Chemotherapy with or without Metformin Hydrochloride in Treating Patients with HER2 Positive Breast Cancer That Can Be Removed by Surgery

Status: Temporarily Closed to Accrual

Description

This randomized phase II trial studies how well chemotherapy with or without metformin hydrochloride work in treating patients with HER2 positive breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as docetaxel, carboplatin, trastuzumab, pertuzumab, and pegfilgrastim, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Metformin hydrochloride may prevent or lower risk of breast cancer and decrease cancer cells, lower risk of cancer spreading. It is not yet known whether giving metformin hydrochloride with chemotherapy will work better in treating patients with breast cancer.

Eligibility Criteria

Inclusion Criteria

  • Written informed consent obtained from study participant or study participant’s legal representative and ability for study participant to comply with the requirements of the study
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
  • Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by needle core biopsy; fine-needle aspiration is not sufficient; incisional/excisional biopsy is not allowed; in case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint
  • Study participants must be cT1c - cT4a-d any N, M0; any T is allowed if node positive (biopsy proven and HER2 positive) including no primary invasive cancer or only ductal breast carcinoma in situ (DCIS); metastatic workup is not required
  • Breast tumor must be >= 1.5 cm in maximum diameter by clinical or any radiologic measurement, if node negative; if node is positive by biopsy, study participant will be eligible regardless of the size of the breast primary; in case of inflammatory breast cancer, the extent of inflammation/erythema can be used as measurable lesion
  • Multifocal or multicentric breast cancer is allowed if all the lesions are biopsied and are HER2 positive; largest lesion will be assigned the target lesion
  • Must be HER2-positive in primary breast tumor or lymph node by the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines 2013
  • Ejection fraction (EF) >= 50% by multigated acquisition (MUGA) or echocardiography (ECHO) within 4 weeks prior to first dose of study treatment
  • No prior cancer chemotherapy allowed
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcl
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 X institutional upper limit of normal
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Alkaline phosphatase (ALK Phos) =< 2.5 X institutional upper limit of normal
  • Creatinine clearance >= 50 mL/min
  • Women of child-bearing potential must agree to use adequate contraception (double barrier method of birth control or abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
  • Negative pregnancy test (either urine or serum) within 14 days prior to randomization for all women of childbearing potential (above)

Exclusion Criteria

  • Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
  • Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the study participant or the quality of the study data
  • Current or anticipated use of other investigational agents
  • Prior chemotherapy for any malignancy
  • Prior radiation therapy for breast cancer
  • Previous malignant disease being disease-free for less than 5 years (except carcinoma in situ [CIS] of the cervix and non-melanoma skin cancer)
  • Patients with diabetes on metformin; patients with diabetes and not on metformin will be eligible if it is deemed safe after consultation with the patient physician managing diabetes
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin or other agents used in study
  • 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

Locations & Contacts

Kansas

Kansas City
University of Kansas Cancer Center
Status: Temporarily closed to accrual
Contact: Qamar Jamal Khan
Phone: 913-588-6029
Email: QKHAN@kumc.edu
University of Kansas Cancer Center-West
Status: Temporarily closed to accrual
Contact: Qamar Jamal Khan
Phone: 913-588-6029
Email: QKHAN@kumc.edu
Overland Park
University of Kansas Cancer Center-Overland Park
Status: Temporarily closed to accrual
Contact: Qamar Jamal Khan
Phone: 913-588-6029
Email: QKHAN@kumc.edu

Missouri

Kansas City
The University of Kansas Cancer Center-North
Status: Temporarily closed to accrual
Contact: Qamar Jamal Khan
Phone: 913-588-4085
Email: QKHAN@kumc.edu
The University of Kansas Cancer Center-South
Status: Temporarily closed to accrual
Contact: Qamar Jamal Khan
Phone: 913-588-6029
Email: QKHAN@kumc.edu
Lee's Summit
The University of Kansas Cancer Center-Lee's Summit
Status: Temporarily closed to accrual
Contact: Qamar Jamal Khan
Phone: 913-588-6029
Email: QKHAN@kumc.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To study the efficacy of metformin hydrochloride (metformin) as a repurposed agent in HER2 positive breast cancer when added to standard neo-adjuvant chemotherapy.

SECONDARY OBJECTIVES:

I. To study the tolerability of metformin combined with anti-HER2 neo-adjuvant chemotherapy.

TERTIARY OBJECTIVES:

I. To study the effect of addition of metformin to chemotherapy on biomarkers of HER2 resistance and insulin resistance (blood and tissue).

OUTLINE: Patients are randomized to 1 or 2 arms.

ARM I: Patients receive docetaxel intravenously (IV) over 60 minutes, carboplatin IV over 30 minutes, trastuzumab IV over 30-60 minutes, and pertuzumab IV over 30-60 minutes on day 1. Patients may also receive pegfilgrastim subcutaneously (SC) on day 2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo surgery.

ARM II: Patients receive chemotherapy as in Arm I. Patients also receive metformin hydrochloride orally (PO) once daily (QD) on days 1-21 of course 1 and twice daily (BID) on days 1-21 of subsequent courses. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo surgery.

After completion of study treatment, patients are followed up at 2-6 weeks.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Kansas Cancer Center

Principal Investigator
Qamar Jamal Khan

Trial IDs

Primary ID IIT-2016-HERMET
Secondary IDs NCI-2017-02470
Clinicaltrials.gov ID NCT03238495