kinase inhibitor. Intermittent dosing of a small molecule tyrosine kinase inhibitor prior to chemotherapy to transiently 'normalize' tumor vasculature, may make it more efficient for drug and oxygen delivery, and thus potentiate sensitivity to chemotherapy.
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. The study 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, short-course sunitinib to dose-dense doxorubicin/cyclophosphamide administered every 14 days, supported by pegfilgrastim.
- Conditions
- Breast Cancer
- Being tested
- Dose-dense doxorubicin/cyclophosphamide + sunitinib, Dose-dense doxorubicin/cyclophosphamide
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dose-dense doxorubicin/cyclophosphamide + sunitinibDrug
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.
Dose-dense doxorubicin/cyclophosphamideDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Dose-dense doxorubicin/cyclophosphamide | Active comparator | 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 doxorubicin/cyclophosphamide Receives: Drug: Dose-dense doxorubicin/cyclophosphamide |
| Dose-dense doxorubicin/cyclophosphamide + sunitinib | Experimental | 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) Receives: Drug: Dose-dense doxorubicin/cyclophosphamide + sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical response rate
Measured: Post neoadjuvant chemotherapy (within 2-3 weeks after last dose of neoadjuvant chemotherapy)
Secondary outcomes (2)
Pathological complete response rate
Measured: Post neoadjuvant chemotherapy (within 4-6 weeks after last dose of neoadjuvant chemotherapy)
Progression-free survival
Measured: 2 and 5 year post neoadjuvant chemotherapy/time of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2016 (estimated)
- Study startMay 2016
- Primary completionMay 2020 (estimated)
- Study completionNov 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 98 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Soo Chin Lee, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02790580
- Sponsor's protocol ID
- BR01/01/16
- Other IDs
- 2016/00327, 2016
- Status last verified
- May 2016
- First submitted
- 30 May 2016
- Last updated
- 6 Jun 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Burstein HJ, Elias AD, Rugo HS, Cobleigh MA, Wolff AC, Eisenberg PD, Lehman M, Adams BJ, Bello CL, DePrimo SE, Baum CM, Miller KD. Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2008 Apr 10;26(11):1810-6. doi: 10.1200/JCO.2007.14.5375. Epub 2008 Mar 17.
PubMed 18347007Duda DG, Batchelor TT, Willett CG, Jain RK. VEGF-targeted cancer therapy strategies: current progress, hurdles and future prospects. Trends Mol Med. 2007 Jun;13(6):223-30. doi: 10.1016/j.molmed.2007.04.001. Epub 2007 Apr 25.
PubMed 17462954Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis CA, Winer EP. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015 Jan 1;33(1):13-21. doi: 10.1200/JCO.2014.57.0572. Epub 2014 Aug 4.
PubMed 25092775Choo JRE, Jan YH, Ow SGW, Wong A, Lee MX, Ngoi N, Yadav K, Lim JSJ, Lim SE, Chan CW, Hartman M, Tang SW, Goh BC, Tan HL, Chong WQ, Yvonne ALE, Chan GHJ, Chen SJ, Tan KT, Lee SC. Serial Tumor Molecular Profiling of Newly Diagnosed HER2-Negative Breast Cancers During Chemotherapy in Combination with Angiogenesis Inhibitors. Target Oncol. 2022 May;17(3):355-368. doi: 10.1007/s11523-022-00886-x. Epub 2022 Jun 14.
PubMed 35699834Yadav K, Lim J, Choo J, Ow SGW, Wong A, Lee M, Chan CW, Hartman M, Lim SE, Ngoi N, Tang SW, Ang Y, Chan G, Chong WQ, Tan HL, Tan SH, Goh BC, Lee SC. Immunohistochemistry study of tumor vascular normalization and anti-angiogenic effects of sunitinib versus bevacizumab prior to dose-dense doxorubicin/cyclophosphamide chemotherapy in HER2-negative breast cancer. Breast Cancer Res Treat. 2022 Feb;192(1):131-142. doi: 10.1007/s10549-021-06470-7. Epub 2021 Dec 20.
PubMed 34928481
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose-dense Doxorubicin/Cyclophosphamide With Intermittent Low-dose Sunitinib as Neoadjuvant or First-line Palliative Treatment of Newly Diagnosed HER2 Negative Breast Cancer Patients With Measurable Primary Breast Tumor
- ClinicalTrials.gov ID
- NCT02790580
- Acronym / sponsor ID
- BR01/01/16
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 98 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- May 2016
- Primary completion
- May 2020 (estimated)
- Study completion
- Nov 2020 (estimated)
- First posted
- 6 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Breast cancer is a major cause of morbidity and mortality both locally as well as globally. Approximately 10-15% of newly diagnosed breast cancer patients present with metastatic disease; in addition, a significant proportion of patients who initially present with non-metastatic disease relapse with distant metastases. These patients have no prospect for cure, and systemic therapy remains the mainstay of treatment. In the last few years, several targeted agents have been approved for the treatment of breast cancer. For example, the addition of bevacizumab, an anti-angiogenic agent, to chemotherapy has been shown to improve treatment outcome in metastatic HER2 negative breast cancer and possibly in the neoadjuvant treatment of triple negative breast cancers. Two classes of anti-angiogenic agents are currently available: monoclonal antibodies against vascular endothelial growth factor (VEGF), such as bevacizumab; and small molecule receptor tyrosine kinase inhibitors that target the intracellular tyrosine kinase domain of vascular endothelial growth factor receptor (VEGF-R), such as sunitinib and sorafenib.
Small molecule receptor tyrosine kinase inhibitors such as sunitinib and sorafenib are currently being evaluated in clinical trials. Although sunitinib and sorafenib are potent anti-angiogenic agents, the clinical data that has been reported thus far when combined with chemotherapy, has been less promising than what has been predicted in pre-clinical studies. One possible reason is that optimal scheduling of small molecule tyrosine kinase inhibitors with chemotherapy has not yet been determined. Preclinical observations have suggested that anti-angiogenic agents can 'normalize' tumor vasculature. Further continuous administration of anti-angiogenic agent ultimately results in destruction of tumor vasculature, starving the tumor and resulting in tumor necrosis. When combined with chemotherapy, this continuous scheduling may paradoxically result in reduced delivery of chemotherapy to the tumor, causing a relatively chemo-resistant state and may account for the less than optimal results from combination studies, which have largely employed the strategy of continuous dosing of the small molecule tyrosine kinase inhibitor. Intermittent dosing of a small molecule tyrosine kinase inhibitor prior to chemotherapy to transiently 'normalize' tumor vasculature, may make it more efficient for drug and oxygen delivery, and thus potentiate sensitivity to chemotherapy.
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. The study 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, short-course sunitinib to dose-dense doxorubicin/cyclophosphamide administered every 14 days, supported by pegfilgrastim.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose-dense doxorubicin/cyclophosphamide | Active comparator | Drug: Dose-dense doxorubicin/cyclophosphamideDoxorubicin 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 doxorubicin/cyclophosphamide |
| Dose-dense doxorubicin/cyclophosphamide + sunitinib | Experimental | Drug: Dose-dense doxorubicin/cyclophosphamide + sunitinibDoxorubicin 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) |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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 with synchronous breast tumors (ipsilateral or bilateral) may be enrolled, provided that none of the tumors is HER2 positive. Protocol-specific biopsy will be performed for each tumor, and each tumor will be assessed separately for pCR rate if the patient is non-metastatic
- Tumor must be HER2 negative by IHC (0 or 1+), or FISH (dual-probe HER2/CEP17 ratio <2.0 with average HER2 copy number <4.0 signals/cell)
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dose-dense doxorubicin/cyclophosphamide + sunitinibDoxorubicin 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 + sunitinib |
| Dose-dense doxorubicin/cyclophosphamideDoxorubicin 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. | Drug | Dose-dense doxorubicin/cyclophosphamide |
Primary outcome
Clinical response rate
Time frame: Post neoadjuvant chemotherapy (within 2-3 weeks after last dose of neoadjuvant chemotherapy)
2 secondary outcomes
Pathological complete response rate
Time frame: Post neoadjuvant chemotherapy (within 4-6 weeks after last dose of neoadjuvant chemotherapy)
Progression-free survival
Time frame: 2 and 5 year post neoadjuvant chemotherapy/time of surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2016.
- Background: PubMed 18347007Burstein HJ, Elias AD, Rugo HS, Cobleigh MA, Wolff AC, Eisenberg PD, Lehman M, Adams BJ, Bello CL, DePrimo SE, Baum CM, Miller KD. Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2008 Apr 10;26(11):1810-6. doi: 10.1200/JCO.2007.14.5375. Epub 2008 Mar 17.
- Background: PubMed 17462954Duda DG, Batchelor TT, Willett CG, Jain RK. VEGF-targeted cancer therapy strategies: current progress, hurdles and future prospects. Trends Mol Med. 2007 Jun;13(6):223-30. doi: 10.1016/j.molmed.2007.04.001. Epub 2007 Apr 25.
- Background: PubMed 25092775Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis CA, Winer EP. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015 Jan 1;33(1):13-21. doi: 10.1200/JCO.2014.57.0572. Epub 2014 Aug 4.
- Derived from this study: PubMed 35699834Choo JRE, Jan YH, Ow SGW, Wong A, Lee MX, Ngoi N, Yadav K, Lim JSJ, Lim SE, Chan CW, Hartman M, Tang SW, Goh BC, Tan HL, Chong WQ, Yvonne ALE, Chan GHJ, Chen SJ, Tan KT, Lee SC. Serial Tumor Molecular Profiling of Newly Diagnosed HER2-Negative Breast Cancers During Chemotherapy in Combination with Angiogenesis Inhibitors. Target Oncol. 2022 May;17(3):355-368. doi: 10.1007/s11523-022-00886-x. Epub 2022 Jun 14.
- Derived from this study: PubMed 34928481Yadav K, Lim J, Choo J, Ow SGW, Wong A, Lee M, Chan CW, Hartman M, Lim SE, Ngoi N, Tang SW, Ang Y, Chan G, Chong WQ, Tan HL, Tan SH, Goh BC, Lee SC. Immunohistochemistry study of tumor vascular normalization and anti-angiogenic effects of sunitinib versus bevacizumab prior to dose-dense doxorubicin/cyclophosphamide chemotherapy in HER2-negative breast cancer. Breast Cancer Res Treat. 2022 Feb;192(1):131-142. doi: 10.1007/s10549-021-06470-7. Epub 2021 Dec 20.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Soo Chin Lee principal investigator
National University Hospital, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dose-dense doxorubicin/cyclophosphamide + sunitinib and Dose-dense doxorubicin/cyclophosphamide in people with Breast Cancer, run by National University Hospital, Singapore at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Soo Chin Lee ((65) 6779 5555, soo_chin_lee@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical response rate (time frame: Post neoadjuvant chemotherapy (within 2-3 weeks after last dose of neoadjuvant chemotherapy)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02790580, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2016.