Clinical Trials /

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

NCT03135171

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Trastuzumab and Pertuzumab in Combination With Tocilizumab in Subjects With Metastatic HER2 Positive Breast Cancer Resistant to Trastuzumab
  • 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

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2017.002
  • SECONDARY ID: HUM00125505
  • NCT ID: NCT03135171

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
TrastuzumabTrastuzumab, Pertuzumab and Tocilizumab
PertuzumabTrastuzumab, Pertuzumab and Tocilizumab
TocilizumabTrastuzumab, Pertuzumab and Tocilizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Trastuzumab, Pertuzumab and TocilizumabExperimental
  • Trastuzumab
  • Pertuzumab
  • Tocilizumab

Eligibility 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; ejection fraction
             decreased to below institutional normal or change 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Phase II Dose of Tocilizumab
Time Frame:10 weeks
Safety Issue:
Description: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

Measure:The Frequency of Adverse Events at Each Dose Level
Time Frame:30 days after last treatment dose
Safety Issue:
Description:The number of grade 3 and 4 adverse events at each dose level will be described.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Michigan Cancer Center

Last Updated

May 24, 2017