Study of Neoadjuvant Chemotherapy With Nanoparticle Albumin Bound Paclitaxel, Doxorubicin and Cyclophosphamide (NAC) in Patients With Stages II-III Breast Cancer (NAC)

Phase I Study of Neoadjuvant Chemotherapy With Nanoparticle Albumin Bound Paclitaxel, Doxorubicin and Cyclophosphamide (NAC) in Patients With Stages II-III Breast Cancer

The purpose of this clinical trial is to test whether treatment of patients with breast cancer with the combination of Abraxane (nab-paclitaxel), Adriamycin (doxorubicin), and Cyclophosphamide prior to surgery is safe and results in good tumor response. Up to 24 patients may be enrolled in this study at the Mitchell Cancer Institute. All patients enrolling in this study will receive treatment with the combination of Abraxane, Adriamycin, and Cyclophosphamide.

Study Overview

• Status: Terminated
• Conditions: Stages II-III Breast Cancer
• Intervention / Treatment: Drug: Nanoparticle Albumin Bound Paclitaxel; Drug: doxorubicin; Drug: cyclophosphamide

Detailed Description

This is a single center, open phase I dose escalation study with expansion cohort. The dose escalation part of the study is now closed and the highest tolerable dose of nab-paclitaxel (Abraxane) was assessed to be 100 mg/m2 in combination with doxorubicin (Adriamycin) and cyclophosphamide in patients with stages II-III breast cancer in the neoadjuvant setting. The initial phase I study objective was to primarily assess the safety of the drug combination, and to secondarily obtain preliminary data on the clinical efficacy of the combination. 25 patients were enrolled. The expansion cohort will enroll 15 additional patients.

The purpose of the expansion cohort is to assess pathological complete response.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Histologically or cytologically proven adenocarcinoma of the breast stages II-III, according to the AJCC Staging Manual, 7th Edition, 2009

2. The following receptor status:

   Expansion: Triple negative (ER<1%, PR<1%, and Her-2/neu negative Phase 1 (closed): Negative Her-2/neu status

3. ECOG performance status 0 or 1
4. Negative pregnancy test
5. Normal cardiac function (ejection fraction > lower limit of normal) as determined by MUGA or echocardiogram
6. ANC greater than or equal to 1,500/mm3; platelet greater than or equal to 100,000/mm3; hemoglobin greater than or equal to 9 gm/dL
7. Serum bilirubin levels less than or equal to 1.5 mg/dL
8. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) less than or equal to 2.5 X upper limit of normal, alkaline phosphatase less than or equal to 2.5 X upper limit of normal.
9. Serum creatinine levels less than or equal to 1.5 mg/dL
10. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with nab-paclitaxel through 28 days after the last dose. Men should be advised to not father a child while receiving treatment with azacitidine or nab-paclitaxel. Appropriate methods of birth controls for women include oral or implanted contraceptives, intrauterine device (IUD), diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner and also based on the judgment of the investigator.
11. Female, greater than or equal to 19 years of age and any race.

Exclusion Criteria:

1. Concurrent therapy with any other non-protocol anti-cancer therapy
2. For Phase I patients only: Current therapy with hormone replacement therapy, or any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators
3. Presence of neuropathy > grade 2 (NCI-CTC version 3.0) at baseline
4. History of any other malignancy requiring active treatment
5. Clinically significant cardiovascular disease (e.g., hypertension [BP > 150/100], myocardial infarction or stroke within 6 months, unstable angina), New York Heart Association (NYHA) Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
6. Currently active infection.
7. History of HIV infection or chronic hepatitis B or C.
8. The presence of any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of the drugs in this protocol or place the subject at undue risk for treatment complications
9. Pregnancy or breast feeding
10. A history of a severe hypersensitivity reaction to nab-paclitaxel.
11. Any reason why, in the opinion of the investigator, the patient should not participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: All patients; All participants enrolled.	Drug: Nanoparticle Albumin Bound Paclitaxel; IV administered over 30 minutes. 100 mg/m2 on days 1 and 8; Other Names: Abraxane; Drug: doxorubicin; 50 mg/m2 every 3 weeks; Other Names: Adriamycin; Drug: cyclophosphamide; 500 mg/m2 given every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pathologic complete response	1 year
Type, incidence, severity, timing, seriousness and relatedness of adverse events and laboratory abnormalities	one year

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall clinical response rate (OcRR)	one year

Collaborators and Investigators

• Sponsor: University of Utah
• Collaborators: Celgene Corporation
• Investigators: Principal Investigator: Hung Khong, MD, University of Utah

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (ACTUAL): March 24, 2017
• Study Completion (ACTUAL): March 24, 2017

Study Registration Dates

• First Submitted: March 17, 2010
• First Submitted That Met QC Criteria: March 18, 2010
• First Posted (ESTIMATE): March 19, 2010

Study Record Updates

• Last Update Posted (ACTUAL): March 31, 2017
• Last Update Submitted That Met QC Criteria: March 29, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Paclitaxel; Albumin-Bound Paclitaxel; Doxorubicin
• Other Study ID Numbers: HCI53989