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Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer

NCT02139358

Description:

The purpose of this study is to evaluate the safety and activity of gemcitabine plus trastuzumab and pertuzumab in patients with metastatic human epidermal growth factor receptor 2 (HER2)+ breast cancer who have progressed on at least one prior line of chemotherapy plus HER2 targeted agent such as T-DM1, trastuzumab, or lapatinib.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer
  • Official Title: Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: MCC-17656
  • SECONDARY ID: ML28939
  • NCT ID: NCT02139358

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
GemcitabineGEMZAR®Dose Escalation / Phase II Treatment
TrastuzumabHerceptin®Dose Escalation / Phase II Treatment
PertuzumabPERJETA®Dose Escalation / Phase II Treatment

Purpose

The purpose of this study is to evaluate the safety and activity of gemcitabine plus trastuzumab and pertuzumab in patients with metastatic human epidermal growth factor receptor 2 (HER2)+ breast cancer who have progressed on at least one prior line of chemotherapy plus HER2 targeted agent such as T-DM1, trastuzumab, or lapatinib.

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation / Phase II TreatmentExperimentalSingle arm, non-randomized, open label phase I/II multisite Simon two stage minimax trial. Gemcitabine plus trastuzumab and pertuzumab.
  • Gemcitabine
  • Trastuzumab
  • Pertuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Adult males or females (aged 18 or older) with histologically confirmed, metastatic
             human epidermal growth factor receptor 2 (HER2)+ (by immunohistochemistry (IHC) 3+ or
             fluorescence in situ hydridization (FISH) ratio ≥ 2.0) breast cancer

          -  Have progressed on at least one prior line of chemotherapy plus HER2 directed therapy
             such as trastuzumab and/or pertuzumab in the metastatic setting. T-DM1 would count as
             a line of therapy and patients previously treated with T-DM1 are eligible.

          -  Have not been treated with gemcitabine in the metastatic setting

          -  Measurable disease per Response Evaluation in Solid Tumors (RECIST) 1.1 criteria

          -  Eastern Cooperative Oncology Group (ECOG) performance status 2≤

          -  Left Ventricular Ejection Fraction (LVEF) ≥ 50% at baseline as determined by either
             echocardiogram (ECHO) or multiple gated acquisition scan (MUGA)

          -  Adequate bone marrow function as indicated by the following: absolute neutrophil count
             (ANC) >1500/µL; Platelets ≥100,000/µL; Hemoglobin >10 g/dL

          -  Adequate renal function, as indicated by creatinine ≤1.5x upper limit of normal (ULN)

          -  Adequate liver function, as indicated by bilirubin ≤1.5x ULN, aspartic transaminase
             (AST) or alanine transaminase (ALT) <2x ULN unless related to metastatic breast cancer
             to the liver (in which case AST/ALT < 5x ULN is allowed).

          -  Signed informed consent

          -  Adequate birth control in sexually active women of childbearing potential

        Exclusion Criteria:

          -  Active uncontrolled infection or major concurrent illness which in the opinion of the
             investigator would render the participant unsafe to proceed with the study

          -  Uncontrolled central nervous system (CNS) metastases. Treated, non-progressing CNS
             disease (documented by brain magnetic resonance imaging [MRI]) off corticosteroids for
             at least 1 month potential participants are eligible.

          -  Women who are pregnant or lactating

          -  Prior chemotherapy within the last 3 weeks (last 6 weeks for nitrosureas/mitomycin)

          -  Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator
             lesion (unless objective disease recurrence or progression within the radiation portal
             has been documented since completion of radiation)

          -  Other concomitant active malignancies

          -  History of significant cardiac disease, cardiac risk factors or uncontrolled
             arrhythmias

          -  Ejection fraction <50% or below the lower limit of the institutional normal range,
             whichever is lower

          -  Hypersensitivity to any of the study medications

          -  Untreated psychiatric conditions preventing informed consent
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I: Recommended Phase II Dose
Time Frame:Upon Determination of Phase II Dose - Approximately 6 Months
Safety Issue:
Description:Establishing the recommended phase II dose for the combination of gemcitabine+trastuzumab+pertuzumab with safety data described using Common Terminology Criteria for Adverse Events (CTCAE) 4.0 terminology. Any patient who receives any dose of the study treatment will be evaluated for the safety/toxicity endpoints in the trial.

Secondary Outcome Measures

Measure:Phase II: Progression Free Survival (PFS)
Time Frame:Up to 36 Months
Safety Issue:
Description:Median progression free survival (in months) for all patients evaluable for response. The time-to-event data will be summarized using Kaplan-Meir curve method for all patients who are evaluable for the ORR endpoint. Progressive disease (PD): At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the beginning of treatment or the appearance of one or more new lesions.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • Breast - Female
  • Metastatic
  • HER2+

Last Updated

November 30, 2017