Neoadjuvant Sunitinib With Paclitaxel/Carboplatin in Patients With Triple-Negative Breast Cancer

NCT00887575 | Completed Phase 1 Results

• 1 other identifier: SCRI BRE 122
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 14

Brief Summary

This trial will examine the combination of sunitinib plus paclitaxel and carboplatin as neoadjuvant treatment for locally advanced breast cancer.

Conditions

Breast Cancer

Keywords

Breast Cancer; Triple-Negative; Paclitaxel; Carboplatin; Sunitinib; Sutent; Neoadjuvant

Outcome Measures

Primary Outcomes (1)

• Phase II: The Number of Subjects Exhibiting Pathologic Complete Response to Neoadjuvant Treatment With Sunitinib/Paclitaxel/Carboplatin

  Pathologic complete response (PCR) is defined as no residual invasive breast cancer in final breast or axillary lymph node samples.

  at weeks 26-30

Secondary Outcomes (4)

• 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

Study Arms (3)

Dose Level I

EXPERIMENTAL

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

Drug: Paclitaxel; Drug: Carboplatin; Drug: Sunitinib

Dose Level II

EXPERIMENTAL

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.

Drug: Paclitaxel; Drug: Carboplatin; Drug: Sunitinib

Dose Level III

EXPERIMENTAL

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.

Drug: Paclitaxel; Drug: Carboplatin; Drug: Sunitinib

Interventions

Paclitaxel DRUG

IV infusion per institutional guidelines on Days 1, 8 and 15 of a 28 day cycle as follows depending on dose level (DL): DL1- 70 mg/m2, DL2- 80 mg/m2, DL3- 80mg/m2, DL4- 80mg/m2, DL-1- 70mg/m2, DL-2- 60mg/m2

Also known as: Taxol, Systemic Therapy

Dose Level I; Dose Level II; Dose Level III

Carboplatin DRUG

IV infusion per institutional guidelines Day 1 of a 28 day cycle as follows depending on dose level (DL): DL1- AUC=5, DL2- AUC=5, DL3- AUC=6, DL4- AUC=6, DL-1- AUC=4, DL-2- AUC=4

Also known as: Paraplatin, Systemic Therapy

Dose Level I; Dose Level II; Dose Level III

Sunitinib DRUG

By mouth (PO) once daily on days 1-21 of a 28 day cycle as follows depending on dose level (DL): DL1- 25mg, DL2-25mg, DL3- 25mg, DL4- 37.5mg, DL-1- 25mg, DL-2- 25mg. Maintenance therapy of 25mg daily

Also known as: Sutent, Systemic Therapy

Dose Level I; Dose Level II; Dose Level III

Eligibility Criteria

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

You may qualify if:

• 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
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2
• Neuropathy grade \<1 by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v 3.0)
• Resolution of all acute effects of surgical procedures to grade ≤1.
• For patients who had, or will have sentinel lymph node and/or axillary dissection prior to initiation of study treatment, completion at least 4 weeks prior to starting study treatment and well-healed wound is required
• Adequate hematologic function with:

You may not qualify if:

• 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
• Concomitant treatment with drugs having proarrhythmic potential including terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, and flecainide
• Concurrent use of the potent CYP3A4 inhibitors ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine and voriconazole and CYP3A4 inducers rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, St. John's Wort, and dexamethasone. Use of dexamethasone for study premedication is allowed. Grapefruit and grapefruit juice is prohibited. Alternative therapies should be used when available. If use of a potent CYP3A4 inhibitor or inducer is necessary, this must be approved by the Study Chair
• Known or suspected hypersensitivity to drugs containing Cremophor®EL (polyoxyethylated castor oil) such as cyclosporine or teniposide
• Pregnancy or breast-feeding. Negative serum pregnancy test is required within 7 days prior to first study treatment (Day 1, Cycle ) for all women of childbearing potential. Patients of childbearing potential must agree to use a birth control method that is approved by their study physician while receiving study treatment and for three months after the last dose of study treatment. Patients must agree to not breast-feed while receiving study treatment
• Concurrent treatment with an ovarian hormonal replacement therapy or with hormonal agents such as raloxifene, tamoxifen or other selective estrogen receptor modulator (SERM). Patients must have discontinued use of such agents prior to beginning study treatment

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Pfizer: collaborator

Study Sites (14)

Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

Florida Cancer Specialists North

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Specialists South

Fort Myers, Florida, 33916, United States

Location

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

Location

Providence Medical Group

Terre Haute, Indiana, 47802, United States

Location

Baptist Hospital East

Louisville, Kentucky, 40207, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

National Capital Clinical Research Consortium

Bethesda, Maryland, 20817, United States

Location

St. Louis Cancer Care

Chesterfield, Missouri, 63017, United States

Location

Nebraska Methodist Cancer Center

Omaha, Nebraska, 68114, United States

Location

Hematology Oncology Associates of Northern NJ

Morristown, New Jersey, 07960, United States

Location

Cancer Centers of Southwest Oklahoma

Lawton, Oklahoma, 73505, United States

Location

Family Cancer Center

Collierville, Tennessee, 38017, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; Carboplatin; Sunitinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: John D. Hainsworth, MD
• Organization: Sarah Cannon Research Institute

asksarah@scresearch.net

1-877-691-7274

Study Officials

• Denise A Yardley, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2009
• First Posted: April 24, 2009
• Study Start: June 1, 2009
• Primary Completion: July 1, 2013
• Study Completion: September 1, 2014
• Last Updated: September 7, 2016
• Results First Posted: December 17, 2014

Record last verified: 2016-09

Locations

US (14)