Low Dose Chemotherapy With Aspirin in Patients With Breast Cancer After Neoadjuvant Chemotherapy

NCT01612247 | Unknown DMC

• 1 other identifier: V1010
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 3

Brief Summary

Patients with stage II-III breast cancer who do not achieve a pathologic complete response to neoadjuvant chemotherapy at the time of surgery will be treated with oral low dose continuous cyclophosphamide and methotrexate (CM) in combination with aspirin following surgery and radiotherapy. The primary endpoint is to assess toxicity and safety with secondary endpoints of cytokine correlates and relapse free survival (RFS) at 2 years. The investigators design tests the null hypothesis (H0) that the true primary toxicity event rate will be 5% or less, against an alternative hypothesis (HA) event rate of 25% or more.

Conditions

Breast Cancer

Keywords

Breast Cancer; Neoadjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Toxicity and Safety

  The primary endpoint of the study is toxicity and safety. Serious adverse events, grade 3 and 4 nonhematologic toxicity, and hematologic toxicity requiring removal of the patient from study treatment will be reviewed. A fixed sample size design to test for primary toxicity events will be conducted. Sample size was selected based upon a null hypothesis that the toxicity rate will be 5% or less and that the alternative hypothesis toxicity rate will be 25% or more.

  18 months

Secondary Outcomes (1)

• Biomarker Analysis

  18 months

Interventions

Cyclophosphamide and Methotrexate and Aspirin DRUG

Cyclophosphamide 50 mg PO daily x 28 days, cycles 1-4 Methotrexate 2.5 mg PO twice daily, days 1 and 2 each week x 4 weeks, cycles 1-4 ASA: 325 mg PO daily x 28 days, cycles 3 and 4 Treatment will be given for a total of 4 cycles.

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed,clinical stage II-III invasive breast cancer prior to neoadjuvant therapy (CTEP Simplified Disease Classification 10021980 or 10006190).
• Patients may be male or female, premenopausal or postmenopausal. Tumor may be ER/PR positive or negative. Margins must be negative, with the following exception: microscopic positive anterior margin adjacent to skin is allowed.
• Patients must receive chemotherapy prior to definitive surgery. Any preoperative chemotherapy regimen is acceptable, with the exception of anti-angiogenic agents.
• Patients must have residual invasive breast cancer in breast and/or axillary lymph nodes by pathology at the time of surgery (not pathologic CR). All of the following clinical responses are acceptable: partial response (PR), stable disease (SD), progressive disease (PD).
• Patients may receive hormonal therapy concurrently with study therapy. Hormonal therapy, if given, should start 4 weeks prior to initiation of study treatment in order to avoid a confounding effect on the correlative studies.
• Age \>18 years. Because breast cancer is extremely rare in this age group, children are excluded from this study.
• Median life expectancy of greater than 2 years.
• ECOG performance status \<1 (Karnofsky \>60%; see Appendix A).
• Patients must have normal organ and marrow function as defined below:
• absolute neutrophil count \>1.5 K/cmm
• platelets \>100 K/cmm
• total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) \<2.5 X institutional upper limit of normal
• creatinine within normal institutional limits OR
• creatinine clearance \>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal

You may not qualify if:

• Patients may not have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study and must have recovered from adverse events due to agents administered more than 4 weeks earlier.
• Patients may not be receiving any other antineoplastic or investigational agents concurrently with study treatment with the exception of hormonal therapy.
• Patients with HER-2 positive breast cancer are excluded.
• History of allergic reactions attributed to aspirin or other agents used in the study.
• Patients may not begin study treatment during radiotherapy, but may begin immediately after completing radiotherapy treatment.
• Patients may not have received prior bevacizumab, or other anti-angiogenic agents (e.g., sorafenib, pazopanib, AZD2171, PTK787, VEGF Trap, etc.).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with hypertension that cannot be controlled by medications (\>160/100 mmHg despite optimal medical therapy) are not eligiblePatients with poorly controlled hypertension (systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 90 mmHg or higher) are ineligible.
• Patients on chronic aspirin therapy, anti-platelet agents, anti-coagulation agents or nonsteroidal anti-inflammatory drugs (NSAIDs) at any dose are excluded. Patients who take these drugs intermittently must be willing to abstain for the duration of the study treatment.
• Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain oral medication are excluded.
• Patients with any of the following conditions are excluded:
• Prior history of gastrointestinal or central nervous system bleeding, or documented or self-reported blood in stools or bright red blood per rectum
• Recent (within 12 months) history of clinically significant bleeding
• Serious or non-healing wound, ulcer, or bone fracture.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment.

Sponsors & Collaborators

• University of Vermont: lead
• Maimonides Medical Center: collaborator
• Dartmouth-Hitchcock Medical Center: collaborator

Study Sites (3)

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

NOT YET RECRUITING

Maimonides Cancer Center

Brooklyn, New York, 11220, United States

RECRUITING

University of Vermont

Burlington, Vermont, 05401, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide; Methotrexate; Aspirin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 30, 2012
• First Posted: June 5, 2012
• Study Start: February 1, 2011
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2014
• Last Updated: June 5, 2012

Record last verified: 2012-05

Locations

US (3)