A Study of Trastuzumab Emtansine (Trastuzumab-MCC-DM1, T-DM1) in Combination With Pertuzumab Administered to Patients With Human Epidermal Growth Factor Receptor-2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer Who Have Previously Received Trastuzumab

NCT00875979 | Completed Phase 1 Results

• 2 other identifiers: BO22495TDM4373g
• Study Type: interventional
• Target: 67
• Locations: 7 countries
• Sites: 20

Brief Summary

This was a multi-institutional, multinational, open-label, single-arm Phase Ib/II study designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of trastuzumab emtansine (trastuzumab-MCC-DM1) administered by intravenous (IV) infusion in combination with pertuzumab in patients with human epidermal growth factor receptor-2 (HER2)-positive locally advanced or metastatic breast cancer who had previously received trastuzumab.

Conditions

Metastatic Breast Cancer

Keywords

MBC; Breast Cancer; HER2+; HER2+ breast cancer; HER2 positive breast cancer; herceptin; Trastuzumab emtansine

Outcome Measures

Primary Outcomes (1)

• Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)

  A patient had an objective response if they had a complete response or a partial response on 2 consecutive occasions ≥ 4 weeks apart. For target lesions, a complete response was defined as the disappearance of all target lesions; 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 longest diameter. For non-target lesions, a complete response was defined as the disappearance of all non-target lesions; a partial response was defined as the persistence of 1 or more non-target lesions.

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

Secondary Outcomes (2)

• Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)

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

• Progression-free Survival Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)

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

Study Arms (2)

Trastuzumab emtansine 3.0 mg/kg + pertuzumab 420 mg

EXPERIMENTAL

Patients received trastuzumab emtansine 3.0 mg/kg intravenously (IV) on Day 1 of every 3 week cycle until progressive disease, intolerable toxicity, initiation of another anti-cancer therapy, or patient discontinuation. Patients also received a loading dose of 840 mg of pertuzumab IV on Day 1 of Cycle 1 followed by pertuzumab 420 mg IV on Day 1 of every subsequent 3 week cycle.

Drug: Trastuzumab emtansine [Kadcyla] 3.0 mg/kg; Drug: Pertuzumab 420 mg

Trastuzumab emtansine 3.6 mg/kg + pertuzumab 420 mg

EXPERIMENTAL

Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) on Day 1 of every 3 week cycle until progressive disease, intolerable toxicity, initiation of another anti-cancer therapy, or patient discontinuation. Patients also received a loading dose of 840 mg of pertuzumab IV on Day 1 of Cycle 1 followed by pertuzumab 420 mg IV on Day 1 of every subsequent 3 week cycle.

Drug: Trastuzumab emtansine [Kadcyla] 3.6 mg/kg; Drug: Pertuzumab 420 mg

Interventions

Trastuzumab emtansine [Kadcyla] 3.0 mg/kg DRUG

Trastuzumab emtansine was provided as a single-use lyophilized formulation.

Also known as: trastuzumab-DM1, trastuzumab-MCC-DM1, T-DM1

Trastuzumab emtansine 3.0 mg/kg + pertuzumab 420 mg

Trastuzumab emtansine [Kadcyla] 3.6 mg/kg DRUG

Trastuzumab emtansine was provided as a single-use lyophilized formulation.

Also known as: trastuzumab-DM1, trastuzumab-MCC-DM1, T-DM1

Trastuzumab emtansine 3.6 mg/kg + pertuzumab 420 mg

Pertuzumab 420 mg DRUG

Pertuzumab was provided as a single-use formulation.

Also known as: Perjeta

Trastuzumab emtansine 3.0 mg/kg + pertuzumab 420 mg; Trastuzumab emtansine 3.6 mg/kg + pertuzumab 420 mg

Eligibility Criteria

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

You may qualify if:

• Histologically documented human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer.
• Tumor tissue blocks or 15-20 unstained tissue slides for confirmatory central laboratory HER2 status testing and other exploratory assessments.
• Prior trastuzumab in any line of therapy.
• No prior trastuzumab emtansine (T-DM1) or pertuzumab therapy.
• Measurable disease.
• For women of childbearing potential, agreement to use an effective form of contraception and to continue its use for the duration of the study.
• Life expectancy ≥ 90 days.

You may not qualify if:

• Less than 21 days since the last anti-tumor therapy, including chemotherapy, biologic, experimental, immune, hormonal, or radiotherapy for the treatment of breast cancer, with the following exceptions: Hormone-replacement therapy or oral contraceptives; palliative radiation therapy involving ≤ 25% of marrow-bearing bone if administered ≥ 14 days prior to first study treatment.
• History of intolerance or hypersensitivity to trastuzumab and/or adverse events related to trastuzumab that resulted in trastuzumab being permanently discontinued.
• Peripheral neuropathy of Grade ≥ 2.
• History of clinically significant cardiac dysfunction.
• Current severe, uncontrolled systemic disease, eg, clinically significant cardiovascular, pulmonary, or metabolic disease.
• Brain metastases that are untreated, progressive, or have required any type of therapy to control symptoms from brain metastases within 60 days of the first study treatment.
• History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Roche Pharma AG: collaborator

Study Sites (20)

Unknown Facility

Boca Raton, Florida, 33428, United States

Location

Unknown Facility

Deerfield Beach, Florida, 33442, United States

Location

Unknown Facility

Maywood, Illinois, 60153, United States

Location

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Indianapolis, Indiana, 46202, United States

Location

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Wichita, Kansas, 67214, United States

Location

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Rockville, Maryland, 20850-3348, United States

Location

Unknown Facility

Chapel Hill, North Carolina, 27514, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 19104, United States

Location

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Philadelphia, Pennsylvania, 19111, United States

Location

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Nashville, Tennessee, 37203, United States

Location

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Brussels, 1000, Belgium

Location

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Vancouver, British Columbia, V5Z 1H5, Canada

Location

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Montreal, Quebec, H3A 1A1, Canada

Location

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Paris, 75248, France

Location

Unknown Facility

Villejuif, 94805, France

Location

Unknown Facility

Cologne, 50924, Germany

Location

Unknown Facility

Aviano, 33081, Italy

Location

Unknown Facility

Milan, 20133, Italy

Location

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Barcelona, 08035, Spain

Location

Unknown Facility

Valencia, 46010, Spain

Location

Related Publications (1)

• Miller KD, Dieras V, Harbeck N, Andre F, Mahtani RL, Gianni L, Albain KS, Crivellari D, Fang L, Michelson G, de Haas SL, Burris HA. Phase IIa trial of trastuzumab emtansine with pertuzumab for patients with human epidermal growth factor receptor 2-positive, locally advanced, or metastatic breast cancer. J Clin Oncol. 2014 May 10;32(14):1437-44. doi: 10.1200/JCO.2013.52.6590. Epub 2014 Apr 14.

  PMID: 24733796 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ado-Trastuzumab Emtansine; pertuzumab

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: Hoffmann-La Roche

800 821-8590

Study Officials

• Elaine K. Wong, M.Sc., 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: April 2, 2009
• First Posted: April 6, 2009
• Study Start: May 1, 2009
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: December 24, 2013
• Results First Posted: July 18, 2013

Record last verified: 2013-12

Locations

FR (2); DE (1); ES (2); BE (1); IT (2); CA (2); US (10)