Clinical trial NCT03238495: Randomized Trial of Neo-adjuvant Chemotherapy With or Without Metformin for HER2 Positive Operable Breast Cancer
Official title: Randomized Trial of Neo-adjuvant Chemotherapy With or Without Metformin for HER2 Positive Operable Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: HER2-positive Breast Cancer
Keywords: Operable breast cancer
Neo-adjuvant chemotherapy
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
First posted: 2017-08-03
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to determine the efficacy of metformin as a repurposed agent in human epidermal growth factor receptor 2 (HER2) positive breast cancer when added to standard neo-adjuvant chemotherapy.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group Performance Status (ECOG 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 node (N), no metastases (M0). Any tumor (T) is allowed if node positive (biopsy proven and HER2 positive) including no primary invasive cancer or only ductal 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 ASCO/CAP guidelines 2013: http://www.asco.org/guidelines/her2
* Ejection fraction (EF) greater than 50% by MUGA or ECHO within 4 weeks prior to first dose of study treatment.
* No prior cancer chemotherapy allowed.
* Adequate organ and marrow function as defined below, unless deemed non-clinically significant and approved by the Principal Investigator:

  * Absolute neutrophil count ≥ 1,500/mcL
  * Platelets ≥ 100,000/mcl
  * total bilirubin within normal institutional limits
  * AST(SGOT) ≤ 2.5 X institutional upper limit of normal
  * ALT(SPGT) ≤ 2.5 X institutional upper limit of normal
  * ALK Phos ≤ 2.5 X institutional upper limit of normal
  * Creatinine clearance \> 50mL/min
* Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.
* Negative pregnancy test within 14 days prior to randomization

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.

Primary outcomes:
measure: Pathologic complete response (pCR)
timeFrame: Up to 6 weeks after last chemotherapy treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: The University of Kansas Cancer Center, West Clinic
state: Kansas
city: Kansas City
country: United States
facility: The University of Kansas Cancer Center, Westwood Campus
state: Kansas
city: Overland Park
country: United States
facility: The University of Kansas Cancer Center, Overland Park Clinic
state: Kansas
city: Kansas City
country: United States
facility: The University of Kansas Cancer Center, South Clinic
state: Missouri
city: Kansas City
country: United States
facility: The University of Kansas Cancer Center, North Clinic
state: Missouri
city: Lee's Summit
country: United States
facility: The University of Kansas Cancer Center, Lee's Summit Clinic
state: Missouri
Study officials:
affiliation: University of Kansas Medical Center
name: Qamar Khan, MD
role: PRINCIPAL_INVESTIGATOR
References: