Randomized Trial of Neo-adjuvant Chemotherapy With or Without Metformin for HER2 Positive Operable Breast Cancer

NCT03238495 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00140673
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 6

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.

Conditions

HER2-positive Breast Cancer

Keywords

Operable breast cancer; Neo-adjuvant chemotherapy

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response (pCR)

  pCR at surgery

  Up to 6 weeks after last chemotherapy treatment

Study Arms (2)

Chemotherapy Only

ACTIVE COMPARATOR

Taxotere, Carboplatin, Herceptin + Pertuzumab (TCH+P)

Drug: Taxotere, Carboplatin, Herceptin + Pertuzumab

Chemotherapy plus Metformin

EXPERIMENTAL

TCH+P plus metformin

Drug: Taxotere, Carboplatin, Herceptin + Pertuzumab; Drug: Metformin

Interventions

Taxotere, Carboplatin, Herceptin + Pertuzumab DRUG

TCH+P chemotherapy every 3 weeks for 6 cycles: Taxotere 75mg/m2, Carboplatin AUC 6, Herceptin 6mg/kg (first cycle loading dose of 8mg/kg), Pertuzumab 420mg (first cycle loading does of 840mg)

Chemotherapy Only; Chemotherapy plus Metformin

Metformin DRUG

TCH+P chemotherapy every 3 weeks for 6 cycles. Metformin 850 mg daily during the first cycle, then 850 mg twice daily for the remaining 5 cycles.

Chemotherapy plus Metformin

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Qamar Khan: lead

Study Sites (6)

The University of Kansas Cancer Center, West Clinic

Kansas City, Kansas, 66112, United States

RECRUITING

The University of Kansas Cancer Center, Westwood Campus

Kansas City, Kansas, 66205, United States

RECRUITING

The University of Kansas Cancer Center, Overland Park Clinic

Overland Park, Kansas, 66210, United States

RECRUITING

The University of Kansas Cancer Center, South Clinic

Kansas City, Missouri, 64131, United States

RECRUITING

The University of Kansas Cancer Center, North Clinic

Kansas City, Missouri, 64154, United States

RECRUITING

The University of Kansas Cancer Center, Lee's Summit Clinic

Lee's Summit, Missouri, 64064, United States

RECRUITING

MeSH Terms

Interventions

Docetaxel; Carboplatin; Trastuzumab; pertuzumab; Metformin

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biguanides; Guanidines; Amidines

Study Officials

• Qamar Khan, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Nurse Navigator

CONTACT

913-945-7552; ctnursenav@kumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 31, 2017
• First Posted: August 3, 2017
• Study Start: August 15, 2017
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2023
• Last Updated: December 7, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)