Breast CancerPhase 1NCT03135171
Trastuzumab and Pertuzumab in Combination With Tocilizumab in Subjects With Metastatic HER2 Positive Breast Cancer Resistant to Trastuzumab
A Phase 1 study testing Trastuzumab, Pertuzumab and Tocilizumab in people with Breast Cancer, run by University of Michigan Rogel Cancer Center at 3 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Trastuzumab, Pertuzumab and Tocilizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 3 sitesUnited States
- Study dates
- 26 Jul 2017to 20 Mar 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
University of Chicago
Chicago, Illinois, 60637
Yale University
New Haven, New York, 06520
About this study
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
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.
- Conditions
- Breast Cancer
- Being tested
- Trastuzumab, Pertuzumab, Tocilizumab
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrastuzumabDrug
All dose levels will receive 8 mg/kg loading dose for cycle 1, followed by 6 mg/kg in subsequent cycles, every 3 weeks.
PertuzumabDrug
Dose Levels two and three will receive 840 mg loading dose for cycle 1, followed by 420 mg in subsequent cycles, every 3 weeks.
TocilizumabDrug
Tocilizumab 4-8 mg/kg, administered intravenously every three weeks
| Study group | Role | What they receive |
|---|---|---|
| Trastuzumab, Pertuzumab and Tocilizumab | Experimental | Not described Receives: Drug: Trastuzumab; Drug: Pertuzumab; Drug: Tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended Phase II Dose of Tocilizumab
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.
Measured: 10 weeks
Secondary outcomes (1)
The Frequency of Adverse Events at Each Dose Level
The number of grade 3 and 4 adverse events at each dose level will be described.
Measured: 30 days after last treatment dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2017
- Study start26 Jul 2017
- Primary completion16 Mar 2020
- Study completion20 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Monika Burness, M.D., Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03135171
- Sponsor's protocol ID
- UMCC 2017.002
- Other IDs
- HUM00125505
- Status last verified
- Sep 2021
- First submitted
- 25 Apr 2017
- Last updated
- 10 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03135171
- Acronym / sponsor ID
- UMCC 2017.002
- Conditions
- Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- 26 Jul 2017 (actual)
- Primary completion
- 16 Mar 2020 (actual)
- Study completion
- 20 Mar 2020 (actual)
- First posted
- 1 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Trastuzumab, Pertuzumab and Tocilizumab | Experimental | Drug: Trastuzumab, Drug: Pertuzumab, Drug: Tocilizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrastuzumabAll dose levels will receive 8 mg/kg loading dose for cycle 1, followed by 6 mg/kg in subsequent cycles, every 3 weeks. | Drug | Trastuzumab, Pertuzumab and Tocilizumab |
| PertuzumabDose Levels two and three will receive 840 mg loading dose for cycle 1, followed by 420 mg in subsequent cycles, every 3 weeks. | Drug | Trastuzumab, Pertuzumab and Tocilizumab |
| TocilizumabTocilizumab 4-8 mg/kg, administered intravenously every three weeks | Drug | Trastuzumab, Pertuzumab and Tocilizumab |
Primary outcome
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.
1 secondary outcome
The Frequency of Adverse Events at Each Dose Level
Time frame: 30 days after last treatment dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Monika Burness, M.D. principal investigator
University of Michigan Rogel Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Trastuzumab, Pertuzumab and Tocilizumab in people with Breast Cancer, run by University of Michigan Rogel Cancer Center at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recommended Phase II Dose of Tocilizumab (time frame: 10 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2021.