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CompletedNCT00932373Updated Aug 26, 2015Results posted

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 interventional study of trastuzumab-MCC-DM1 in Metastatic Breast Cancer, sponsored by Genentech, Inc.. Completed. Per ClinicalTrials.gov, last updated 2015-08-26.

Sponsored by Genentech, Inc. · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
54
Allocation
Non-randomized
Sex
All
01

Study 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. 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.

02

Conditions studied

  • Metastatic Breast Cancer

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Keywords

  • HER2-positive breast cancer
  • MBC
  • Trastuzumab emtansine
  • Herceptin
  • T-DM1
03

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 54 is below the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

Genentech, Inc. is the lead sponsor of 507 studies on the registry; 23 are open to participants now.

Of its 90 completed or terminated interventional studies of FDA-regulated products, 50 (56%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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
  • 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

Exclusion criteria

Exclusion Criteria:

  • 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
  • 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
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
54 participants (actual)

Study arms

  • Experimental
    1

    Drug: trastuzumab-MCC-DM1

Interventions

  • Drugtrastuzumab-MCC-DM1

    Intravenous escalating dose

06

What researchers measure

Primary outcomes

  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.

    Time frame: 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

    Time frame: 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.

    Time frame: 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

    Time frame: 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

    Time frame: 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.

    Time frame: 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

  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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

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

07

Results

Posted Jul 30, 2015

Participant flow

Approximately four centers in the United States were to participate in the study to enroll approximately 50-60 patients. Between 25 April 2006 and 20 May 2008, 54 patients were enrolled and 52 were treated.

Participant flow — Overall Study
MilestoneTrastuzumab-MCC-DM1 0.3 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 0.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 2.4 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 3.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 4.8 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg WeeklyTrastuzumab-MCC-DM1 1.6 mg/kg WeeklyTrastuzumab-MCC-DM1 2.0 mg/kg WeeklyTrastuzumab-MCC-DM1 2.4 mg/kg WeeklyTrastuzumab-MCC-DM1 2.9 mg/kg Weekly
Started3111153333163
Completed00011020130
Not completed3110143132133
Withdrew: Progressive disease310010102192
Withdrew: Adverse event00002101021
Withdrew: Physician decision00102000010
Withdrew: Dose limiting toxicity00000100000
Withdrew: Withdrawal by subject00000000100
Withdrew: Clinical progression00000010000
Withdrew: Lack of efficacy00000000010

Outcome measures

PrimaryPercentage 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.

Time frame:
Study treatment initiation until 30 or 90 days after last administration of study treatment
Reported as:
Number · percentage of participants
Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment
percentage of participantsTrastuzumab-MCC-DM1 0.3 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 0.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 2.4 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 3.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 4.8 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg WeeklyTrastuzumab-MCC-DM1 1.6 mg/kg WeeklyTrastuzumab-MCC-DM1 2.0 mg/kg WeeklyTrastuzumab-MCC-DM1 2.4 mg/kg WeeklyTrastuzumab-MCC-DM1 2.9 mg/kg Weekly
At least 1 AE100100100100100100100100100100100
AEs with Grade >=333.31000046.710033.366.766.781.333.3
At least 1 SAE33.3100002066.733.333.333.3500
AEs related to treatment66.710010010093.310010066.710087.5100
SecondaryPercentage 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.

Time frame:
Baseline to the end of the study (up to 3 years 2 months)
Reported as:
Number · percentage of participants
Percentage of Participants With an Objective Response
percentage of participantsTrastuzumab-MCC-DM1 0.3 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 0.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 2.4 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 3.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 4.8 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg WeeklyTrastuzumab-MCC-DM1 1.6 mg/kg WeeklyTrastuzumab-MCC-DM1 2.0 mg/kg WeeklyTrastuzumab-MCC-DM1 2.4 mg/kg WeeklyTrastuzumab-MCC-DM1 2.9 mg/kg Weekly
Percentage of Participants With an Objective Response00010026.7010066.766.737.50
SecondaryDuration 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.

Time frame:
Baseline to the end of the study (up to 3 years 2 months)
Reported as:
Median · Months
Duration of Objective Response
MonthsTrastuzumab-MCC-DM1 2.4 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 3.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg WeeklyTrastuzumab-MCC-DM1 1.6 mg/kg WeeklyTrastuzumab-MCC-DM1 2.0 mg/kg WeeklyTrastuzumab-MCC-DM1 2.4 mg/kg Weekly
Duration of Objective ResponseNA (NA to NA)10.5 (4.2 to 10.5)NA (NA to NA)2.9 (NA to NA)NA (NA to NA)5.6 (4.5 to NA)
SecondaryProgression-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.

Time frame:
Baseline to the end of the study (up to 3 years 2 months)
Reported as:
Median · Months
Progression-free Survival
MonthsTrastuzumab-MCC-DM1 0.3 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 0.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 2.4 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 3.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 4.8 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg WeeklyTrastuzumab-MCC-DM1 1.6 mg/kg WeeklyTrastuzumab-MCC-DM1 2.0 mg/kg WeeklyTrastuzumab-MCC-DM1 2.4 mg/kg WeeklyTrastuzumab-MCC-DM1 2.9 mg/kg Weekly
Progression-free Survival2.7 (1.3 to 4.2)1.7 (NA to NA)NA (NA to NA)NA (NA to NA)10.4 (3.4 to 17.1)NA (0.7 to NA)NA (20.8 to NA)4.5 (1.6 to NA)NA (7.2 to NA)5.7 (1.3 to 10.9)2.0 (1.3 to 2.8)
SecondaryPercentage 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.

Time frame:
Baseline to the end of the study (up to 3 years 2 months)
Reported as:
Number · percentage of participants
Percentage of Participants With Anti-therapeutic Antibodies to Trastuzumab Emtansine
percentage of participantsTrastuzumab-MCC-DM1 Every 3 WeeksTrastuzumab-MCC-DM1 Every Weeks
Pre-dose (Cycle 1, Day 1)0.03.7
Any Visit after Dosing4.30.0
PrimaryNumber 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

Time frame:
A minimum of 21 days after first dose of trastuzumab-MCC-DM1
Reported as:
Number · participants
Number of Patients With Dose Limiting Toxicities (DLTs)
participantsTrastuzumab-MCC-DM1 0.3 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 0.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 2.4 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 3.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 4.8 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg WeeklyTrastuzumab-MCC-DM1 1.6 mg/kg WeeklyTrastuzumab-MCC-DM1 2.0 mg/kg WeeklyTrastuzumab-MCC-DM1 2.4 mg/kg WeeklyTrastuzumab-MCC-DM1 2.9 mg/kg Weekly
Number of Patients With Dose Limiting Toxicities (DLTs)00000200012
PrimaryMaximum Tolerated Dose (MTD)

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

Time frame:
A minimum of 21 days after first dose of trastuzumab-MCC-DM1
Reported as:
Number · mg/kg
Maximum Tolerated Dose (MTD)
mg/kgTrastuzumab-MCC-DM1 Every 3 WeeksTrastuzumab-MCC-DM1 Every Weeks
Maximum Tolerated Dose (MTD)3.62.4
PrimaryPharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations
Time frame:
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
Reported as:
Mean · μg/mL
Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations
μg/mLTrastuzumab-MCC-DM1 0.3 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 0.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 2.4 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 3.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 4.8 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg WeeklyTrastuzumab-MCC-DM1 1.6 mg/kg WeeklyTrastuzumab-MCC-DM1 2.0 mg/kg WeeklyTrastuzumab-MCC-DM1 2.4 mg/kg WeeklyTrastuzumab-MCC-DM1 2.9 mg/kg Weekly
Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations9.63 ± 1.7313.3 ± 020.3 ± 076.3 ± 076.2 ± 19.1130 ± 7.7729.6 ± 5.6634.3 ± 4.8148.0 ± 9.5654.8 ± 12.678.1 ± 33.9
PrimaryPK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations
Time frame:
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
Reported as:
Mean · day • μg/mL
PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations
day • μg/mLTrastuzumab-MCC-DM1 0.3 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 0.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 2.4 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 3.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 4.8 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg WeeklyTrastuzumab-MCC-DM1 1.6 mg/kg WeeklyTrastuzumab-MCC-DM1 2.0 mg/kg WeeklyTrastuzumab-MCC-DM1 2.4 mg/kg WeeklyTrastuzumab-MCC-DM1 2.9 mg/kg Weekly
PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations14.5 ± 3.3924.5 ± 042.9 ± 0330 ± 0300 ± 65.8673 ± 12.276.2 ± 10.4130 ± 39.7175 ± 41.0199 ± 54.5212 ± 39.0
PrimaryPK 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.

Time frame:
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
Reported as:
Mean · day
PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations
dayTrastuzumab-MCC-DM1 0.3 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 0.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 2.4 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 3.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 4.8 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg WeeklyTrastuzumab-MCC-DM1 1.6 mg/kg WeeklyTrastuzumab-MCC-DM1 2.0 mg/kg WeeklyTrastuzumab-MCC-DM1 2.4 mg/kg WeeklyTrastuzumab-MCC-DM1 2.9 mg/kg Weekly
PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations1.3 ± 0.21.3 ± 01.3 ± 02.2 ± 03.1 ± 0.74.1 ± 0.72.3 ± 0.63.4 ± 0.83.1 ± 0.33.3 ± 1.12.9 ± 0.5

Adverse events

Collected over Baseline to the end of the study (up to 3 years 2 months). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Trastuzumab-MCC-DM 0.3 mg/kg Every 3 Weeks—1/3 (33.3%)3/3 (100%)
Trastuzumab-MCC-DM 0.6 mg/kg Every 3 Weeks—1/1 (100%)1/1 (100%)
Trastuzumab-MCC-DM 1.2 mg/kg Every 3 Weeks—0/1 (0%)1/1 (100%)
Trastuzumab-MCC-DM 2.4 mg/kg Every 3 Weeks—0/1 (0%)1/1 (100%)
Trastuzumab-MCC-DM 3.6 mg/kg Every 3 Weeks—3/15 (20%)15/15 (100%)
Trastuzumab-MCC-DM 4.8 mg/kg Every 3 Weeks—2/3 (66.7%)3/3 (100%)
Trastuzumab-MCC-DM 1.2 mg/kg Weekly—1/3 (33.3%)3/3 (100%)
Trastuzumab-MCC-DM 1.6 mg/kg Weekly—1/3 (33.3%)3/3 (100%)
Trastuzumab-MCC-DM 2.0 mg/kg Weekly—1/3 (33.3%)3/3 (100%)
Trastuzumab-MCC-DM 2.4 mg/kg Weekly—8/16 (50%)15/16 (93.8%)
Trastuzumab-MCC-DM 2.9 mg/kg Weekly—0/3 (0%)3/3 (100%)
Most frequent serious events
Showing 10 of 17
Most frequent serious events
EventTrastuzumab-MCC-DM 0.3 mg/kg Every 3 WeeksTrastuzumab-MCC-DM 0.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM 1.2 mg/kg Every 3 WeeksTrastuzumab-MCC-DM 2.4 mg/kg Every 3 WeeksTrastuzumab-MCC-DM 3.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM 4.8 mg/kg Every 3 WeeksTrastuzumab-MCC-DM 1.2 mg/kg WeeklyTrastuzumab-MCC-DM 1.6 mg/kg WeeklyTrastuzumab-MCC-DM 2.0 mg/kg WeeklyTrastuzumab-MCC-DM 2.4 mg/kg WeeklyTrastuzumab-MCC-DM 2.9 mg/kg Weekly
Pleural EffusionRespiratory, thoracic and mediastinal disorders0/31/10/10/10/150/30/30/30/30/160/3
PneumoniaInfections and infestations0/30/10/10/10/150/30/31/30/32/160/3
ConvulsionNervous system disorders0/30/10/10/11/151/30/30/30/30/160/3
DysarthriaNervous system disorders0/30/10/10/10/151/30/30/30/30/160/3
Confusional StatePsychiatric disorders0/30/10/10/10/150/31/30/30/30/160/3
DyspnoeaRespiratory, thoracic and mediastinal disorders1/30/10/10/10/150/30/30/30/31/160/3
PneumonitisRespiratory, thoracic and mediastinal disorders0/30/10/10/10/150/30/30/31/30/160/3
CellulitisInfections and infestations0/30/10/10/11/150/30/30/30/31/160/3
Humerus FractureInjury, poisoning and procedural complications0/30/10/10/11/150/30/30/30/30/160/3
Brain OedemaNervous system disorders0/30/10/10/11/150/30/30/30/30/160/3
Most frequent other events
Showing 10 of 81
Most frequent other events
EventTrastuzumab-MCC-DM 0.3 mg/kg Every 3 WeeksTrastuzumab-MCC-DM 0.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM 1.2 mg/kg Every 3 WeeksTrastuzumab-MCC-DM 2.4 mg/kg Every 3 WeeksTrastuzumab-MCC-DM 3.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM 4.8 mg/kg Every 3 WeeksTrastuzumab-MCC-DM 1.2 mg/kg WeeklyTrastuzumab-MCC-DM 1.6 mg/kg WeeklyTrastuzumab-MCC-DM 2.0 mg/kg WeeklyTrastuzumab-MCC-DM 2.4 mg/kg WeeklyTrastuzumab-MCC-DM 2.9 mg/kg Weekly
NEPHROLITHIASISRenal and urinary disorders0/31/10/10/10/150/30/30/30/30/160/3
NASOPHARYNGITISInfections and infestations0/30/10/11/13/150/32/30/31/32/160/3
MUCOSAL INFLAMMATIONGeneral disorders0/30/10/11/11/150/31/30/30/30/160/3
PATHOLOGICAL FRACTUREMusculoskeletal and connective tissue disorders0/30/11/10/10/150/30/30/30/30/160/3
NEUTROPENIABlood and lymphatic system disorders0/30/10/11/10/150/31/30/30/31/160/3
HYPOCALCAEMIAMetabolism and nutrition disorders0/30/10/11/10/150/31/30/30/30/160/3
OEDEMA PERIPHERALGeneral disorders1/30/11/10/11/151/30/30/30/30/160/3
DIARRHOEAGastrointestinal disorders1/30/10/11/12/150/33/31/32/36/161/3
NAUSEAGastrointestinal disorders2/31/10/11/16/151/33/31/31/37/162/3
PLEURAL EFFUSIONRespiratory, thoracic and mediastinal disorders0/31/10/10/10/150/30/30/30/30/160/3

Baseline characteristics

All summaries were based on data from the safety population (patients who received at least one dose of Trastuzumab-MCC-DM1). All summaries were presented for all patients and by dose level and schedule.

Age, Continuous
Age, Continuous(Years)Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 0.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 2.4 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 3.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 4.8 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg WeeklyTrastuzumab-MCC-DM1 1.6 mg/kg WeeklyTrastuzumab-MCC-DM1 2.0 mg/kg WeeklyTrastuzumab-MCC-DM1 2.4 mg/kg WeeklyTrastuzumab-MCC-DM1 2.9 mg/kg WeeklyTotal
Mean60.7 ± 10.147.0 ± 061.0 ± 058.0 ± 052.1 ± 10.348.0 ± 6.055.3 ± 10.053.0 ± 6.155.3 ± 3.250.9 ± 14.058.3 ± 11.052.9 ± 10.7
Sex: Female, Male
Sex: Female, Male(Participants)Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 0.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 2.4 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 3.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 4.8 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg WeeklyTrastuzumab-MCC-DM1 1.6 mg/kg WeeklyTrastuzumab-MCC-DM1 2.0 mg/kg WeeklyTrastuzumab-MCC-DM1 2.4 mg/kg WeeklyTrastuzumab-MCC-DM1 2.9 mg/kg WeeklyTotal
Female311115333316352
Male000000000000
Region of Enrollment
Region of Enrollment(participants)Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 0.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 2.4 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 3.6 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 4.8 mg/kg Every 3 WeeksTrastuzumab-MCC-DM1 1.2 mg/kg WeeklyTrastuzumab-MCC-DM1 1.6 mg/kg WeeklyTrastuzumab-MCC-DM1 2.0 mg/kg WeeklyTrastuzumab-MCC-DM1 2.4 mg/kg WeeklyTrastuzumab-MCC-DM1 2.9 mg/kg WeeklyTotal
United States311115333316352
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Study locations

No study locations are listed for this record.

09

References and documents

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 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 26, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT00932373
Lead sponsor
Genentech, Inc.
Responsible party
Sponsor
First posted
Jul 3, 2009
Start date
Apr 2006
Primary completion
Jun 2009
Completion
Jun 2009
Results posted
Jul 30, 2015
Last update
Aug 26, 2015

Study contacts

Scott Holden, M.D.
study director · Genentech, Inc.
View the source record on ClinicalTrials.gov ↗

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