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

NCT00932373 | Completed Phase 1 Results

• 1 other identifier: TDM3569g
• Study Type: interventional
• Target: 54
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Metastatic Breast Cancer

Keywords

HER2-positive breast cancer; MBC; Trastuzumab emtansine; Herceptin; T-DM1

Outcome Measures

Primary Outcomes (6)

• 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.

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

• 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

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

• Maximum Tolerated Dose (MTD)

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

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

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

  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

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

  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

• 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.

  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)

• Percentage of Participants With an Objective Response

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

• Duration of Objective Response

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

• Progression-free Survival

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

• Percentage of Participants With Anti-therapeutic Antibodies to Trastuzumab Emtansine

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

Study Arms (1)

1

EXPERIMENTAL

Drug: trastuzumab-MCC-DM1

Interventions

trastuzumab-MCC-DM1 DRUG

Intravenous escalating dose

1

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Related Publications (1)

• 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.

  PMID: 22648179 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Genentech, Inc.

genentech@druginfo.com

800 821-8590

Study Officials

• Scott Holden, M.D.

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2009
• First Posted: July 3, 2009
• Study Start: April 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: August 26, 2015
• Results First Posted: July 30, 2015

Record last verified: 2015-08