Phase Ib/II Study of Primary Chemotherapy With Paclitaxel, Gemcitabine, and Sunitinib

• Status: Completed
• Trial end date: 2010-11-01
• Target enrollment: 0
• Participant gender: Female

Summary

Phase Ib part:

▪ Primary objective: To demonstrate the recommended dose of the combination of paclitaxel, gemcitabine, and sunitinib (sutene®) (PGS) as preoperative chemotherapy in patients with HER2-negative operable breast cancer

• Secondary objective:

1. To demonstrate the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of this regimen

2. To determine the safety profile

Phase II part

• Primary objective:

To evaluate the pathologic complete response rate (pCR) to preoperative administration of PGS

▪ Secondary objective:

1. To assess breast conserving rate after preoperative PGS

2. To evaluate clinical response rate, disease free survival (DFS), and overall survival (OS)

3. To assess the safety profiles of PGS

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jungsil Ro
• Collaborators: CJ HealthCare Corporation; HK inno.N Corporation; Pfizer
• Treatments: Albumin-Bound Paclitaxel; Gemcitabine; Paclitaxel; Sunitinib

Criteria

Inclusion Criteria:

1. Age ≥ 18 years

2. ECOG performance status 0-2

3. Histologically confirmed and newly diagnosed breast cancer

4. Documented HER2/neu non-overexpressing or non-amplified disease

• 0-1+ by HER2 IHC or

• HER2 gene non-amplification by HER2 FISH

5. Clinical stage II or III operable breast cancer

6. Axillary node positivity determined by cytology

7. No prior hormonal, chemotherapy or radiotherapy is allowed

8. No breast operation other than biopsy to make diagnosis is allowed

9. Adequate hematologic, hepatic and renal function

• Absolute neutrophil count ≥ 1,500/μL

• Hemoglobin ≥ 10.0 g/dL

• Platelet ≥ 100,000/μL

• AST/ALT ≤ 2 X UNL (upper limit of normal)

• Total bilirubin ≤ 1.5 mg/dL

• Alkaline phosphatase ≤ 2 X UNL

• Serum creatinine ≤ 1.5 mg/dL

10. Adequate cardiac function LVEF ≥ 50% and within the institutional range of normal as measured by echocardiogram or MUGA scan within 4 weeks of enrollment

11. Women of childbearing potential must have a negative urine pregnancy test within 7 days prior to registration

12. Normal mental function to understand and sign the consent

Exclusion Criteria:

1. Patients with metastatic breast cancer

2. Patients who received hormonal, chemotherapy or radiotherapy for breast cancer

3. Patients who underwent surgery for breast cancer

4. Patients with T2N0, or inflammatory (T4d) breast cancer

5. Patients who have history of cancer other than in situ uterine cervix cancer or nonmelanotic skin cancer

6. Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis)

7. Any of the following within the 12 months prior to starting study treatment

• severe, unstable angina

• Myocardial infarction

• Uncontrolled or symptomatic congestive heart failure

• coronary/peripheral artery bypass graft

• cerebrovascular accident including transient ischemic attack

• pulmonary embolism

8. Ongoing cardiac dysrhythmias of grade ≥2, atrial fibrillation of any grade, or QTc interval >470 msec.

9. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy)

10. Current treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg po daily for deep vein thrombosis prophylaxis is allowed).

11. Known HIV infection

12. Pregnancy or breastfeeding. Female patients who are pregnant or nursing, female of child-bearing potential who is unwilling to use adequate contraception to prevent pregnancy during the program. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to study entry.

13. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug during administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.