Back to resultsGemcitabine, Trastuzumab, and Pertuzumab in the Treatment of Metastatic HER2-Positive Breast Cancer After Prior Trastuzumab/Pertuzumab, or Pertuzumab Based Therapy
Primary Purpose
Metastatic HER2-Positive Breast Cancer
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Gemcitabine
Trastuzumab
Pertuzumab
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic HER2-Positive Breast Cancer focused on measuring Gemcitabine,, Trastuzumab, Pertuzumab, 14-124
Eligibility Criteria
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
Sites / Locations
- Hartford Healthcare Cancer Institute @ Hartford Hospital
- Memorial Sloan Kettering at Basking Ridge
- Memorial Sloan Kettering Monmouth
- Memorial Sloan Kettering Westchester
- Memorial Sloan Kettering Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Gemcitabine, Trastuzumab, and Pertuzuma
Arm Description
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.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
progression-free survival
Progression-free survival (PFS) is defined from time from treatment assignment to disease progression or death, whichever comes first.
response
Response to treatment will be determined using both RECIST and PRC ( PET Response Criteria criteria).
overall survival
Progression-free survival and median overall survival will also be estimated by the Kaplan-Meier method.
safety
This study will use the NCI Common Toxicity Criteria (CTC) AE version 4.0 for toxicity.
Full Information
NCT ID
NCT02252887
First Posted
September 26, 2014
Last Updated
October 2, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Genentech, Inc., Hoffmann-La Roche, Hartford HealthCare
1. Study Identification
Unique Protocol Identification Number
NCT02252887
Brief Title
Gemcitabine, Trastuzumab, and Pertuzumab in the Treatment of Metastatic HER2-Positive Breast Cancer After Prior Trastuzumab/Pertuzumab, or Pertuzumab Based Therapy
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 12, 2015 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Genentech, Inc., Hoffmann-La Roche, Hartford HealthCare
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic HER2-Positive Breast Cancer
Keywords
Gemcitabine,, Trastuzumab, Pertuzumab, 14-124
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Gemcitabine, Trastuzumab, and Pertuzuma
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Intervention Type
Drug
Intervention Name(s)
Pertuzumab
Primary Outcome Measure Information:
Title
progression free
Description
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).
Time Frame
3 months
Secondary Outcome Measure Information:
Title
progression-free survival
Description
Progression-free survival (PFS) is defined from time from treatment assignment to disease progression or death, whichever comes first.
Time Frame
2 years
Title
response
Description
Response to treatment will be determined using both RECIST and PRC ( PET Response Criteria criteria).
Time Frame
2 years
Title
overall survival
Description
Progression-free survival and median overall survival will also be estimated by the Kaplan-Meier method.
Time Frame
2 years
Title
safety
Description
This study will use the NCI Common Toxicity Criteria (CTC) AE version 4.0 for toxicity.
Time Frame
2 years
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chau Dang, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hartford Healthcare Cancer Institute @ Hartford Hospital
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06102
Country
United States
Facility Name
Memorial Sloan Kettering at Basking Ridge
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Facility Name
Memorial Sloan Kettering Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Facility Name
Memorial Sloan Kettering Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
31774522
Citation
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.
Results Reference
derived
Links:
URL
http://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center
Learn more about this trial
Gemcitabine, Trastuzumab, and Pertuzumab in the Treatment of Metastatic HER2-Positive Breast Cancer After Prior Trastuzumab/Pertuzumab, or Pertuzumab Based Therapy
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