Neoadjuvant Treatment of Breast Cancer

NCT00254592 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: UCI 05-382005-4550
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Study Aims

1. 1.To measure the clinic response rates in patients with breast cancer more than 2 cm and/or lymph node positive breast cancer treated with 2-4 cycles of biweekly doxorubicin, cyclophosphamide with Granulocyte-macrophage colony-stimulating factor (GM-CSF) (days 4-13) followed by weekly carboplatin/nab-paclitaxel given for 3 weeks, followed by 1 week of rest, for a total of 9-12 doses. (Her-2 positive patients, in addition, will receive Trastuzumab weekly (12-16 doses) and Her-2 negative patients will receive Bevacizumab (6-8 doses) q 2 weeks).
2. 2.To measure the microscopic pathological response rate of this regimen.
3. 3.To measure toxicity and the delivered dose intensity of this regimen.
4. 4.To assess the association between microscopic pathologic complete response and clinical complete response at the primary tumor site in these patients.
5. 5.To determine whether the GM-CSF increases the post treatment dendritic cells (S100+) percentage in the tumor draining lymph node as compared to pretreatment S100+ cells.
6. 6.To determine whether the patients with a higher percent S100+ have a better clinical, pathological response, Disease Free Survival (DFS), and overall Survival (OS).
7. 7.To determine whether flow cytometry of dendritic cells performed post-treatment in blood sample shows an increase in dendritic cell population compared to pretreatment levels.

Conditions

Breast Cancer

Keywords

Inflammatory; Breast Cancer; Female; Neo-adjuvant; HER-2 positive; Hormone receptor

Outcome Measures

Primary Outcomes (1)

• Overall Clinical Response to the Dose Dense Regimen

  Measure clinical response rates in patients with breast cancer more than 2 cm and/or lymph node positive breast cancer treated with 2- 4 cycles of biweekly doxorubicin, cyclophosphamide with GMCSF (day 4-13) followed by weekly carboplatin/nab-paclitaxel given for 3 weeks, followed by 1 week of rest, for a total of 9-12 doses. (Her-2 positive patients, in addition, will receive Trastuzumab weekly (12-16 doses) and Her-2 negative patients will receive Bevacizumab (6-8 doses) q 2 weeks).

  3 years

Study Arms (1)

AC with GM-CSF and Carboplatin/Nab-Paclitaxel

EXPERIMENTAL

Doxorubicin and cyclophosphamide (AC) administered intravenously every 14 days up to a total of 4 cycles, with GM-CSF on days 4-13, depending on tumor response. Two weeks after the completion of AC, weekly doses of carboplatin/nab-paclitaxel will be given for 3 weeks, followed by 1 week of rest, for a total of 9-12 doses. Subjects who receive 4 cycles of AC will receive 9 doses of nab-paclitaxel and subjects who receive 2 cycles of AC will receive 12 weeks of nab-paclitaxel. In addition, subjects will receive trastuzumab weekly (12-16) doses if they are Her-2 positive and bevacizumab (6-8) doses every 2 weeks if they are Her-2 negative. Each clinic visit will last approximately ½ hour.

Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Carboplatin; Drug: Nab-paclitaxel; Drug: GM-CSF; Drug: Trastuzumab; Drug: Bevacizumab

Interventions

Doxorubicin DRUG

60 mg/m2 IV, bolus once a day every 14 days x 2-4 cycles

Also known as: Adriamycin, NSC-123127

AC with GM-CSF and Carboplatin/Nab-Paclitaxel

Cyclophosphamide DRUG

600 mg/m2 IV once a day every 14 days x 2-4 cycles

Also known as: Cytoxan, NSC-26271

AC with GM-CSF and Carboplatin/Nab-Paclitaxel

Carboplatin DRUG

AUC 2 IV weekly for 9-12 doses beginning two weeks after completion of last AC dose

Also known as: Paraplatin, NSC 241240

AC with GM-CSF and Carboplatin/Nab-Paclitaxel

Nab-paclitaxel DRUG

100 mg/m2 IV over 30 min weekly for 9-12 doses beginning two weeks after completion of last AC dose

Also known as: Albumin-stabilized nanoparticle formulation of paclitaxel, Abraxane, ABI 007

AC with GM-CSF and Carboplatin/Nab-Paclitaxel

GM-CSF DRUG

250 μg/mL IV or on day 4-13 of each subcutaneous cycle of doxorubicin and injection cyclophosphamide

Also known as: Sargramostim, Leukine, Berlex, NSC-613795

AC with GM-CSF and Carboplatin/Nab-Paclitaxel

Trastuzumab DRUG

4mg/kg, and then2 mg/kg q wk IV weekly for 12-16 doses beginning two weeks after completion of last AC dose

AC with GM-CSF and Carboplatin/Nab-Paclitaxel

Bevacizumab DRUG

10mg/kg q 2 wks

Also known as: Avastin

AC with GM-CSF and Carboplatin/Nab-Paclitaxel

Eligibility Criteria

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

You may qualify if:

• Patients must be women with a histologically confirmed diagnosis of breast cancer that is more than 2 cm and/or lymph node positive. Histologic confirmation shall be by either core needle biopsy or incisional biopsy. Punch biopsy is allowed if invasive breast cancer is documented.
• Patients must meet one of the criteria defined below (indicate one):
• Selected Stage IIB (T3, N0, M0) or IIIA (T3, N1-2, M0) disease judged primarily unresectable by an experienced breast surgeon; or otherwise deemed - appropriate candidates for neoadjuvant treatment.
• Stage IIIB (T4, Any N, M0) or (Any T, N3, M0) disease.
• Physical examination, chest x-ray and any x-rays or scans needed for tumor assessment must be performed within 90 days prior to registration.
• All patients must have a multiple gated acquisition (MUGA) scan or echocardiogram scan performed within 90 days prior to registration and left ventricular ejection fraction (LVEF) percentage must be greater than the institutional lower limit of normal.
• Patients must have a serum creatinine and bilirubin ≤ the institutional upper limit of normal, and an serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) ≤ 2x the institutional upper limit of normal. These tests must have been performed within 90 days prior to registration.
• Patients must have an absolute neutrophil count (ANC) of ≥ 1,500/μl and a platelet count of ≥ 100,000/μl. These tests must have been performed within 90 days prior to registration.
• Patients must have a performance status of 0-2 by Zubrod criteria
• In calculating days of tests and measurements, the day a test or measurement is done is considered Day 0. Therefore, if a test is done on a Monday, the Monday four weeks later would be considered Day 28. This allows for efficient patient scheduling without exceeding the guidelines. If Day 28 or 42 falls on a weekend or holiday, the limit may be extended to the next working day.
• All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

You may not qualify if:

• Patients with the clinical diagnosis of congestive heart failure or angina pectoris are NOT eligible.
• Pregnant or nursing women may not participate due to the possibility of fetal harm or of harm to nursing infants from this treatment regimen. Women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. A urine pregnancy test is required for women of childbearing potential.

Sponsors & Collaborators

• University of California, Irvine: lead

Study Sites (1)

Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; Cyclophosphamide; Carboplatin; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim; Trastuzumab; Bevacizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Coordination Complexes; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Rita S. MEHTA, MD
• Organization: University of California Irvine Medical Center

rsmehta@uci.edu

(714) 456-5153

Study Officials

• Rita Mehta, M.D.

  Chao Family Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: November 15, 2005
• First Posted: November 16, 2005
• Study Start: October 1, 2005
• Primary Completion: September 4, 2013
• Study Completion: September 4, 2013
• Last Updated: February 28, 2019
• Results First Posted: November 11, 2013

Record last verified: 2019-02

Locations

US (1)