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Trastuzumab and Pertuzumab in Combination With Tocilizumab in Subjects With Metastatic HER2 Positive Breast Cancer Resistant to Trastuzumab

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ClinicalTrials.gov Identifier: NCT03135171
Recruitment Status : Recruiting
First Posted : May 1, 2017
Last Update Posted : February 8, 2019
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

Brief Summary:
The goal in this Phase 1 dose-escalation trial of the anti-IL-6R monoclonal antibody tocilizumab in combination with trastuzumab and pertuzumab in subjects with metastatic HER2 positive breast cancer is to determine the safety, tolerability and recommended Phase 2 dose of tocilizumab given with trastuzumab and pertuzumab every 3 weeks.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Trastuzumab Drug: Pertuzumab Drug: Tocilizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Multi-Center Trial of Trastuzumab and Pertuzumab in Combination With Tocilizumab in Subjects With Metastatic HER2 Positive Breast Cancer Resistant to Trastuzumab
Actual Study Start Date : May 22, 2017
Estimated Primary Completion Date : April 1, 2019
Estimated Study Completion Date : August 1, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Trastuzumab, Pertuzumab and Tocilizumab Drug: Trastuzumab
All dose levels will receive 8 mg/kg loading dose for cycle 1, followed by 6 mg/kg in subsequent cycles, every 3 weeks.

Drug: Pertuzumab
Dose Levels two and three will receive 840 mg loading dose for cycle 1, followed by 420 mg in subsequent cycles, every 3 weeks.

Drug: Tocilizumab
Tocilizumab 4-8 mg/kg, administered intravenously every three weeks




Primary Outcome Measures :
  1. Recommended Phase II Dose of Tocilizumab [ Time Frame: 10 weeks ]
    The primary objective is to determine the highest dose level of tocilizumab (up to 8 mg/kg every 3 weeks) that, when given in combination with trastuzumab and pertuzumab every three weeks in subjects with HER2 positive metastatic breast cancer, will result in less than 25% incidence of DLT. DLTs (Dose Limiting Toxicity) will be assessed within the first two cycles (up to 10 weeks) and defined as any toxicity of grade 3 or 4, unless specifically described in the protocol.


Secondary Outcome Measures :
  1. The Frequency of Adverse Events at Each Dose Level [ Time Frame: 30 days after last treatment dose ]
    The number of grade 3 and 4 adverse events at each dose level will be described.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women or men with histologically confirmed breast cancer that overexpresses HER2 (defined by ASCO-CAP 2013 guidelines performed using FDA-approved tests by laboratories with demonstrated proficiency) that is metastatic or unresectable
  • Subjects must have received trastuzumab in the metastatic setting and experienced disease progression on this drug.
  • Any number of prior therapies is permitted. Prior therapy with other HER2 targeted agents (TDM-1, pertuzumab, lapatinib) is allowed.
  • The last dose of chemotherapy must have occurred ≥3 weeks prior to study registration.
  • The last radiation therapy must have occurred ≥3 weeks prior to study registration.
  • Age≥ 18 years
  • Eastern Cooperative Oncology Group Performance Status of 0 or 1 (An attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death.)
  • Measurable and/or non-measureable disease by RECIST criteria must be present.
  • Adequate organ and bone marrow function
  • Subjects with treated brain metastases are eligible provided the metastases are clinically stable and greater than 8 weeks has elapsed from time of treatment and date of initiation of study drug.
  • Males and females of reproductive potential must use two forms of effective contraception during the duration of the trial and for minimum of 7 months after last dose of tocilizumab, trastuzumab, or pertuzumab.

Exclusion Criteria:

  • Intolerance to previous trastuzumab or pertuzumab therapy
  • Previous treatment with tocilizumab or other cytokine-targeted biologic disease modifying antirheumatic drugs (including adalimumab, certolizumab, etanercept, golimumab, infliximab, anakinra) within 3 months of enrollment
  • Participation in other investigational studies concurrently if these therapies include a therapeutic intervention
  • Treatment with any investigational agent within 30 days (or 5 serum half-lives of the investigational drug, whichever is longer) of enrollment
  • Concurrent second malignancy or history of HER2 negative breast cancer within five years
  • Comorbidity or intercurrent illness
  • Major surgery within 8 weeks or planned major surgery during study and up to 6 months after discontinuation of study drug
  • Left ventricular systolic dysfunction, defined as ejection fraction below institutional normal by echocardiography or MUGA (multigated acquisition scan); current or past clinical diagnosis of congestive heart failure; history of ejection fraction decreased to below institutional normal or desease of greater than 15% attributable to past trastuzumab or pertuzumab therapy
  • Evidence of current serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease.
  • History of diverticulitis, diverticulosis requiring antibiotic treatment or chronic ulcerative lower GI (gastrointestinal) disease such as Crohn's disease, ulcerative colitis or other symptomatic lower GI conditions that might predispose to perforations
  • Infections as detailed in the protocol
  • Immunization with a live/attenuated vaccine within 30 days of enrollment
  • Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation
  • Pre-existing CNS (Central Nervous System) demyelination or seizure disorders
  • Any medical or psychological condition that in the opinion of the principal investigator would interfere with safe completion of the trial
  • Pregnancy or breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03135171


Contacts
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Contact: Monika Burness, M.D. 1-800-865-1125 mburness@umich.edu

Locations
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United States, Illinois
University of Chicago Not yet recruiting
Chicago, Illinois, United States, 60637
Contact: Rita Nanda, MD         
United States, Michigan
University of Michigan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Monika Burness, M.D.    800-865-1125    mburness@umich.edu   
Principal Investigator: Monika Burness, M.D.         
United States, New York
Yale University Not yet recruiting
New Haven, New York, United States, 06520
Contact: Lajos Pusztai, MD, DPhil         
Sponsors and Collaborators
University of Michigan Rogel Cancer Center
Investigators
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Principal Investigator: Monika Burness, M.D. University of Michigan Rogel Cancer Center

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Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT03135171     History of Changes
Other Study ID Numbers: UMCC 2017.002
HUM00125505 ( Other Identifier: University of Michigan Comprehensive Cancer Center )
First Posted: May 1, 2017    Key Record Dates
Last Update Posted: February 8, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Pertuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents