A Study of Trastuzumab Emtansine (T-DM1) in Combination With Docetaxel, and Potentially Pertuzumab, in Participants With Advanced Breast Cancer

Roche

Status and phase: Completed; Phase 2; Phase 1

Conditions: Breast Cancer

Treatments: Drug: Pertuzumab; Drug: Trastuzumab emtansine; Drug: Docetaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT00934856

2009-010000-28 (EudraCT Number)

BP22572

Details and patient eligibility

About

This is an open-label, multi-center, non-randomized study of the safety and tolerability of the combination of T-DM1 plus docetaxel for the treatment of participants with metastatic breast cancer (MBC) and of T-DM1 plus docetaxel with or without pertuzumab, for the treatment of participants with locally advanced breast cancer (LABC). The study comprises an initial dose finding (feasibility) part to determine the maximum tolerated dose (MTD) of T-DM1 and docetaxel, followed by an extension part aiming to consolidate the safety and efficacy of the recommended docetaxel/T-DM1 combination regimen.

Enrollment: 98 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (ECOG performance status of 2 will be allowed if only due to debilitating bone disease)
• HER2-positive metastatic or locally advanced breast cancer

For MBC participants:

• Documented metastatic or inoperable locally advanced (without meeting LABC criteria) disease, amenable for treatment with docetaxel
• History of disease progression within 3 months prior to study entry

For LABC participants:

• Newly diagnosed locally advanced breast cancer, Stage IIA-IIIC (American Joint Committee on Cancer [AJCC] staging system)

Exclusion criteria

• Significant cardiac disease
• Inadequate bone marrow, liver or renal function

For MBC participants:

• Participants must not have received radiotherapy for the treatment of metastatic or locally recurrent/advanced disease other than for the relief of pain in progressing metastatic bone lesions and/or brain metastases
• Brain metastases that are untreated, symptomatic or require therapy to control symptoms; or any radiation, surgery, or other therapy to control symptoms from brain metastasis within 2 months of the first study treatment.

For LABC participants:

• Clinically or radiologically detectable metastasis (M1 disease)
• Participants for whom surgery as primary intent procedure is the best option to treat their disease
• Participants must not have received any systemic or loco-regional anti-cancer therapy for the treatment of locally advanced disease

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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98 participants in 6 patient groups

MBC: T-DM1 2.4 mg/kg + Doc 75 mg/m^2 (over 2 days)

Experimental group

Description:

Participants with human epidermal growth factor receptor 2 (HER2)-positive MBC will receive docetaxel (Doc) 75 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 and T-DM1 2.4 milligrams per kilogram (mg/kg) IV infusion on Day 2 of Cycle 1 followed by T-DM1 75 mg/m\^2 and docetaxel 2.4 mg/kg IV infusion on Day 1 of each 3-week cycle for a minimum of 6 cycles. After 6 cycles, docetaxel 75 mg/m\^2 will be stopped and T-DM1 2.4 mg/kg will be continued until confirmed evidence of disease progression, unacceptable toxicity, or withdrawal of participant consent.

Treatment:

Drug: Docetaxel

Drug: Trastuzumab emtansine

MBC: T-DM1 2.4 mg/kg + Doc 60 mg/m^2 (over 2 days)

Experimental group

Description:

Participants with HER2-positive MBC will receive docetaxel 60 mg/m\^2 IV infusion on Day 1 and T-DM1 2.4 mg/kg IV infusion on Day 2 of Cycle 1 followed by T-DM1 60 mg/m\^2 and docetaxel 2.4 mg/kg IV infusion on Day 1 of each 3-week cycle for a minimum of 6 cycles. After 6 cycles, docetaxel 60 mg/m\^2 will be stopped and T-DM1 2.4 mg/kg will be continued until confirmed evidence of disease progression, unacceptable toxicity, or withdrawal of participant consent.

Treatment:

Drug: Docetaxel

Drug: Trastuzumab emtansine

MBC: T-DM1 2.4 mg/kg + Doc 60 mg/m^2 (same day)

Experimental group

Description:

Participants with HER2-positive MBC will receive docetaxel 60 mg/m\^2 IV infusion and T-DM1 2.4 mg/kg IV infusion on Day 1 of each 3-week cycle for a minimum of 6 cycles. After 6 cycles, docetaxel 60 mg/m\^2 will be stopped and T-DM1 2.4 mg/kg will be continued until confirmed evidence of disease progression, unacceptable toxicity, or withdrawal of participant consent.

Treatment:

Drug: Docetaxel

Drug: Trastuzumab emtansine

MBC: T-DM1 3.6 mg/kg + Doc 60 mg/m^2 (same day)

Experimental group

Description:

Participants with HER2-positive MBC will receive docetaxel 60 mg/m\^2 IV infusion and T-DM1 3.6 mg/kg IV infusion on Day 1 of each 3-week cycle for a minimum of 6 cycles. After 6 cycles, docetaxel 60 mg/m\^2 will be stopped and T-DM1 3.6 mg/kg will be continued until confirmed evidence of disease progression, unacceptable toxicity, or withdrawal of participant consent.

Treatment:

Drug: Docetaxel

Drug: Trastuzumab emtansine

LABC: T-DM1 + Doc (Doublet Regimen)

Experimental group

Description:

Participants with HER2-positive LABC will receive T-DM1 3.6 mg/kg IV infusion and docetaxel 60/75/100 mg/m\^2 IV infusion on Day 1 of each 3-week cycle, for 6 cycles. Study treatment will be administered for up to 6 cycles or until unacceptable toxicity, and prior to surgery.

Treatment:

Drug: Docetaxel

Drug: Trastuzumab emtansine

LABC: T-DM1 + Doc + Pertuzumab (Triplet Regimen)

Experimental group

Description:

Participants with HER2-positive LABC will receive T-DM1 3.6 mg/kg Iv infusion, docetaxel 60/75 mg/m\^2 IV infusion, and pertuzumab 840 mg (for Cycle 1) or 420 mg (for remaining cycles) IV infusion on Day 1 of each 3-week cycle, for 6 cycles. Study treatment will be administered for up to 6 cycles or until unacceptable toxicity, and prior to surgery.

Treatment:

Drug: Docetaxel

Drug: Pertuzumab

Drug: Trastuzumab emtansine