Gemcitabine, Trastuzumab, and Pertuzumab in the Treatment of Metastatic HER2-Positive Breast Cancer After Prior Trastuzumab/Pertuzumab, or Pertuzumab Based Therapy

Phase II Study of Gemcitabine, Trastuzumab, and Pertuzumab in the Treatment of Metastatic HER2-Positive Breast Cancer After Prior Trastuzumab/Pertuzumab- or Pertuzumab-Based Therapy

The purpose of this study is to see if a combination of drugs can help to treat breast cancer. This is a Phase II study which will test whether this combination of drugs is effective and will provide further information on side effects and safety. A standard chemotherapy, gemcitabine, will be combined with 2 other drugs that target the HER2 receptor. The HER2 receptor is a growth protein on the surface of some breast cancer cells that provides messages telling the breast cancer cell to grow. The standard chemotherapy will be gemcitabine.. The other two drugs work against HER2. One is called trastuzumab (Herceptin) and it is commonly given to women with advanced and early HER2 positive breast cancer. The other drug, pertuzumab (Perjeta), is also given to women with advanced HER2 positive breast cancer. The drugs in this study are each individually approved for the treatment of metastatic breast cancer. However, this study is looking at the effectiveness of gemcitabine with trastuzumab and pertuzumab when given to women who have advanced HER2 positive breast cancer who have had prior trastuzumab + pertuzumab or pertuzumab-based therapy.

Study Overview

• Status: Completed
• Conditions: Metastatic HER2-Positive Breast Cancer
• Intervention / Treatment: Drug: Gemcitabine; Drug: Pertuzumab; Drug: Trastuzumab

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Healthcare Cancer Institute @ Hartford Hospital
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering at Basking Ridge
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth
  • New York
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ to 18
• Stage IV HER2 (+) breast cancer
• Histologically documented HER2 (+) breast cancer as defined as IHC 3+ or FISH amplification of ≥ 2.0 of primary or metastatic site; results from the local lab are acceptable.
• lECOG performance status 0 -1
• Prior treatment with trastuzumab + pertuzumab (HP)-based therapy or pertuzumab-based in the neoadjuvantadjuvant, unresectable, locally advanced, or metastatic setting.
• ≤ 3 prior chemotherapies in the metastatic setting. Prior anthracycline, taxane, gemcitabine, and anti-HER2 agents (i.e. trastuzumab, pertuzumab, lapatinib, neratinib, TDM-1, etc.) are allowed. If patients received prior gemcitabine, it could not have been combined with pertuzumab. Patients should have progression of disease on current therapy.
• Measurable or non-measurable disease.
• LVEF ≥ 50%
• Hematologic parameters: white blood cell (WBC) count of ≥ 3000/ul, absolute neutrophil count (ANC) ≥ 1000/ul, platelets ≥ 100,000/ul, hemoglobin ≥10.0 g/dl
• Non-hematologic parameters: bilirubin ≤ 1.5 mg/dl, AST/ALT≤ 2.5 x upper limit of normal (ULN), alkaline phosphatase ≤ 5 x ULN.
• Creatinine ≤ 1.5 mg/dl
• Patients with "treated and stable" brain lesions of a duration of ≥ 2 months may be enrolled.

Exclusion Criteria:

• History of prior unstable angina, myocardial infarction, CHF, uncontrolled ventricular arrhythmias within 12 months
• History of prior ≥ G 3 hypersensitivity (HSR) or any toxicity to trastuzumab or pertuzumab that warranted permanent cessation of this agent
• History of hepatitis B or C
• Pregnant patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Gemcitabine, Trastuzumab, and Pertuzuma; The regimen will consist of gemcitabine at 1000mg/m^2 IV weekly days 1 + 8 q 3 weeks + trastuzumab every 3 weeks (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks) + pertuzumab every 3 weeks (840 mg as a loading dose followed by 420 mg every 3 weeks), all given intravenously (IV). Trastuzumab may be given IV weekly (4 mg/kg loading dose followed by 2 mg/kg weekly) in lieu of the every 3 week schedule. A loading dose of trastuzumab will not be required for patients who have received it < 6 weeks prior to Cycle 1 Day 1.

Drug: Gemcitabine; Drug: Pertuzumab; Drug: Trastuzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression free	Progression-free survival (PFS) is defined from time from treatment assignment to disease progression or death, whichever comes first. The primary endpoint is PFS and secondary endpoint will include the response rate using the RECIST criteria (version 1.1).	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival	Progression-free survival (PFS) is defined from time from treatment assignment to disease progression or death, whichever comes first.	2 years
response	Response to treatment will be determined using both RECIST and PRC ( PET Response Criteria criteria).	2 years
overall survival	Progression-free survival and median overall survival will also be estimated by the Kaplan-Meier method.	2 years
safety	This study will use the NCI Common Toxicity Criteria (CTC) AE version 4.0 for toxicity.	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Hoffmann-La Roche; Genentech, Inc.; Hartford HealthCare
• Investigators: Principal Investigator: Chau Dang, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• Iyengar NM, Smyth LM, Lake D, Gucalp A, Singh JC, Traina TA, DeFusco P, Fornier MN, Goldfarb S, Jhaveri K, Modi S, Troso-Sandoval T, Patil S, Ulaner GA, Jochelson M, Norton L, Hudis CA, Dang CT. Efficacy and Safety of Gemcitabine With Trastuzumab and Pertuzumab After Prior Pertuzumab-Based Therapy Among Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: A Phase 2 Clinical Trial. JAMA Netw Open. 2019 Nov 1;2(11):e1916211. doi: 10.1001/jamanetworkopen.2019.16211.

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2015
• Primary Completion (Actual): July 24, 2025
• Study Completion (Actual): July 24, 2025

Study Registration Dates

• First Submitted: September 26, 2014
• First Submitted That Met QC Criteria: September 26, 2014
• First Posted (Estimated): September 30, 2014

Study Record Updates

• Last Update Posted (Actual): July 25, 2025
• Last Update Submitted That Met QC Criteria: July 24, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Trastuzumab; Pertuzumab; Gemcitabine,; 14-124
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Trastuzumab; Gemcitabine; Pertuzumab
• Other Study ID Numbers: 14-124