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

NCT00934856 | Completed Phase 1 Results

• 2 other identifiers: BP225722009-010000-28
• Study Type: interventional
• Target: 98
• Locations: 4 countries
• Sites: 8

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicity (DLT) - MBC and LABC Feasibility Population

  DLTs included (as per National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] grading): Grade 4 thrombocytopenia, thrombocytopenia of any grade with concurrent hemorrhage or requiring blood platelet transfusion, or thrombocytopenia not recovered by Day 21 to at least 100,000/microliter (mcL); Grade 4 neutropenia lasting for more than 7 days; Febrile neutropenia; Grade greater than or equal to (\>/=) 3 neurotoxicity in the form of peripheral neuropathy or peripheral neurotoxicity not improving to baseline or Grade less than or equal to (\</=) 1 by Day 21; Any non-hematological toxicity of Grade \>/= 3 except for alopecia, fever, and chills, not improving to baseline or Grade \</=1 by Day 21, despite adequate toxicity management; Any subjective intolerable toxicity felt by the investigator to be related to either study treatment; Any other treatment-related toxicity prohibiting the start of the Cycle 2 on Day 22; Fulminant skin rash.

  Cycle 1 (up to 21 days)

• Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs) - MBC and LABC Population

  An AE is any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.

  Baseline up to 28 days after last dose for MBC participants and for LABC participants who could not undergo surgery, and up to 6 weeks post-surgery for LABC participants who underwent surgery (maximum up to approximately 3 years)

Secondary Outcomes (28)

• Percentage of Participants With Progression-Free Survival (PFS) Event - MBC Population

  Baseline until disease progression or death (up to approximately 3 years)

• PFS - MBC Population

  Baseline until disease progression or death (up to approximately 3 years)

• Percentage of Participants With a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) - MBC Population

  Baseline until disease progression or recurrence (up to approximately 3 years)

• Percentage of Participants With Treatment Failure - MBC Population

  Baseline until end of treatment (up to 39.8 months)

• Time to Treatment Failure (TTF) - MBC Population

  Baseline until end of treatment (up to 39.8 months)

Study Arms (6)

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

EXPERIMENTAL

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.

Drug: Docetaxel; Drug: Trastuzumab emtansine

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

EXPERIMENTAL

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.

Drug: Docetaxel; Drug: Trastuzumab emtansine

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

EXPERIMENTAL

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.

Drug: Docetaxel; Drug: Trastuzumab emtansine

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

EXPERIMENTAL

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.

Drug: Docetaxel; Drug: Trastuzumab emtansine

LABC: T-DM1 + Doc (Doublet Regimen)

EXPERIMENTAL

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.

Drug: Docetaxel; Drug: Trastuzumab emtansine

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

EXPERIMENTAL

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.

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

Interventions

Docetaxel 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 \[SmPC\]).

LABC: T-DM1 + Doc (Doublet Regimen); LABC: T-DM1 + Doc + Pertuzumab (Triplet Regimen); MBC: T-DM1 2.4 mg/kg + Doc 60 mg/m^2 (over 2 days); MBC: T-DM1 2.4 mg/kg + Doc 60 mg/m^2 (same day); MBC: T-DM1 2.4 mg/kg + Doc 75 mg/m^2 (over 2 days); MBC: T-DM1 3.6 mg/kg + Doc 60 mg/m^2 (same day)

Pertuzumab 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.

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

Trastuzumab emtansine 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.

Also known as: T-DM1

LABC: T-DM1 + Doc (Doublet Regimen); LABC: T-DM1 + Doc + Pertuzumab (Triplet Regimen); MBC: T-DM1 2.4 mg/kg + Doc 60 mg/m^2 (over 2 days); MBC: T-DM1 2.4 mg/kg + Doc 60 mg/m^2 (same day); MBC: T-DM1 2.4 mg/kg + Doc 75 mg/m^2 (over 2 days); MBC: T-DM1 3.6 mg/kg + Doc 60 mg/m^2 (same day)

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (8)

Unknown Facility

Charlotte, North Carolina, 28203, United States

Location

Unknown Facility

Houston, Texas, 77005, United States

Location

Unknown Facility

Dijon, 21079, France

Location

Unknown Facility

Saint-Herblain, 44805, France

Location

Unknown Facility

Barcelona, Barcelona, 08003, Spain

Location

Unknown Facility

Madrid, Madrid, 28007, Spain

Location

Unknown Facility

Madrid, Madrid, 28040, Spain

Location

Unknown Facility

Dundee, DD1 9SY, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 27052654 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Docetaxel; pertuzumab; Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Maytansine; Macrolides; Lactones; 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

global-roche-genentech-trials@gene.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2009
• First Posted: July 8, 2009
• Study Start: July 1, 2009
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: April 6, 2017
• Results First Posted: April 6, 2017

Record last verified: 2017-02

Locations

FR (2); ES (3); US (2); GB (1)