Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Myotonic Dystrophy Type 1

Antineoplastic Agents

All Drugs and Chemicals

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Docetaxel

Ado-Trastuzumab Emtansine

Trastuzumab

Pertuzumab

Mitogens

Maytansine

Adenosine

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Immunologic Factors

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.

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.

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.

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.

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.

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.

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 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.

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

Trastuzumab emtansine

Clinical Trials

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.

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

An Open-Label, Multi-Center Phase I/II Study of the Safety and Tolerability of the Combination of Trastuzumab-MCC-DM1 (T-DM1) With Docetaxel, and Potentially Pertuzumab, for Treatment for Patients With Advanced Breast Cancer

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.

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.

PFS was defined as the time interval between the date of the start of treatment and the date of first documentation of progressive disease (PD) or death from any cause, whichever occurred first. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 (v1.0). For target lesions (TLs), PD was at least a 20 percent (%) increase in the sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more lesions. For non-target lesions (NTLs), PD was the appearance of one or more new lesions and/or unequivocal progression of existing NTLs. Data for participants without PD or death was censored at the time of the last response assessment. Percentage of participants with PFS event was calculated as the (number of participants with PFS event \[PD or death\]) divided by (total number of participants), and then multiplied by 100.

PFS was defined as the time interval between the date of the start of treatment and the date of first documentation of PD or death from any cause, whichever occurred first. Response was based on RECIST v1.0. For TLs, PD was at least a 20 % increase in the sum of LD of TLs, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more lesions. For NTLs, PD was the appearance of one or more new lesions and/or unequivocal progression of existing NTLs. Median PFS time was calculated using Kaplan-Meier estimates. Data for participants without PD or death was censored at the time of the last response assessment.

BOR was defined as CR or PR recorded from baseline until disease progression/recurrence according to RECIST v1.0 criteria. For TLs, CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the sum of LDs of the TLs, taking as a reference the baseline (BL) sum of LDs. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. Percentage of participants with BOR rate was calculated as the (number of participants with CR or PR) divided by (total number of participants), and then multiplied by 100. The 95% confidence interval (Cl) was determined using the Pearson-Clopper method.

Treatment failure was defined as the discontinuation of treatment for any reason, including the following qualifying events: PD, death from any cause, withdrawal from study treatment, or initiation of nonprotocol anti-cancer therapy. Percentage of participants with treatment failure was calculated as the (number of participants with treatment failure) divided by (total number of participants), and then multiplied by 100.

TTF was defined as the time interval between the date of start of treatment and the date of PD, death from any cause, withdrawal from study treatment, or initiation of non-protocol anti-cancer therapy, whichever occurred first. Participants without an event at the time of the analysis were censored at the date of the last follow-up assessment. Median TTF was estimated using the Kaplan-Meier method.

CBR was defined as percentage of participants experiencing SD of at least 6 months from the start of treatment plus CR or PR according to the RECIST v1.0 criteria. For TLs: CR- disappearance of all TLs. PR- at least 30% decrease in the sum of LDs of the TLs, taking as a reference the BL sum of LDs. PD- at least 20% increase in the sum of LD of TLs, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more lesions. SD- neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. For NTLs: CR- disappearance of all NTLs and normalization of tumor marker levels. SD- persistence of one or more NTLs and/or maintenance of tumor marker level above the normal limits. Percentage of participants= number of participants with CR/PR/SD divided by total number of participants, and then multiplied by 100. 95% CI was determined using the Pearson-Clopper method.

Duration of response was calculated for participants with CR or PR based on the RECIST v1.0 criteria. Duration of response was defined as the time interval between the date the CR or PR was first recorded and the date on which PD was first noted or date of death, whichever occurred first. Participants with no documented PD after CR or PR were censored at the last date at which they were known to have had the CR or PR, respectively. Median duration of response was estimated using the Kaplan-Meier method.

The pCR was defined as the absence of invasive neoplastic cells at microscopic examination of the tumor remnants and lymph nodes after surgery following primary systemic therapy.

BOR was defined as CR or PR recorded from baseline until disease progression/recurrence according to RECIST v1.0 criteria. For TLs, CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the sum of LDs of the TLs, taking as a reference the baseline (BL) sum of LDs. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. Percentage of participants with BOR rate was calculated as the (number of participants with CR or PR) divided by (total number of participants), and then multiplied by 100. The 95% Cl was determined using the Pearson-Clopper method.

Number of participants with ATA response was reported. Data for this outcome measure was planned to be reported for overall MBC and LABC participants and not by individual treatment arms.

DM1 is the metabolite of trastuzumab emtansine.

Docetaxel infusion duration = 1 hr (as per summary of product characteristics \[SmPC\])

Docetaxel infusion duration = 1 hr (as per SmPC)

Hoffmann-La Roche

All participants who received at least one dose of study medication were included.

Feasibility part: Participants with HER2-positive MBC received docetaxel 75 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 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 was stopped and T-DM1 2.4 mg/kg was continued until confirmed evidence of disease progression, unacceptable toxicity, or withdrawal of participant consent.

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

Feasibility part: Participants with HER2-positive MBC received 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 was stopped and T-DM1 2.4 mg/kg was continued until confirmed evidence of disease progression, unacceptable toxicity, or withdrawal of participant consent.

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

Feasibility part: Participants with HER2-positive MBC received 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 was stopped and T-DM1 2.4 mg/kg was continued until confirmed evidence of disease progression, unacceptable toxicity, or withdrawal of participant consent.

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

Feasibility and extension part: Participants with HER2-positive MBC received 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 was stopped and T-DM1 3.6 mg/kg was continued until confirmed evidence of disease progression, unacceptable toxicity, or withdrawal of participant consent.

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

Feasibility and extension part: Participants with HER2-positive LABC received 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 was administered for up to 6 cycles or until unacceptable toxicity, and prior to surgery.

LABC: T-DM1 + Doc (Doublet Regimen)

Feasibility and extension part: Participants with HER2-positive LABC received 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 was administered for up to 6 cycles or until unacceptable toxicity, and prior to surgery.

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

Total

Age, Continuous

Sex: Female, Male

Medical Communications

Participants with HER2-positive MBC received docetaxel 75 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 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 was stopped and T-DM1 2.4 mg/kg was continued until confirmed evidence of disease progression, unacceptable toxicity, or withdrawal of participant consent.

Participants with HER2-positive MBC received 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 was stopped and T-DM1 2.4 mg/kg was continued until confirmed evidence of disease progression, unacceptable toxicity, or withdrawal of participant consent.

Participants with HER2-positive MBC received 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 was stopped and T-DM1 2.4 mg/kg was continued until confirmed evidence of disease progression, unacceptable toxicity, or withdrawal of participant consent.

Participants with HER2-positive MBC received 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 was stopped and T-DM1 3.6 mg/kg was continued until confirmed evidence of disease progression, unacceptable toxicity, or withdrawal of participant consent.

Participants with HER2-positive LABC received 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 was administered for up to 6 cycles or until unacceptable toxicity, and prior to surgery.

Participants with HER2-positive LABC received 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 was administered for up to 6 cycles or until unacceptable toxicity, and prior to surgery.

MBC and LABC feasibility population: All participants who received at least one dose of study medication and included in the feasibility part of the study.

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

SAEs

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

Participants with MBC who were enrolled in the study and who received at least one dose of study medication

Overall MBC Participants

MBC population: All participants with MBC who received at least one dose of study medication were included.

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

PFS - MBC Population

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

Percentage of Participants With Treatment Failure - MBC Population

Time to Treatment Failure (TTF) - MBC Population

Percentage of Participants With CR or PR or Stable Disease (SD) for at Least 6 Months [Clinical Benefit Rate (CBR)] - MBC Population

Duration of Response - MBC Population

LABC population: All participants with LABC who received at least one dose of study medication.

Percentage of Participants With Pathological CR (pCR) - LABC Population

Percentage of Participants With a BOR of CR or PR - LABC Population

Baseline

Post-baseline

All enrolled participants who received at least one dose of study medication

Overall MBC and LABC Participants

All participants who received at least one dose of study medication were included. Here, number analyzed=participants evaluable for ATA at specified time-point.

Number of Participants With Anti-Therapeutic Antibody (ATA) Response to Trastuzumab - MBC and LABC Population

Cycle 1

Cycle 2

All MBC participants who received T-DM1 2.4 mg/kg IV infusion.

MBC: T-DM1 2.4 mg/kg

All MBC participants who received T-DM1 3.6 mg/kg IV infusion.

MBC: T-DM1 3.6 mg/kg

All LABC participants who received T-DM1 3.6 mg/kg IV infusion.

LABC: T-DM1 3.6 mg/kg

Pharmacokinetic (PK) analysis population: PK-evaluable participants were defined as participants who received at least one dose of T-DM1 or docetaxel with at least one post-dose concentration data point. Number analyzed = participants evaluable for specified cycle for each arm.

Maximum Observed Concentration (Cmax) of Serum Trastuzumab Emtansine

PK analysis population. Overall number of participants analyzed = participants evaluable for this outcome measure. Number analyzed = participants evaluable for specified cycle for each arm.

Apparent Terminal Half-Life (t1/2) of Serum Trastuzumab Emtansine

Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) of Serum Trastuzumab Emtansine

Clearance (CL) of Serum Trastuzumab Emtansine

Volume of Distribution at Steady State (Vss) of Serum Trastuzumab Emtansine

Cmax of Total Serum Trastuzumab

t1/2 of Total Serum Trastuzumab

AUCinf of Total Serum Trastuzumab

CL of Total Serum Trastuzumab

Vss of Total Serum Trastuzumab

Cmax of Plasma N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1)

t1/2 of Plasma DM1

AUCinf of Plasma DM1

All MBC participants who received docetaxel 75 mg/m\^2 IV infusion.

MBC: Docetaxel 75 mg/m^2

All MBC participants who received docetaxel 60 mg/m\^2 IV infusion.

MBC: Docetaxel 60 mg/m^2

All LABC participants who received docetaxel 60 mg/m\^2 IV infusion.

LABC: Docetaxel 60 mg/m^2

All LABC participants who received docetaxel 75 mg/m\^2 IV infusion.

LABC: Docetaxel 75 mg/m^2

All LABC participants who received docetaxel 100 mg/m\^2 IV infusion.

LABC: Docetaxel 100 mg/m^2

Cmax of Plasma Docetaxel

t1/2 of Plasma Docetaxel

AUCinf of Plasma Docetaxel

CL of Plasma Docetaxel

Vss of Plasma Docetaxel

Feasibility part: Participants with human epidermal growth factor receptor 2 (HER2)-positive MBC received docetaxel (Doc) 75 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 and trastuzumab emtansine (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 was stopped and T-DM1 2.4 mg/kg was continued until confirmed evidence of disease progression, unacceptable toxicity, or withdrawal of participant consent.

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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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