Phase I/II Trial of Neoadjuvant Sunitinib Administered With Weekly Paclitaxel/Carboplatin in Patients With Locally Advanced Triple-Negative Breast Cancer
Overview
- Phase
- Phase 1
- Intervention
- Paclitaxel
- Conditions
- Breast Cancer
- Sponsor
- SCRI Development Innovations, LLC
- Enrollment
- 54
- Locations
- 14
- Primary Endpoint
- Phase II: The Number of Subjects Exhibiting Pathologic Complete Response to Neoadjuvant Treatment With Sunitinib/Paclitaxel/Carboplatin
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This trial will examine the combination of sunitinib plus paclitaxel and carboplatin as neoadjuvant treatment for locally advanced breast cancer.
Detailed Description
This open label, Phase I/II trial is designed to evaluate the combination of sunitinib plus paclitaxel and carboplatin as neoadjuvant treatment for locally advanced breast cancer. The Phase I portion of this study will determine the maximum tolerated dose (MTD) of paclitaxel, sunitinib and carboplatin that can be used together as neoadjuvant treatment in patients with locally advanced breast cancer. The MTD identified in the Phase I portion of the study will be used in the Phase II portion which will evaluate the efficacy, safety, and tolerability of neoadjuvant sunitinib/paclitaxel/carboplatin given for 6 cycles in patients with locally advanced breast cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female patients, age ≥18 years
- •Histologically confirmed invasive ER-, PR-, and HER2-negative (triple-negative) adenocarcinoma of the breast
- •Triple-negative tumors are defined as:
- •For HER2-negative:
- •Fluorescence in situ hybridization (FISH)-negative (defined by ratio \<2.2) OR
- •Immunohistochemical (IHC) 0, IHC 1+, OR
- •IHC 2+ or IHC 3+ and FISH-negative (defined by ratio \<2.2)
- •For ER- and PR-negative: \<10% tumor staining by immunohistochemistry (IHC)
- •Primary palpable disease confined to a breast and axilla on physical examination. For patients without clinically suspicious axillary adenopathy, the primary tumor must be larger than 2 cm in diameter by physical exam or imaging studies (clinical T2-T3, N0-N1, M0). For patients with clinically suspicious axillary adenopathy, the primary breast tumor can be any size (clinical T1-3, N1-2, M0). T1N0M0 lesions are excluded. Patients with metastatic disease are excluded.
- •Patients without clearly defined palpable breast mass or axillary lymph nodes but radiographically measurable tumor masses are eligible. Accepted procedures for measuring breast disease are mammography, MRI, and breast ultrasound. Patients with lesions measurable only by imaging will require repeat imaging after 3 cycles and prior to surgery
Exclusion Criteria
- •Previous treatment for this breast cancer
- •Previous treatment with paclitaxel or carboplatin
- •Previous treatment with sunitinib or other angiogenic inhibitors (including, but not limited to bevacizumab, sorafenib, thalidomide)
- •Any of the following within the 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolus
- •Uncontrolled hypertension (blood pressure \>150/100 mmHg despite optimal medical therapy)
- •Ongoing cardiac dysrhythmias grade ≥2, atrial fibrillation of any grade, or prolongation of the QTc interval to \>470 msec
- •Major surgery, significant traumatic injury, or radiation therapy within 4 weeks of starting study treatment. An interval of at least 1week is required following minor surgical procedures, with the exception of placement of a vascular access device
- •Grade 3 hemorrhage within 4 weeks of starting study treatment
- •Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
- •Known human immunodeficiency virus (HIV) infection or other serious infection
Arms & Interventions
Dose Level I
Neoadjuvant - Paclitaxel IV (70 mg/m\^2) days 1, 8 and 15 of each cycle, Carboplatin IV (AUC = 5) day 1 of every cycle and Sunitinib PO (25mg) daily. Maintenance - Sunitinib PO (25mg) daily
Intervention: Paclitaxel
Dose Level I
Neoadjuvant - Paclitaxel IV (70 mg/m\^2) days 1, 8 and 15 of each cycle, Carboplatin IV (AUC = 5) day 1 of every cycle and Sunitinib PO (25mg) daily. Maintenance - Sunitinib PO (25mg) daily
Intervention: Carboplatin
Dose Level I
Neoadjuvant - Paclitaxel IV (70 mg/m\^2) days 1, 8 and 15 of each cycle, Carboplatin IV (AUC = 5) day 1 of every cycle and Sunitinib PO (25mg) daily. Maintenance - Sunitinib PO (25mg) daily
Intervention: Sunitinib
Dose Level II
Paclitaxel IV (80 mg/m\^2) days 1, 8 and 15 of each cycle, Carboplatin IV (AUC = 5) day 1 of every cycle and Sunitinib PO (25mg) daily.
Intervention: Paclitaxel
Dose Level II
Paclitaxel IV (80 mg/m\^2) days 1, 8 and 15 of each cycle, Carboplatin IV (AUC = 5) day 1 of every cycle and Sunitinib PO (25mg) daily.
Intervention: Carboplatin
Dose Level II
Paclitaxel IV (80 mg/m\^2) days 1, 8 and 15 of each cycle, Carboplatin IV (AUC = 5) day 1 of every cycle and Sunitinib PO (25mg) daily.
Intervention: Sunitinib
Dose Level III
Paclitaxel IV (80 mg/m\^2) days 1, 8 and 15 of each cycle, Carboplatin IV (AUC = 6) day 1 of every cycle and Sunitinib PO (25mg) daily.
Intervention: Paclitaxel
Dose Level III
Paclitaxel IV (80 mg/m\^2) days 1, 8 and 15 of each cycle, Carboplatin IV (AUC = 6) day 1 of every cycle and Sunitinib PO (25mg) daily.
Intervention: Carboplatin
Dose Level III
Paclitaxel IV (80 mg/m\^2) days 1, 8 and 15 of each cycle, Carboplatin IV (AUC = 6) day 1 of every cycle and Sunitinib PO (25mg) daily.
Intervention: Sunitinib
Outcomes
Primary Outcomes
Phase II: The Number of Subjects Exhibiting Pathologic Complete Response to Neoadjuvant Treatment With Sunitinib/Paclitaxel/Carboplatin
Time Frame: at weeks 26-30
Pathologic complete response (PCR) is defined as no residual invasive breast cancer in final breast or axillary lymph node samples.
Secondary Outcomes
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability(Days 1, 8, and 15 of each 4-week cycle up to 24 weeks during neoadjuvant treatment, and every 4 weeks during maintenance treatment)
- Overall Response Rate (ORR)(Days 1, 8 and 15 of each cycle, minimum of 12 weeks)
- Disease-free Survival(every 4 weeks from date of surgery until treatment discontinuation or death, expected average 18 months)
- Overall Survival (OS)(24 months)