Metformin Hydrochloride in Treating Women With Stage I or Stage II Breast Cancer That Can Be Removed By Surgery

NCT00984490 | Terminated Results DMC

• 3 other identifiers: VICC BRE 0942P30CA068485VU-VICC-BRE-0942
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: Metformin hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying how well metformin hydrochloride works in treating women with stage I or stage II breast cancer that can be removed by surgery.

Conditions

Breast Cancer

Keywords

stage I breast cancer; stage II breast cancer

Outcome Measures

Primary Outcomes (1)

• Change in Ki67 Levels Before and After Treatment

  Change in Ki67 levels in pre-treatment, pre-surgery and post-treatment, surgically excised breast tissue. Measured by percentage of positive-staining nuclei with a minimum of 0% to a maximum of 100%. A mean score is determined.

  baseline and between 8-23 days

Secondary Outcomes (1)

• Changes in Circulating Insulin-like Growth Factor 1 (IGF-1) and IGF Binding Protein 3 (IGFBP-3)

  baseline and 23 days

Study Arms (1)

Metformin

EXPERIMENTAL

Metformin: 850 mg orally (PO) twice daily (BID) for 7-21 days, discontinued 24-36 hrs prior to surgery

Drug: metformin hydrochloride; Other: laboratory biomarker analysis

Interventions

metformin hydrochloride DRUG

Metformin: 850 mg orally (PO) twice daily (BID) for 7-21 days, discontinued 24-36 hrs prior to surgery

Metformin

laboratory biomarker analysis OTHER

Blood and tissue collection to determine the in situ biologic effect of metformin

Metformin

Eligibility Criteria

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

You may qualify if:

• Patients must provide informed written consent
• Eastern Cooperative Oncology Group performance status 0-1.
• Clinical stage I, II or IIIA invasive mammary carcinoma, any estrogen receptors(ER), progesterone receptors (PR), or Human Epidermal Growth Factor Receptor (HER2/NEU) status
• Patients who have measurable residual tumor at the primary site Measurable disease: a mass that can be reproducibly measured by physical examination and/or ultrasound and is at least 1 cm in size by physical examination or ultra-sound measurement
• Patients who will undergo surgical treatment with either segmental resection or total mastectomy with lymph node evaluation
• Consultations: All patients should be evaluated by a surgeon prior to study entry.
• Available core biopsies from the time of diagnosis. These may include sections paraffin-embedded material.
• Female subjects ≥18 years of age
• No prior chemotherapy for this primary breast cancer.
• Patients with a prior history of contralateral breast cancer are eligible if they have no evidence of recurrence of their initial primary breast cancer.
• Women may have been taking tamoxifen or raloxifene as a preventive agent prior to study entry but must have discontinued the drug for at least 21 days prior to study enrollment.
• Patients must have adequate hepatic and renal function. All tests must be obtained less than 4 weeks from study entry. This includes:
• Creatinine \</= to 1.5X upper limits of normal
• Bilirubin, SGOT, SGPT \< or = to 1.5X upper limits of normal
• Able to swallow and retain oral medication

You may not qualify if:

• Patients with locally advanced disease who are candidates and wish to undergo preoperative chemotherapy at the time of initial evaluation. Patients with operable locally advanced disease (stage IIIA) are eligible for participation.
• Locally recurrent breast cancer
• Evidence of distant metastatic disease (i.e. lung, liver, bone, brain, etc.)
• History of diabetes mellitus
• Pregnant or lactating women
• Metformin treatment within 30 days of study entry
• Serious medical illness that in the judgment of the treating physician places the patient at high risk of operative mortality.
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded.
• History of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinomas are eligible
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
• History of a medical condition leading to chronic hypoxemia and/or ischemia (congestive heart failure, emphysema or chronic lung disease requiring supplemental oxygen)
• Chronic metabolic acidosis (serum HCO3- \< or = to 20 or requiring sodium bicarbonate supplementation)
• Concurrent anti-cancer therapy (chemotherapy, radiotherapy, immunotherapy, hormonal therapy, or any other biologic therapy)
• Concurrent treatment with an investigational agent
• Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study drug.

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Vanderbilt-Ingram Cancer Center - Cool Springs

Nashville, Tennessee, 37064, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

Because this study was closed prematurely, no assay level markers or pathways were performed consequently no data are available to provide results.

Results Point of Contact

• Title: Ingrid Mayer, MD
• Organization: Vanderbilt-Ingram Cancer Center

ingrid.mayer@vanderbilt.edu

615-936-2033

Study Officials

• Ingrid Mayer, M.D.

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: September 24, 2009
• First Posted: September 25, 2009
• Study Start: September 1, 2009
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2011
• Last Updated: February 1, 2024
• Results First Posted: July 13, 2012

Record last verified: 2024-01

Locations

US (3)