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Metastatic Breast CancerPhase 1NCT00932373

A Study of Trastuzumab-MCC-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer Who Have Previously Received a Trastuzumab-Containing Regimen

A Phase 1 study testing trastuzumab-MCC-DM1 in people with Metastatic Breast Cancer, run by Genentech, Inc..

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a phase I, multicenter, open-label, dose-escalation study of single-agent trastuzumab-MCC-DM1 administered by intravenous (IV) infusion in patients with HER2-positive metastatic breast cancer (MBC) who have previously received trastuzumab. Read more about this study

Who is it for?
Any age
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
trastuzumab-MCC-DM1
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
No sites listed yet
Study dates
Apr 2006to Jun 2009
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Histologically documented, incurable, locally advanced or metastatic breast cancer
  • Evaluable or measurable HER2-positive disease
  • History of progression during or within 60 days after treatment with any prior trastuzumab-containing chemotherapy regimen for HER2-positive breast cancer
  • Previous treatment with chemotherapy for MBC
  • Granulocyte count ≥ 1,500/μL, platelet count ≥ 100,000/μL, and hemoglobin ≥ 9 g/dL
  • Serum bilirubin ≤ 1.5 mg/dL; AST, ALT, and alkaline phosphatase ≤ 2.5 × upper limit of normal (ULN) except for: Patients with hepatic metastases: ALT and AST ≤ 5 × ULN Patients with hepatic and/or bone metastases: alkaline phosphatase ≤ 5 × ULN
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  • Serum creatinine ≤ 1.5 mg/dL or creatinine clearance of ≥ 60 mL/min based on a 24-hour urine collection
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
  • Women of childbearing potential and men must agree to use an effective method of birth control (e.g., hormonal, barrier) while receiving study treatment

Who cannot join

  • History of significant cardiac disease, unstable angina, CHF, myocardial infarction, or ventricular arrhythmia requiring medication
  • History of Grade ≥ 3 hypersensitivity reaction to trastuzumab
  • History of any toxicity to trastuzumab that resulted in trastuzumab being permanently discontinued
  • Symptomatic brain metastases or any radiation or surgery for brain metastases within 3 months of first study treatment
  • Require supplemental oxygen for daily activities
  • Grade ≥ 2 peripheral neuropathy
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  • Bisphosphonate therapy for symptomatic hypercalcemia
  • Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy for the treatment of breast cancer within 4 weeks of first study treatment
  • Any experimental therapy within 4 weeks of first study treatment
  • Any major surgical procedure within 4 weeks of first study treatment
  • History of clinically symptomatic liver disease, including viral or other hepatitis, current or history of alcoholism, or cirrhosis
  • Pregnancy or lactation
  • Cardiac troponin I ≥ 0.2 ng/mL
  • Ejection fraction < 50% or below the lower limit of normal determined by echocardiogram or MUGA scan
  • Prior cumulative doxorubicin dose of > 360 mg/m2 or equivalent

About this study

Official title: A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of Trastuzumab-MCC-DM1 (PRO132365) Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer Who Have Previously Received a Trastuzumab-Containing Regimen

This is a phase I, multicenter, open-label, dose-escalation study of single-agent trastuzumab-MCC-DM1 administered by intravenous (IV) infusion in patients with HER2-positive metastatic breast cancer (MBC) who have previously received trastuzumab. The study will assess the safety, tolerability, and pharmacokinetics of trastuzumab-MCC-DM1 and determine the dose and schedule to be used in Phase II.

Being tested
trastuzumab-MCC-DM1
Keywords
HER2-positive breast cancer, MBC, Trastuzumab emtansine, Herceptin, T-DM1
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • trastuzumab-MCC-DM1Drug

    Intravenous escalating dose

Study groups in NCT00932373
Study groupRoleWhat they receive
1ExperimentalNot described
Receives: Drug: trastuzumab-MCC-DM1

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment

    The time frame for AEs is study treatment initiation until 30 days after last administration of study treatment or at the time of initiation of another anti-cancer therapy, which ever occurs first.

    The time frame for SAEs is study treatment initiation until 90 days after last administration of study treatment or at the time of initiation of another anti-cancer therapy, which ever occurs first.

    Measured: Study treatment initiation until 30 or 90 days after last administration of study treatment

  2. Number of Patients With Dose Limiting Toxicities (DLTs)

    DLT is defined as one of the following as per investigator related to study drug:

    • Grade ≥ 3 non-hematologic, non-hepatic major organ toxicity
    • Grade ≥ 3 cardiac toxicity, including cardiac troponin I elevation or any new segmental wall abnormality as determined by non-invasive cardiac imaging
    • Grade ≥ 4 thrombocytopenia
    • Grade ≥ 4 neutropenia (absolute neutrophil count < 500/μ L) lasting > 4 days or accompanied by fever
    • Grade ≥ 4 anemia
    • Grade ≥ 3 serum bilirubin, hepatic transaminase (alanine aminotransferase or aspartate aminotransferase), or alkaline phosphatase For patients with Grade 2 hepatic transaminase or alkaline phosphatase levels at baseline as a result of liver metastases or bone metastases, a hepatic transaminase or alkaline phosphatase level ≥ 10 times the upper limit of normal will be considered a DLT.
    • Weekly cohorts only: Toxicity preventing retreatment on Cycle 1, Day 8 or toxicity preventing re-treatment on Cycle 1, Days 15 and Day 22

    Measured: A minimum of 21 days after first dose of trastuzumab-MCC-DM1

  3. Maximum Tolerated Dose (MTD)

    The highest dose level resulting in a DLT in ≤ 1 of 6 patients was declared the MTD.

    Measured: A minimum of 21 days after first dose of trastuzumab-MCC-DM1

  4. Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations

    Measured: 3-Week and Weekly Cohorts: Cycle 1 Day 1 Pre-dose 30 minutes and 4 hours after the end of infusion; Cycle 1 Day 2, 3, 4, 8 (Pre-dose 30 minutes after the end of infusion) 11, 15 (Pre-dose 30 minutes after the end of infusion) and 18

  5. PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations

    Measured: 3-Week and Weekly Cohorts: Cycle 1 Day 1 Pre-dose 30 minutes and 4 hours after the end of infusion; Cycle 1 Day 2, 3, 4, 8 (Pre-dose 30 minutes after the end of infusion) 11, 15 (Pre-dose 30 minutes after the end of infusion) and 18

  6. PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations

    Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.

    Measured: 3-Week and Weekly Cohorts: Cycle 1 Day 1 Pre-dose 30 minutes and 4 hours after the end of infusion; Cycle 1 Day 2, 3, 4, 8 (Pre-dose 30 minutes after the end of infusion) 11, 15 (Pre-dose 30 minutes after the end of infusion) and 18

Secondary outcomes (4)

  1. Percentage of Participants With an Objective Response

    The occurrence of an objective response was determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST). An objective response was defined as a complete response or a partial response as determined on 2 consecutive occasions ≥ 4 weeks apart. A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter of target lesions.

    Measured: Baseline to the end of the study (up to 3 years 2 months)

  2. Duration of Objective Response

    Duration of objective response was defined as the time from the initial response to disease progression or death from any cause within 30 days of the last dose of trastuzumab emtansine.

    Measured: Baseline to the end of the study (up to 3 years 2 months)

  3. Progression-free Survival

    Progression-free survival was defined as the time from first dose of trastuzumab emtansine to documented disease progression or death from any cause within 30 days of the last dose of trastuzumab emtansine, whichever occurred earlier. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter of target lesions recorded since treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

    Measured: Baseline to the end of the study (up to 3 years 2 months)

  4. Percentage of Participants With Anti-therapeutic Antibodies to Trastuzumab Emtansine

    After the start of trastuzumab emtansine treatment, serum samples were collected every 3 weeks prior to trastuzumab emtansine dosing for detection of anti-therapeutic antibodies using a validated assay. A bridging antibody electrochemiluminescence assay (ECLA) was used to detect antibodies to trastuzumab emtansine. The assay utilized trastuzumab emtansine conjugated to biotin and a ruthenium label to form a complex with anti-trastuzumab emtansine antibodies. The antibody complex was captured by streptavidin-coated paramagnetic beads.

    Measured: Baseline to the end of the study (up to 3 years 2 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jul 2009 (estimated)
  2. Study startApr 2006
  3. Primary completionJun 2009
  4. Study completionJun 2009

Resources

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00932373
Sponsor's protocol ID
TDM3569g
Status last verified
Aug 2015
First submitted
30 Jun 2009
Last updated
26 Aug 2015

Publications

  • Beeram M, Krop IE, Burris HA, Girish SR, Yu W, Lu MW, Holden SN, Modi S. A phase 1 study of weekly dosing of trastuzumab emtansine (T-DM1) in patients with advanced human epidermal growth factor 2-positive breast cancer. Cancer. 2012 Dec 1;118(23):5733-40. doi: 10.1002/cncr.27622. Epub 2012 May 30.

    PubMed 22648179

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing trastuzumab-MCC-DM1 in people with Metastatic Breast Cancer, run by Genentech, Inc..

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 9 inclusion and 15 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 26 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.

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?

Yes. Results are posted in the registry (first posted 30 Jul 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment (time frame: Study treatment initiation until 30 or 90 days after last administration of study treatment). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00932373, which also lists 1 linked publication.

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 26 Aug 2015.

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