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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2014 by H. Lee Moffitt Cancer Center and Research Institute
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT02139358
First received: May 13, 2014
Last updated: June 20, 2014
Last verified: June 2014
  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.


Condition Intervention Phase
Breast Cancer
Drug: Gemcitabine
Drug: Trastuzumab
Drug: Pertuzumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Phase I: Recommended Phase II Dose [ Time Frame: Upon Determination of Phase II Dose - Approximately 6 Months ] [ Designated as safety issue: Yes ]
    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.

  • Phase II: Objective Response Rate (ORR) [ Time Frame: Up to 36 Months ] [ Designated as safety issue: No ]
    Objective Response Rate: Complete Response (CR) + Partial Response (PR) using Response Evaluation in Solid Tumors (RECIST) 1.1 criteria for the combination of gemcitabine+trastuzumab+pertuzumab at the recommended phase II dose. Any patient who receives any dose of the study treatment will be evaluated for the safety/toxicity endpoints in the trial. To be considered evaluable for the primary efficacy endpoint (ORR) the patient must undergo two treatment cycles followed by a response scan. CR: Disappearance of all evidence of tumor for at least two cycles of therapy. Tumor markers must be normal. PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking a reference the baseline sum longest diameter.


Secondary Outcome Measures:
  • Phase II: Progression Free Survival (PFS) [ Time Frame: Up to 36 Months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 46
Study Start Date: September 2014
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I Dose Escalation / Phase II Treatment
Single arm, non-randomized, open label phase I/II multisite Simon two stage minimax trial. Gemcitabine plus trastuzumab and pertuzumab.
Drug: Gemcitabine
The phase I trial will start at the recommended phase II dose (RP2D) for gemcitabine but will have a de-escalation dose levels in the event that an unacceptable toxicity requires dose reduction. Dose level 0 = gemcitabine (1200mg/m2) IV D1,8 q21 days; Dose level -1 = gemcitabine (1000mg/m2) IV D1,8 q21 days; Dose level -2 = gemcitabine (850mg/m2) IV D1,8 q21 days. The RP2D will be the dose level where 0-1 dose limiting toxicities (DLTs) in six patients occur.
Other Name: GEMZAR®
Drug: Trastuzumab
Trastuzumab will be given using an 8mg/kg loading dose on cycle one, day one (C1D1), followed by 6mg/kg IV on subsequent cycles every (q) 21 days.
Other Name: Herceptin®
Drug: Pertuzumab
Pertuzumab will be given using an 840mg IV loading dose on C1D1, followed by 420mg IV on subsequent cycles q21 days.
Other Name: PERJETA®

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02139358

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Not yet recruiting
Tampa, Florida, United States, 33612
Contact: Dawn Carney    813-745-1807    dawn.carney@moffitt.org   
Principal Investigator: Hatem Soliman, M.D.         
Sub-Investigator: Hyo Han, M.D.         
Sub-Investigator: Roohi Ismail-Khan, M.D.         
Sub-Investigator: Loretta Loftus, M.D.         
Sub-Investigator: Susan Minton, D.O.         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Genentech
Investigators
Principal Investigator: Hatem Soliman, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT02139358     History of Changes
Other Study ID Numbers: MCC-17656, ML28939
Study First Received: May 13, 2014
Last Updated: June 20, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Breast - Female
Metastatic
HER2+

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Gemcitabine
Trastuzumab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on July 23, 2014