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

NCT ID: NCT00875979

Last Updated: 2013-12-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2011-08-31

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.

Detailed Description

There were 2 phases in the study, a Dose Escalation phase (Phase 1b) and a Dose Expansion phase (Phase 2a). In the Dose Escalation phase, 3 patients were enrolled at the first dose level (3.0 mg/kg trastuzumab emtansine) and and 6 patients were enrolled at the second dose level (3.6 mg/kg trastuzumab emtansine). An additional 58 patients were enrolled at the 3.6 mg/kg trastuzumab emtansine dose level in the Dose Expansion phase (Phase 2a) of the study.

Conditions

Metastatic Breast Cancer

Keywords

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Trastuzumab emtansine 3.0 mg/kg + pertuzumab 420 mg

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.

Group Type: EXPERIMENTAL

Trastuzumab emtansine [Kadcyla] 3.0 mg/kg

Intervention Type: DRUG

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

Pertuzumab 420 mg

Intervention Type: DRUG

Pertuzumab was provided as a single-use formulation.

Trastuzumab emtansine 3.6 mg/kg + pertuzumab 420 mg

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.

Group Type: EXPERIMENTAL

Trastuzumab emtansine [Kadcyla] 3.6 mg/kg

Intervention Type: DRUG

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

Pertuzumab 420 mg

Intervention Type: DRUG

Pertuzumab was provided as a single-use formulation.

Interventions

Trastuzumab emtansine [Kadcyla] 3.0 mg/kg

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

Intervention Type: DRUG

Trastuzumab emtansine [Kadcyla] 3.6 mg/kg

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

Intervention Type: DRUG

Pertuzumab 420 mg

Pertuzumab was provided as a single-use formulation.

Intervention Type: DRUG

Other Intervention Names

trastuzumab-DM1; trastuzumab-MCC-DM1; T-DM1; trastuzumab-DM1; trastuzumab-MCC-DM1; T-DM1; Perjeta

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elaine K. Wong, M.Sc., M.D.

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

Boca Raton, Florida, United States

Deerfield Beach, Florida, United States

Maywood, Illinois, United States

Indianapolis, Indiana, United States

Wichita, Kansas, United States

Rockville, Maryland, United States

Chapel Hill, North Carolina, United States

Philadelphia, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Nashville, Tennessee, United States

Brussels, , Belgium

Vancouver, British Columbia, Canada

Montreal, Quebec, Canada

Paris, , France

Villejuif, , France

Cologne, , Germany

Aviano, , Italy

Milan, , Italy

Barcelona, , Spain

Valencia, , Spain

Countries

United States; Belgium; Canada; France; Germany; Italy; Spain

References

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.

Reference Type: DERIVED

PMID: 24733796 (View on PubMed)

Other Identifiers

TDM4373g

Identifier Type: OTHER

Identifier Source: secondary_id

BO22495

Identifier Type: -

Identifier Source: org_study_id