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

NCT ID: NCT00934856

Last Updated: 2017-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2013-10-31

Brief Summary

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.

Conditions

Breast Cancer

Study Design

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

Study Groups

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

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.

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Docetaxel will be administered on Day 1 of each 3-week cycle at a dose specified in the respective arms (as per summary of product characteristics \[SmPC\]).

Trastuzumab emtansine

Intervention Type: DRUG

T-DM1 will be administered on Day 1 or Day 2 of each 3-week cycle at a dose specified in the respective arms.

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

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.

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Docetaxel will be administered on Day 1 of each 3-week cycle at a dose specified in the respective arms (as per summary of product characteristics \[SmPC\]).

Trastuzumab emtansine

Intervention Type: DRUG

T-DM1 will be administered on Day 1 or Day 2 of each 3-week cycle at a dose specified in the respective arms.

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

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.

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Docetaxel will be administered on Day 1 of each 3-week cycle at a dose specified in the respective arms (as per summary of product characteristics \[SmPC\]).

Trastuzumab emtansine

Intervention Type: DRUG

T-DM1 will be administered on Day 1 or Day 2 of each 3-week cycle at a dose specified in the respective arms.

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

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.

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Docetaxel will be administered on Day 1 of each 3-week cycle at a dose specified in the respective arms (as per summary of product characteristics \[SmPC\]).

Trastuzumab emtansine

Intervention Type: DRUG

T-DM1 will be administered on Day 1 or Day 2 of each 3-week cycle at a dose specified in the respective arms.

LABC: T-DM1 + Doc (Doublet Regimen)

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.

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Docetaxel will be administered on Day 1 of each 3-week cycle at a dose specified in the respective arms (as per summary of product characteristics \[SmPC\]).

Trastuzumab emtansine

Intervention Type: DRUG

T-DM1 will be administered on Day 1 or Day 2 of each 3-week cycle at a dose specified in the respective arms.

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

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.

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Docetaxel will be administered on Day 1 of each 3-week cycle at a dose specified in the respective arms (as per summary of product characteristics \[SmPC\]).

Pertuzumab

Intervention Type: DRUG

Pertuzumab at a loading dose of 840 mg IV infusion on Day 1 of Cycle 1 followed by maintenance dose of 420 mg IV infusion on Day 1 of each 3-week cycle.

Trastuzumab emtansine

Intervention Type: DRUG

T-DM1 will be administered on Day 1 or Day 2 of each 3-week cycle at a dose specified in the respective arms.

Interventions

Docetaxel

Docetaxel will be administered on Day 1 of each 3-week cycle at a dose specified in the respective arms (as per summary of product characteristics \[SmPC\]).

Intervention Type: DRUG

Pertuzumab

Pertuzumab at a loading dose of 840 mg IV infusion on Day 1 of Cycle 1 followed by maintenance dose of 420 mg IV infusion on Day 1 of each 3-week cycle.

Intervention Type: DRUG

Trastuzumab emtansine

T-DM1 will be administered on Day 1 or Day 2 of each 3-week cycle at a dose specified in the respective arms.

Intervention Type: DRUG

Other Intervention Names

T-DM1

Eligibility Criteria

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

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

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Charlotte, North Carolina, United States

Houston, Texas, United States

Dijon, , France

Saint-Herblain, , France

Barcelona, Barcelona, Spain

Madrid, Madrid, Spain

Madrid, Madrid, Spain

Dundee, , United Kingdom

Countries

United States; France; Spain; United Kingdom

References

Martin M, Fumoleau P, Dewar JA, Albanell J, Limentani SA, Campone M, Chang JC, Patre M, Strasak A, de Haas SL, Xu J, Garcia-Saenz JA. Trastuzumab emtansine (T-DM1) plus docetaxel with or without pertuzumab in patients with HER2-positive locally advanced or metastatic breast cancer: results from a phase Ib/IIa study. Ann Oncol. 2016 Jul;27(7):1249-56. doi: 10.1093/annonc/mdw157. Epub 2016 Apr 6.

Reference Type: DERIVED

PMID: 27052654 (View on PubMed)

Other Identifiers

2009-010000-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BP22572

Identifier Type: -

Identifier Source: org_study_id