Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Behaviors and Mental Disorders

Breast Neoplasms

Behavior, Addictive

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Trastuzumab

Pertuzumab

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Pertuzumab and trastuzumab FDC subcutaneous, A loading dose of 1200 mg pertuzumab and 600 mg trastuzumab followed by a maintenance dose of 600 mg pertuzumab and 600 mg; day 1 of each 3 week cycle during 5 neoadjuvant cycles and 13 adjuvant cycles if complete response

Pertuzumab and trastuzumab FDC subcutaneous

80 mg/m2, day 1,8,15 of each 3 week cycle during 4 cycles

3,6 mg/kg, 14 adjuvant cycles if not complete response

TDM1

Adjuvant endocrine therapy will be administered as per local practice and according to recognized clinical practice guidelines

Endocrine therapy

Omission of surgery and sentinel lymph node dissection in patients with HER2-E and ERBB2 high breast cancer who achieving a complete response following standard anti-HER2-based neoadjuvant therapy with paclitaxel/trastuzumab/pertuzumab

Omission surgery

Nuria Chic, MD

Aleix Pratts

This is a prospective, single arm, open-label, exploratory study in women with primary operable HER2-positive, HER2-enriched(HER2-E)/ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression), to evaluate the omission of surgery and sentinel lymph node dissection in patients with HER2-E and ERBB2 high breast cancer who achieving a complete response following standard anti-HER2-based neoadjuvant therapy with paclitaxel/trastuzumab/pertuzumab.

Omission of Surgery and Sentinel Lymph Node Dissection in Clinically Low-risk HER2positive Breast Cancer With High HER2 Addiction and a Complete Response Following Standard Anti- HER2-based Neoadjuvant Therapy (ELPIS Trial)

To estimate the loco-regional invasive disease-free survival at 3-year of patients who achieve a complete response based on imaging and a stereotactic-guided vacuum-assisted breast biopsy, and omit loco-regional surgery. 3-years loco-regional invasive disease-free survival rate is defined as time from the first date of no disease (i.e., date of stereotaxic guided biopsy) to loco-regional recurrence. Loco-regional recurrence is defined as recurrence of breast cancer in the same breast parenchyma as the original primary lesion, the axilla, regional lymph nodes, chest wall and/or skin of the ipsilateral breast.

European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30), version 3; 3.2 EORTC QLQ-BR23 (breast cancer-specific questionnaire). There are all scale with a range that goes from 0 to 100 were 0 is the worst result and 100 the best.

Fundacion Clinic per a la Recerca Biomédica

David Garcia Cinca

Clinical Trial Manager

Symptoms and General Pathology

Rare Diseases

Neoplasm Metastasis

Neoplastic Processes

Myotonic Dystrophy Type 1

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Docetaxel

Ado-Trastuzumab Emtansine

Maytansine

Adenosine

Immunotoxins

Immunoconjugates

Immunologic Factors

Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) administered over 30-90 minutes every 3 weeks on Day 1 of each 21-day cycle.

Patients received a loading dose of trastuzumab 8 mg/kg IV + docetaxel 75 or 100 mg/m\^2 IV on Day 1 of Cycle 1 followed by trastuzumab 6 mg/kg IV + docetaxel 75 or 100 mg/m\^2 IV on Day 1 of all subsequent 21-day cycles.

The total dose depended on the patient's weight on Day 1 of each cycle. Trastuzumab emtansine was administered every 3 weeks until investigator-assessed radiographic or clinical progressive disease (or until second disease progression for patients who crossed over), unacceptable toxicity, or study closure, whichever occurred first.

Trastuzumab emtansine [Kadcyla]

The dose of trastuzumab was recalculated if body weight changed by more than ±10% from baseline. Trastuzumab was administered every 3 weeks until investigator-assessed radiographic or clinical progressive disease, or unmanageable toxicity. Patients in the trastuzumab + docetaxel arm who discontinued study treatment because of progressive disease were eligible to cross-over to trastuzumab emtansine treatment until a second progressive disease event, clinical deterioration, and/or intolerance.

Docetaxel was given at a dose of 75 or 100 mg/m\^2 based on the investigator's decision. Patients in the trastuzumab + docetaxel arm who discontinued study treatment because of progressive disease were eligible to cross-over to trastuzumab emtansine treatment until a second progressive disease event, clinical deterioration, and/or intolerance.

Ellie Guardino, MD/PhD

This was a Phase II, randomized, multicenter, international, 2-arm, open-label clinical trial designed to explore the efficacy and safety of trastuzumab emtansine (T-DM1) relative to the combination of trastuzumab and docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive, unresectable, locally advanced breast cancer and/or metastatic breast cancer who have not received prior chemotherapy for metastatic disease.

A Study of the Efficacy and Safety of Trastuzumab Emtansine (Trastuzumab-MCC-DM1) vs. Trastuzumab (Herceptin®) and Docetaxel (Taxotere®) in Patients With Metastatic HER2-positive Breast Cancer Who Have Not Received Prior Chemotherapy for Metastatic Disease

A Randomized, Multicenter, Phase ii Study of the Efficacy and Safety of Trastuzumab-MCC-DM1 vs. Trastuzumab (Herceptin®) and Docetaxel (Taxotere®) in Patients With Metastatic HER2-positive Breast Cancer Who Have Not Received Prior Chemotherapy for Metastatic Disease

PFS was defined as the time from randomization (R) to first documented investigator-assessed radiographic or clinical disease progression (PD) or death due to any cause, whichever occurred first. For target lesions (TL), PD was defined as at least a 20% increase in the sum of the longest diameter (SLD) of TLs, taking as reference the SLD recorded since treatment started or the appearance of 1 or more new lesions. For non-TLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. Data for patients without PD or death were censored at the last date of tumor assessment prior to crossover (or, if no tumor assessment was performed after Baseline, at the R date +1 day). Data for patients who were lost to follow-up were censored at the last date of tumor assessment prior to crossover at which the patient was known to be progression free. Data for patients with no post-baseline tumor assessment were censored at the R date +1 day.

Overall survival was defined as the time from randomization to the date of death from any cause. Patients who were alive at the time of analysis were censored at the date on which they were last known to be alive. Patients with no post-baseline were censored at the date of randomization plus 1 day.

A patient had an objective response if they had a complete response or a partial response on 2 consecutive occasions ≥ 4 weeks apart. For target lesions, a complete response was defined as the disappearance of all target lesions; a partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. For non-target lesions, a complete response was defined as the disappearance of all non-target lesions; a partial response was defined as the persistence of 1 or more non-target lesions.

Duration of objective response was defined as the time from initial response to investigator-assessed radiographic or clinical disease progression or death on study from any cause. For target lesions, disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, disease progression was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Target lesions should be selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions.

CB was defined as an objective response (complete response \[CR\], partial response \[PR\]) or stable disease (SD) for 6 months after randomization. For target lesions (TL), CR=the disappearance of all TL; PR=at least a 30% decrease in the sum of the longest diameter (LD) of TL, taking as reference the baseline sum LD; SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started; PD=at least a 20% increase in the sum of the LD of TL, taking as reference the smallest sum of the LD recorded since the treatment started or the appearance of 1 or more new lesions. For non-TL, CR=the disappearance of all non-TL; PR=the persistence of 1 or more non-TL; SD=the persistence of 1 or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits; PD=the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TL.

Time to symptom progression was defined as the time from randomization to the first documentation of a ≥ 5-point decrease from baseline in the Trial Outcome Index-Physical/Functional/Breast (TOI-PFB) subscale score of the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire. The FACT-B questionnaire is a valid and reliable measure of symptoms associated with breast cancer. The TOI-PFB is a 24-item subscale generated using 3 subsections (Physical Well-Being \[7 items\], Functional Well-Being \[7 items\], and Additional Concerns \[10 items\]) from the FACT-B questionnaire. Patients responded to each item on a scale of 0-4 (Not at all-Very much). The total score ranged from 0 to 96. A higher score indicates fewer symptoms. A positive change score indicates improvement.

Serum samples were collected from all 67 patients enrolled in the trastuzumab emtansine arm using sparse pharmacokinetic sampling. Blood samples were collected prior to dosing and 30 minutes post-infusion of trastuzumab emtansine at Cycles 1 and 5. Serum samples were assayed for trastuzumab emtansine and total trastuzumab (sum of unconjugated trastuzumab and emtansine conjugated to trastuzumab) in indirect sandwich ELISAs. The area under the concentration-time curve (AUC) was estimated based on non-compartmental analysis using WinNonlin (Version 5.2.1) software.

Plasma samples were collected from all 67 patients in the trastuzumab emtansine group 30 minutes post-infusion of trastuzumab emtansine at Cycles 1 and 5. The plasma samples were assayed for free emtansine in a mass-spectrometric assay.

Hoffmann-La Roche

Safety population: All randomized patients who received at least 1 dose of study treatment. In the trastuzumab + docetaxel (T+D) group, 2 patients received no treatment and 2 patients received a dose of trastuzumab emtansine (TE) and were included in that group for safety analyses, resulting in 66 patients in the T+D group and 69 in the TE group.

Trastuzumab Emtansine

Trastuzumab + Docetaxel

Total

Age, Continuous

Sex: Female, Male

Medical Communications

Intent-to-treat population: All randomized patients.

Progression-free Survival (PFS) by the Investigator Using Modified Response Evaluation Criteria In Solid Tumors (RECIST)

Overall Survival

All randomized patients with measureable disease at Baseline.

Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)

All randomized patients with measureable disease at Baseline. Only patients with an objective response were included in the analysis.

Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)

All randomized patients with measurable disease at Baseline.

Clinical Benefit (CB) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)

All randomized patients with a Baseline and at least 1 post-Baseline valid score.

Time to Symptom Progression

Trastuzumab emtansine Cycle 1 (n=62)

Trastuzumab emtansine Cycle 5 (n=39)

Total trastuzumab Cycle 1 (n=60)

Total trastuzumab Cycle 5 (n=38)

Trastuzumab Emtansine 3.6 mg/kg

Pharmacokinetic evaluable population: Patients who had adequate concentration-time data to estimate at least 1 pharmacokinetic parameter.

Serum Concentrations (Area Under the Concentration-time Curve [AUC]) of Trastuzumab Emtansine and Total Trastuzumab

Cycle 1 (n=62)

Cycle 5 (n=39)

Plasma Concentration of Free Emtansine

Overall Study

Nervous System Diseases

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

T-DM1 (First injection day 1) followed by brain sequential RT (start day D3), second injection T-DM1 day 22.

Brain sequential RT (start day 1) followed by T-DM1 (First injection day 15), second injection T-DM1 day 36.

Brain sequential RT (start day 1) followed by T-DM1 (First injection day 22), second injection T-DM1 day 43.

T-DM1 (First injection day 1) followed by brain sequential and concomitant RT (start day D18), second injection T-DM1 day 22.

administration of the TDM1 by IV perfusion

Brain Sequential RT

David AZRIA

The purpose of this study is to determine the optimal sequences of combined trastuzumab emtansine (T-DM1) and whole-brain radiotherapy in patients presenting brain metastases from HER2-positive breast cancer in terms of acute toxicities and blood/cerebrospinal fluid T-DM1 pharmacokinetics.

Patients With Brain Metastases From HER2-positive Breast Cancer

A Phase I Study to Evaluate the Feasibility of Different Sequences of Combined Trastuzumab Emtansine (T-DM1) and Whole-brain Radiotherapy in Patients With Brain Metastases From HER2-positive Breast Cancer

To determine the optimal sequences of combined trastuzumab emtansine (T-DM1) and whole-brain radiotherapy in patients presenting brain metastases from HER2-positive breast cancer in terms of acute toxicities and blood/cerebrospinal fluid T-DM1 pharmacokinetics.

Objective responses (complete and partial response) by MRI according to the RECIST criteria (v1.1) and volumetric assessment

Institut du Cancer de Montpellier - Val d'Aurelle

Disease Progression

Disease Attributes

Mitogens

Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.

From Cycle 4, participants with early progressive disease (demonstrated prior to the end of Cycle 6) could receive combined pertuzumab and trastuzumab emtansine. Pertuzumab was administered after trastuzumab emtansine by IV infusion at a loading dose of 840 mg on Day 1, starting at the cycle after tumor progression was determined, followed by 420 mg IV infusion every 3 weeks in subsequent cycles.

Participants who met criteria for ongoing clinical benefit were allowed to continue study treatment in the absence of disease progression or unacceptable toxicity for up to 1 year.

pertuzumab

Steve Olsen, M.D.

This is a multicenter, open-label, single-arm Phase II study designed to evaluate the effect of T-DM1 on the duration of corrected QT (QTc) interval in patients with HER2-positive locally advanced or metastatic breast cancer and to make preliminary assessments regarding the safety, tolerability, and efficacy of combined T-DM1 and pertuzumab in patients with early disease progression.

The QT interval is a measure of time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. The QTcF interval is the QT interval as calculated using Fridericia's correction; the QTcB interval is the QT interval as calculated using Bazett's correction.

Corrected QT Interval Effects of Trastuzumab Emtansine (T-DM1) in Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer and the Safety and Tolerability of Combined T-DM1 and Pertuzumab in Patients With Early Disease Progression

A Phase II, Open-Label Study to Evaluate Corrected QT Interval Effects of Trastuzumab-MCC-DM1 (T-DM1) in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer and to Evaluate the Safety and Tolerability of Combined T-DM1 and Pertuzumab in Patients With Early Disease Progression While Receiving T-DM1 Alone

The QT interval is a measure of time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. The corrected QT interval was calculated using Fridericia's correction (QTcF) from electrocardiogram (ECG) data. Each participant had triplicate QTcF intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline QTcF interval was subtracted from the average QTcF intervals to create a baseline-adjusted average QTcF interval.

The corrected QT interval was calculated using Bazett's correction (QTcB) from electrocardiogram (ECG) data. Each participant had triplicate QTcB intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline QTcB interval was subtracted from the average QTcB intervals to create a baseline-adjusted average QTcB interval.

The uncorrected QT interval was calculated from electrocardiogram (ECG) data. Each participant had triplicate QT intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline QT interval was subtracted from the average QT intervals to create a baseline-adjusted average QT interval.

The PR interval is the time in seconds from the beginning of the P wave to the beginning of the QRS complex, and was calculated from electrocardiogram (ECG) data. Each participant had triplicate PR intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline PR interval was subtracted from the average PR intervals to create a baseline-adjusted average PR interval.

The QRS interval represents the time it takes for depolarization of the ventricles and was calculated from electrocardiogram (ECG) data. Each participant had triplicate QRS intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline QRS interval was subtracted from the average QRS intervals to create a baseline-adjusted average QRS interval.

The corrected QT interval was calculated using Fridericia's correction (QTcF) and using Bazett's correction (QTcB) from electrocardiogram (ECG) data. Each participant had triplicate QTc intervals measured at each timepoint and the average was calculated for each patient at each timepoint. QTc interval categories are based off International Conference on Harmonisation (ICH) Tripartite Guideline E14.

The corrected QT interval was calculated using Fridericia's correction (QTcF) and using Bazett's correction (QTcB) from electrocardiogram (ECG) data. Each participant had triplicate QTc intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline QTc interval was subtracted from the average QTc intervals to create a baseline-adjusted average QTc interval.

QTc interval categories are based off International Conference on Harmonisation (ICH) Tripartite Guideline E14.

The incidence of abnormal U-wave changes from baseline was determined based on centrally read electrocardiogram (ECG) tracings comparing each of the three triplicate readings from the post baseline ECG time points to the baseline ECG reading. At each time point, if at least one of the three triplicate readings was abnormal, the participant was counted as abnormal for that ECG timepoint as follows: a large U wave, inverted U wave, or T-U fusion compared with baseline was considered an abnormal significant change from baseline.

The incidence of abnormal T-wave changes from baseline was determined based on centrally read electrocardiogram (ECG) tracings comparing each of the three triplicate readings from the post baseline ECG time points to the baseline ECG reading. At each time point, if at least one of the three triplicate readings was abnormal, the participant was counted as abnormal for that ECG timepoint as follows: an inverted T, flat T, or biphasic T compared with baseline was considered an abnormal significant change from baseline. Additionally, nonspecific T-wave changes from baseline were considered as abnormal nonsignificant changes from baseline. T-wave changes from baseline due to ventricular conduction or left ventricular hypertrophy strain were considered not evaluable. C=Cycle; D=Day.

Objective response was defined as a complete response (CR) or partial response (PR) determined on two consecutive assessments conducted by the investigator ≥ 4 weeks apart. Responses were assessed by physical examination and imaged-based evaluation using a modified version of the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0:

CR-the disappearance of all target lesions and the disappearance of all nontarget lesions and normalization of tumor marker level and no new lesions.

PR-either the disappearance of all target lesions with persistence of one or more nontarget lesion(s) and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter with no new lesions or unequivocal progression of existing nontarget lesions.

In patients with an objective response during the single-agent trastuzumab emtansine treatment period, duration of response was defined as the time from the first documented objective response to the time of first documented disease progression or death, whichever occurred first. Progressive disease was defined as either at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study with an absolute increase of at least 5 mm, or the appearance of one or more new lesions, or the unequivocal progression of existing nontarget lesions.

If a patient did not die or experience disease progression before the end of the study, duration of response was censored at the day of the last tumor assessment when the patient was known to be progression free.

Progression-free survival (PFS) was defined as the time from the first day of study treatment (Day 1) to first documented disease progression or death, whichever occurred first. If a patient did not experience disease progression or die, PFS was censored at the day of the last tumor assessment that a patient was known to be progression free.

Participants were considered to have experienced clinical benefit if they had an objective response or maintained stable disease for at least 6 months from start of study treatment. Objective response was defined as a complete or partial response determined on two consecutive tumor assessments at least 4 weeks apart based on a modified version of RECIST.

Stable disease was defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started and no new lesions or unequivocal progression of existing nontarget lesions.

An serious AE is any AE that is fatal, life threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product(s), or is considered a significant medical event by the investigator (e.g., may jeopardize the patient or may require medical/surgical intervention to prevent one of the outcomes listed above).

The severity of each AE was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0, or as follows: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Very severe; Grade 5 = Death related to AE.

Left ventricular ejection fraction (LVEF) was assessed on the basis of local assessments of echocardiogram or multigated acquisition scan (MUGA) data. A decrease in LVEF is defined as a decrease from Baseline of greater than or equal to 15%.

Grade 3 LVEF is an ejection fraction between 20 and 40%.

Serum samples were quantitated for T-DM1 (DM1 conjugated to trastuzumab) levels in a validated assay using an indirect sandwich enzyme-linked immunosorbent assay (ELISA). The minimum quantifiable concentration in human serum was 40 ng/mL. Serum samples were assayed for total trastuzumab (conjugated and unconjugated T-DM1) in a validated assay using an indirect sandwich ELISA method; the minimum quantifiable concentration in human serum was 40 ng/mL.

Area under the serum concentration-time curve from Time zero to time of last measurable concentration (AUClast) for T-DM1 (conjugated trastuzumab) and Total Trastuzumab (conjugated and unconjugated T-DM1) at Cycle 1 and Cycle 3.

Area under the serum concentration-time curve from Time zero extrapolated to infinity (AUCinf) for T-DM1 (conjugated trastuzumab) and total trastuzumab (conjugated and unconjugated T-DM1) at Cycle 1.

The number of participants with anti-T-DM1 antibodies was assessed using a validated bridging antibody enzyme-linked immunosorbent assay (ELISA).

Genentech, Inc.

Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.

Single-Agent T-DM1 Treatment

Participants who received combined pertuzumab and trastuzumab emtansine. Pertuzumab was administered after trastuzumab emtansine by IV infusion at a loading dose of 840 mg on Day 1, followed by 420 mg IV infusion every 3 weeks in subsequent cycles.

T-DM1 + Pertuzumab

Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.

From Cycle 4, participants with early Progressive disease (demonstrated prior to the end of Cycle 6) could receive combined pertuzumab and trastuzumab emtansine. Pertuzumab was administered after trastuzumab emtansine by IV infusion at a loading dose of 840 mg on Day 1, starting at the cycle after tumor progression was determined, followed by 420 mg IV infusion every 3 weeks in subsequent cycles.

Participants who met criteria for ongoing clinical benefit were allowed to continue study treatment in the absence of disease progression or unacceptable toxicity for up to 1 year.

T-DM1 / T-DM1 + Pertuzumab

Age Continuous

United States

Region of Enrollment

Cycle 1, Day 1, 15 minutes post-dose [N=44]

Cycle 1, Day 1, 60 minutes post-dose [N=45]

Cycle 1, Day 8 [N=43]

Cycle 3, Day 1, 15 minutes pre-dose [N=35]

Cycle 3, Day 1, 15 minutes post-dose [N=37]

Cycle 3, Day 1, 60 minutes post-dose [N=37]

T-DM1

ECG-evaluable population consisted of patients who received T-DM1, had at least 1 interpretable pre-T-DM1 ECG measurement recorded on Cycle 1 Day 1, had at least 1 interpretable post-T-DM1 ECG measurement and who were not treated with medications that may have altered cardiac conduction. N indicates the ECG-evaluable population at each time point.

Change From Baseline in Mean Duration of the QTc Interval

ECG-Evaluable population; N indicates the ECG-evaluable population with available data at each time point.

Change From Baseline in Mean Duration of the QTc Interval Using Bazett's Correction

Cycle 1 Day 1, 15 minutes post-dose [N=44]

Cycle 1 Day 1, 60 minutes post-dose [N=45]

Cycle 1 Day 8 [N=43]

Cycle 3 Day 1, 15 minutes pre-dose [N=35]

Cycle 3 Day 1, 15 minutes post-dose [N=37]

Cycle 3 Day 1, 60 minutes post-dose [N=37]

Change From Baseline in Uncorrected QT Interval

Change From Baseline in PR Interval

Change From Baseline in QRS Duration

ECG-evaluable population; N indicates the ECG-evaluable population with available data at each time point.

Change From Baseline in Heart Rate

QTcF: Cycle 1, Day 1, 15 minutes post-dose [N=44]

QTcF: Cycle 1, Day 1, 60 minutes post-dose [N=45]

QTcF: Cycle 1, Day 8 [N=43]

QTcF: Cycle 3, Day 1, 15 minutes pre-dose [N=35]

QTcF: Cycle 3, Day 1, 15 minutes post-dose [N=37]

QTcF: Cycle 3, Day 1, 60 minutes post-dose [N=37]

QTcB: Cycle 1, Day 1, 15 minutes post-dose [N=44]

QTcB: Cycle 1, Day 1, 60 minutes post-dose [N=45]

QTcB: Cycle 1, Day 8 [N=43]

QTcB: Cycle 3, Day 1, 15 minutes pre-dose [N=35]

QTcB: Cycle 3, Day 1, 15 minutes post-dose [N=37]

QTcB: Cycle 3, Day 1, 60 minutes post-dose [N=37]

Participants with an average QTc interval less than or equal to 450 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.

Average QTc Interval ≤ 450 ms

Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.

Average QTc Interval > 450 to ≤ 480 ms

Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.

Average QTc Interval > 480 to ≤ 500 ms

Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.

Average QTc Interval > 500 ms

The number of participants analyzed for each QTc interval category represents the total treated population. N indicates the ECG-evaluable population with available data at each time point.

Percentage of Participants Within Each Absolute QTc Interval Category

Participants with an average Baseline-adjusted QTc interval less than or equal to 30 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Omission of Surgery and Sentinel Lymph Node Dissection in Clinically Low-risk HER2positive Breast Cancer With High HER2 Addiction and a Complete Response Following Standard Anti- HER2-based Neoadjuvant Therapy (ELPIS Trial)	NCT04301375	Mammary Cancer	Pertuzumab and ... Paclitaxel TDM1 Endocrine thera... Omission surger...	40 Years -	Hospital Clinic of Barcelona
A Study of the Efficacy and Safety of Trastuzumab Emtansine (Trastuzumab-MCC-DM1) vs. Trastuzumab (Herceptin®) and Docetaxel (Taxotere®) in Patients With Metastatic HER2-positive Breast Cancer Who Have Not Received Prior Chemotherapy for Metastatic Disease	NCT00679341	Breast Cancer	Trastuzumab emt... Trastuzumab Docetaxel	18 Years -	Hoffmann-La Roche
Patients With Brain Metastases From HER2-positive Breast Cancer	NCT02135159	HER2-positive B...	TDM1 Brain Sequentia...	18 Years -	Institut du Cancer de Montpellier - Val d'Aurelle
Corrected QT Interval Effects of Trastuzumab Emtansine (T-DM1) in Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer and the Safety and Tolerability of Combined T-DM1 and Pertuzumab in Patients With Early Disease Progression	NCT00943670	Metastatic Brea...	pertuzumab Trastuzumab emt...	18 Years -	Genentech, Inc.
Patients With Brain Metastases From HER2-positive Breast Cancer	NCT02135159	HER2-positive B...	TDM1 Brain Sequentia...	18 Years -	Institut du Cancer de Montpellier - Val d'Aurelle
Omission of Surgery and Sentinel Lymph Node Dissection in Clinically Low-risk HER2positive Breast Cancer With High HER2 Addiction and a Complete Response Following Standard Anti- HER2-based Neoadjuvant Therapy (ELPIS Trial)	NCT04301375	Mammary Cancer	Pertuzumab and ... Paclitaxel TDM1 Endocrine thera... Omission surger...	40 Years -	Hospital Clinic of Barcelona

Spots Global Cancer Trial Database for tdm1

Every month we try and update this database with for tdm1 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for tdm1

Every month we try and update this database with for tdm1 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for tdm1 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.