Phase II Short-term Adjuvant Therapy and Biomarker Studies With Targeted Agents in Women With Estrogen Receptor Negative Breast Cancer

NCT01471106 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 2010-0794NCI-2012-00037KG09 1020
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical research study is to learn if dasatinib can help prevent breast cancer from developing in the unaffected breast. Dasatinib is designed to decrease the activity of one or more proteins that are responsible for the uncontrolled growth of tumor cells. This is an investigational study. Dasatinib is FDA approved and commercially available for the treatment of leukemia. Its use in breast cancer patients in investigational. Up to 66 patients will take part in this multicenter study. Up to 60 will be enrolled at MD Anderson.

Conditions

Breast Cancer

Keywords

Breast Cancer; Estrogen Receptor Negative Breast Cancer; Biomarker studies; Ki-67; Dasatinib; BMS-354825; Sprycel

Outcome Measures

Primary Outcomes (1)

• Change in Ki-67 in Breast Tissue of High-Risk Women

  Change in Ki-67 measured in baseline and month 3 using contralateral breast Fine Needle Aspiration (FNA) samples. Samples evaluated by immunohistochemistry (IHC). Baseline and follow up Ki-67 values presented in percentage (%) of cell positive, change reflects difference in percentage. Ki-67 is measured as a continuous variable and a one-way ANOVA followed by Dunnett's multiple comparison test comparing the change of Ki-67 of each of the three treated groups with control.

  up to 3 months

Secondary Outcomes (3)

• To Evaluate Dasatinib Induced Modulation of Biomarker in the Serum Including Insulin Like Growth Factor (IGF) Pathway

  up to 3 months

• To Evaluate Dasatinib Induced Modulation of Biomarker in the Serum Including Insulin Like Growth Factor (IGF) Pathway

  up to 3 months

• To Evaluate Dasatinib Induced Modulation of Biomarker in the Serum Including Insulin Like Growth Factor (IGF) Pathway

  up to 3 months

Study Arms (3)

Group 1: Dasatinib 40 mg

EXPERIMENTAL

Dasatinib 40 mg by mouth once a day for 3 months (+/- 7 days), At the end of the 3 months (+/- 7 days) participants undergo a repeat FNA and blood collection for the same marker analyses.

Drug: Dasatinib

Group 3: No Dasatinib

NO INTERVENTION

No treatment control group. At the end of the 3 months (+/- 7 days) participants undergo a repeat FNA and blood collection for the same marker analyses.

Group 2: Dasatinib 80 mg

EXPERIMENTAL

Dasatinib 80 mg by mouth once a day for 3 months (+/- 7 days). At the end of the 3 months (+/- 7 days) participants undergo a repeat FNA and blood collection for the same marker analyses.

Drug: Dasatinib

Interventions

Dasatinib DRUG

Group 1: 40 mg by mouth once a day. Group 2: 80 mg by mouth once a day.

Also known as: BMS-354825, Sprycel

Group 1: Dasatinib 40 mg; Group 2: Dasatinib 80 mg

Eligibility Criteria

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

You may qualify if:

• Histological confirmation of ER negative breast carcinoma (defined as less than 10%), stage I, II, or III
• Completed all adjuvant therapy including (if indicated) endocrine, trastuzumab, radiation therapy
• At least 18 years of age.
• Female: A female is eligible to enter and participate in the study if she is of: a. Non-childbearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation, hysterectomy alone, hysterectomy and bilateral salpingo-oophorectomy, bilateral salpingo-oophorectomy alone or women who are post-menopausal); or b. Childbearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility. This category includes women with oligomenorrhoea (severe), women who are perimenopausal, and young women who have begun to menstruate), has a negative serum pregnancy test at screening, and agrees to one of the following where considered acceptable to the local IRB/IEC: • Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm).
• (Continued from above) • Abstinence from sexual intercourse from 2 weeks prior to administration of the investigational product, throughout the active study treatment period. • Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject. • Any intrauterine device (IUD). • Barrier methods including diaphragm or condom with a spermicide.
• Able to swallow and retain oral medication.
• ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2.
• Provided written informed consent.
• Adequate bone marrow function: Hemoglobin \>/= 9 gm/dL. • Absolute granulocyte count \>/= 1,500/mm\^3 (1.5 x 10\^9/L). • Platelets \>/= 75,000/mm\^3 (100 x 10\^9/L).
• Serum creatinine \< 1.4 mg/dL or calculated creatinine clearance (CrCl) \>/= 30 mL/min
• Total bilirubin \</= 1.5 times the upper limit of the reference range
• Aspartate and alanine transaminase (AST or ALT) \</= 2 times the upper limit of the reference range.
• Patients must have a baseline ECG with QTcF within the normal range within 28 days prior to registration.
• Normal mammogram of unaffected breast within 12 months prior to study entry.

You may not qualify if:

• Unwillingness to undergo RPFNA.
• Contraindication to RPFNA including breast implant(s), bilateral radiation, anticoagulation (excluding those on 81mg aspirin).
• Concurrent medical condition that would increase drug toxicity: Pleural or pericardial effusion, coagulation or platelet function disorder, ongoing or recent (less than 3 months gastrointestinal bleeding)
• Uncontrolled angina, congestive heart failure, MI (within last 6 months), congenital long QT syndrome, history of clinically significant ventricular arrhythmia, prolonged QTcF interval on pre-entry EKG (greater than normal range)
• Hypokalemia or hypomagnesemia if it cannot be corrected
• Is a pregnant or lactating female.
• Has evidence of recurrent or metastatic (Stage IV) breast cancer.
• Is considered medically unfit for the study by the investigator as a result of the medical interview, physical exam, or screening investigations.
• Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to dasatinib
• Has received treatment with any investigational drug in the previous 4 weeks.
• Has received chemotherapy, immunotherapy, biologic therapy or endocrine therapy within the past 12 weeks.
• Is currently receiving oral steroid treatment (inhaled steroids are permitted)
• Oral estrogen, progesterone, testosterone therapy within last 3 months.
• Concomitant Medications: Drugs that are considered category D (Consider therapy modification) and X (Avoid combination) using the Lexicomp database are prohibited. Concomitant drugs that fall into categories A (No known interaction), B (no action needed) and C (monitor therapy) are allowed.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Susan G. Komen Breast Cancer Foundation: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Duke University

Durham, North Carolina, 27708, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Dr. Arun K. Banu
• Organization: M D Anderson Cancer Center

barun@mdanderson.org

(713) 792-2817

Study Officials

• Banu Arun, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2011
• First Posted: November 11, 2011
• Study Start: January 21, 2014
• Primary Completion: January 31, 2024
• Study Completion: May 30, 2024
• Last Updated: July 10, 2024
• Results First Posted: July 10, 2024

Record last verified: 2024-06

Locations

US (2)