Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2014-001056-28 | EudraCT Number |
Not provided
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| Name | Class |
|---|---|
| Roche Pharma AG | INDUSTRY |
| Experior | INDUSTRY |
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The primary goal is to determine the maximum tolerated dose (MTD) of the combination of T-DM1 and non-pegylated liposomal doxorubicin in metastatic breast cancer (mBC) patients previously treated with taxanes and trastuzumab-based therapy.
In addition, pharmacokinetic data on the combination of T-DM1 and liposomal doxorubicin will be obtained.
Subjects: Age ≥ 18 years with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer that have relapsed or progressed on or after taxanes and trastuzumab-based therapy. Subjects must have histologic or cytologic confirmation of the HER2-positive metastatic breast cancer. Evidence of measurable or evaluable metastatic disease is required.
Primary objective:
Secondary objectives:
Type of study: This is a prospective dose-finding, multicenter and open-label phase I clinical trial.
Treatment: Trastuzumab emtansine (T-DM1) will be administered at a fixed dose of 3.6 mg/kg IV on Day 1 every 3 weeks and three cohorts of patients with three different dose levels of conventional non-pegylated liposomal doxorubicin (45 mg/m2, 50 mg/m2 and 60 mg/m2) IV on Day 1 in cycles of 21 days each are planned.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental arm | Experimental | Trastuzumab emtansine (T-DM1) will be administered at a fixed dose of 3.6 mg/kg IV on Day 1 every 3 weeks and three cohorts of patients with three different dose levels of conventional non-pegylated liposomal doxorubicin (45 mg/m2, 50 mg/m2 and 60 mg/m2) IV |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Trastuzumab and non-pegylated liposomal doxorubicin | Drug | 3 Cohorts (3+3 design): Cohort 1- Trastuzumab 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin (45 mg/m2) IV Cohort 2- Trastuzumab 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin (50 mg/m2) IV Cohort 3- Trastuzumab 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin (60 mg/m2) IV |
| Measure | Description | Time Frame |
|---|---|---|
| Hematological - Dose Limiting Toxicities | Treatment-related adverse events (AEs) of any grade reported in ≥10% of patients. | Baseline up to 6 weeks after patient entry (Cycle2Day21) |
| Non-Hematological - Dose Limiting Toxicities | Treatment-related AEs of any grade reported in ≥10% of patients. | Baseline up to 6 weeks after patient entry (Cycle2Day21) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate | Patients with best overall response of confirmed complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST criteria guidelines (version 1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR |
Not provided
Inclusion Criteria:
Signed informed consent
Patient able and willing to comply with protocol
Cytologically or histologically confirmed carcinoma of the breast.
Incurable locally advanced or metastatic disease who have previously received up to two previous chemotherapy regimens in this setting. Patient must have progressed or relapsed on or after taxane and trastuzumab-based therapy.
HER2-positive disease
At least one measurable lesion according to RECIST version 1.1; or patients with non measurable lesions could be included with these exceptions:
o patients with only blastic bone lesions / with only pleural, peritoneal or cardiac effusion, or meningeal carcinomatosis
≥ 18 years of age
Eastern Cooperative Oncology Group (ECOG) 0 or 1
Life expectancy ≥ 3 months
Adequate bone marrow function:
Adequate hepatic and renal function
Adequate cardiovascular function with LVEF ≥ 55%
Recovery from all reported toxicities of previous anti-cancer therapies to baseline or grade ≤ 1 (CTCAE version 4.0), except for alopecia
For women of childbearing potential and not postmenopausal, and who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy, and men with partners of childbearing potential, use of forms of contraception
Exclusion Criteria:
Previous treatment with T-DM1 or anthracyclines
More than two chemotherapeutic regimens for locally advanced incurable disease or metastatic disease
Prior anti-cancer treatment with chemotherapy, immunotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin-C), hormonal therapy or lapatinib within 7 days, prior trastuzumab within 21 days (7 days if weekly trastuzumab) or any other targeted therapy within the last 21 days prior to starting study treatment
Previous radiotherapy for the treatment of unresectable, locally advanced/recurrent or mBC is not allowed if:
History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to the active substance or to any of the excipients of T-DM1 or non-pegylated liposomal doxorubicin
Patients with central nervous system (CNS) involvement. However, patients with metastatic CNS tumors may participate in this trial if the patient is > 4 weeks from radiotherapy completion, is clinically stable with respect to CNS tumor at the time of study entry and is not receiving steroid therapy for brain metastases
Severe/uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
Cardiopulmonary dysfunction
Current peripheral neuropathy of Grade ≥ 3 per the NCI CTCAE, v4.0
History of a decrease in LVEF to < 40% or symptomatic congestive heart failure (CHF) with previous trastuzumab treatment
Prior malignancy, other than carcinoma in situ of the cervix, or non-melanoma skin cancer, unless the prior malignancy was cured ≥ 5 years before first dose of study drug with no subsequent evidence of recurrence
Current known active infection with HIV, hepatitis B, and/or hepatitis C virus
Women who are pregnant or breast-feeding
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| Name | Affiliation | Role |
|---|---|---|
| Javier Cortés, MD | Hospital Ramon y Cajal, Madrid, Spain | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| MedSIR investigative site | Paris | 75020 | France | |||
| MedSIR investigative site |
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| ID | Title | Description |
|---|---|---|
| FG000 | Period 1: Cohort 1, Trastuzumab + Doxorubicin (45 mg/m2) | Trastuzumab emtansine (T-DM1) will be administered at a fixed dose of 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin at a dose level of 45 mg/m2. |
| FG001 | Period 2: Cohort 2, Trastuzumab + Doxorubicin (50 mg/m2) | Trastuzumab emtansine (T-DM1) will be administered at a fixed dose of 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin at a dose level of 50 mg/m2. |
| FG002 | Period 3: Cohort 3, Trastuzumab + Doxorubicin (60 mg/m2) | Trastuzumab emtansine (T-DM1) will be administered at a fixed dose of 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin at a dose level of 60 mg/m2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1, Trastuzumab + Doxorubicin (45 mg/m2) | Trastuzumab and non-pegylated liposomal doxorubicin: Trastuzumab 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin (45 mg/m2) IV |
| BG001 | Cohort 2, Trastuzumab + Doxorubicin (50 mg/m2) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Hematological - Dose Limiting Toxicities | Treatment-related adverse events (AEs) of any grade reported in ≥10% of patients. | Posted | Number | participants | Baseline up to 6 weeks after patient entry (Cycle2Day21) |
|
Baseline up to 24 months after patient entry
Not provided
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1, Trastuzumab + Doxorubicin (45 mg/m2) | Trastuzumab and non-pegylated liposomal doxorubicin: Trastuzumab 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin (45 mg/m2) IV |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infections and infestations | Gastrointestinal disorders | Systematic Assessment | Appendicitis |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asthenia | General disorders | Systematic Assessment | Weakness or lack of energy. |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Scientific director | Medica Scientia Innovation Research (MEDSIR) | +34 93 221 41 35 | trialsregister.medsir@medsir.org |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 27, 2017 | May 3, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 13, 2019 | Apr 22, 2021 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068878 | Trastuzumab |
| D000080044 | Ado-Trastuzumab Emtansine |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Baseline up to 24 months after patient entry |
| Best Overall Response | Patients with best overall response of confirmed complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST criteria guidelines (version 1.1) | Baseline up to 24 months after patient entry |
| Clinical Benefit Rate | Clinical benefit rate (CBR) is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) lasting more than 24 weeks based on local investigator's assessment | Baseline up to 24 months after patient entry |
| Progression-free Survival | Patients with progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or measurable increase in a non-target lesion, or the appearance of new lesions | Baseline up to 24 months after patient entry |
| Grade 3/4 Adverse Events, SAEs, Deaths and Discontinuations | Patients with grade 3/4 adverse events, Serious Adverse Events (SAEs), deaths and discontinuations | Baseline up to 24 months after patient entry |
| Discontinuation of the Study Drugs Due to Any Cardiotoxicity | Rate of patients who discontinued treatment due to Cardiac Function or Due to Cardiac Cause | Baseline up to 24 months after patient entry |
| Left Ventricular Dysfunction Class IV | New York Heart Association grading of Level II cardiotoxicities characterized by dose-independent reversible myocardial damage. The classes used in this system, I to IV with I indicating less severity and higher numbers indicating greater severity. | Baseline up to 24 months after patient entry |
| Serum HER-2 Levels | Serum human epidermal growth factor receptor 2 (HER-2) Levels (ng/mL) - Cycle 1 Day 1 and Cycle 4 Day 1. | Baseline and after 4 cycles of treatment (Cycle4Day21) |
| Doxorubicinol - Concentration (Cmax) | Plasma concentration of Doxorubicinol using a validated liquid chromatography electrospray tandem mass spectrometry (LC-MS/MS) method | Baseline (Cycle1Day1) and end of Cycle 2 (C2D21) |
| Doxorubicinol - Area Under Curve (AUC) | Area under the plasma concentration versus time curve for the pharmacokinetic parameters for doxorubicinol by treatment dose level | Baseline (Cycle1Day1) and end of Cycle 2 (C2D21) |
| Doxorubicinol - Apparent Half-life (t1/2) | Apparent half-life for doxorubicinol by treatment dose level. | Baseline (Cycle1Day1) and end of Cycle 2 (C2D21) |
| Doxorubicinol - Tmax | Maximum concentration of drug in plasma (Tmax) | Baseline (Cycle1Day1) and end of Cycle 2 (C2D21) |
| Trastuzumab - Cmax | Pharmacokinetic parameters for trastuzumab | Baseline (Cycle1 Day1) |
| Trastuzumab - AUC | Pharmacokinetic parameters for trastuzumab | Baseline (Cycle1Day1) |
| Trastuzumab - Tmax | Pharmacokinetic parameters for trastuzumab | Baseline (Cycle1Day1) |
| DM-1 - Cmax | Pharmacokinetic parameters for emtansine (DM1) by treatment dose level | Baseline (Cycle1Day1) |
| DM-1 - AUC | Pharmacokinetic parameters for DM1 by treatment dose level | Baseline (Cycle1Day1) |
| DM-1 - Tmax | Pharmacokinetic parameters for DM1 by treatment dose level | Baseline (Cycle1Day1) |
| Paris |
| 92210 |
| France |
| MedSIR investigative site | Barcelona | 00835 | Spain |
| MedSIR investigative site | Madrid | 08035 | Spain |
Trastuzumab and non-pegylated liposomal doxorubicin: Trastuzumab 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin (50 mg/m2) IV |
| BG002 | Cohort 3, Trastuzumab + Doxorubicin (60 mg/m2) | Trastuzumab and non-pegylated liposomal doxorubicin: Trastuzumab 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin (60 mg/m2) IV |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ECOG Performance Status (ITT) | Eastern Cooperative Oncology Group (ECOG) criteria used by doctors and researchers to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient. ECOG 0 (Fully active) > ECOG 5 (Dead). | Number | participants |
|
| Prior Medication | History of patients treatment that may be concomitant to study treatment, or may limit current treatment. | Count of Participants | Participants |
|
| Estrogen Receptor (ER) (ITT) | Count of Participants | Participants |
|
| Progesterone Receptor (PgR) (ITT) | Count of Participants | Participants |
|
| Human Epidermal Growth Factor Receptor 2 (HER2) (ITT) | Count of Participants | Participants |
|
| HER2 detection method | Count of Participants | Participants |
|
| TNM Staging (ITT) | A system to describe the amount and spread of cancer in a patient's body (T= primary tumor size and nature, N= regional lymph node involvement, M= level of metastasis). | Count of Participants | Participants |
|
| TNM Staging T Category | T-staging= primary tumor size, location, and nature. Tx means no information, T0= no evidence of tumor. T1-4= Increasing size/location/nature. | Count of Participants | Participants |
|
| TNM Staging N Category | N-staging= spread of tumor into local lymph nodes. Nx means no information, N0= no local involvement. N1-3= Increasing spread into lymph nodes. | Count of Participants | Participants |
|
| TNM Staging M Category | M-staging= tumor spread to distant organs or tissues. Mx means no information available. M0= No evidence of spread detected, M1= cancer detected in distant organs or tissues. | Count of Participants | Participants |
|
| Disease Stage at Initial Diagnostic | Clinical staging is based on information gained up to the initial definitive treatment. Pathologic staging includes clinical information and information obtained from pathologic examination of resected primary and regional lymph nodes. A higher cancer stage, i.e., Stage IV, is more aggressive and typically more difficult to treat. | Count of Participants | Participants |
|
| Metastasis sites (ITT) | Number | participants |
|
| Previous Treatment for Metastatic Breast Cancer | Count of Participants | Participants |
|
| OG002 | Cohort 3, Trastuzumab + Doxorubicin (60 mg/m2) | Trastuzumab and non-pegylated liposomal doxorubicin: Trastuzumab 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin (60 mg/m2) IV |
|
|
| Primary | Non-Hematological - Dose Limiting Toxicities | Treatment-related AEs of any grade reported in ≥10% of patients. | Posted | Number | participants | Baseline up to 6 weeks after patient entry (Cycle2Day21) |
|
|
|
| Secondary | Overall Response Rate | Patients with best overall response of confirmed complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST criteria guidelines (version 1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR | Best Overall Response (percentage of participants) with confirmed complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST v1.1 criteria guidelines | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline up to 24 months after patient entry |
|
|
|
| Secondary | Best Overall Response | Patients with best overall response of confirmed complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST criteria guidelines (version 1.1) | Best Overall Response, n (%) | Posted | Count of Participants | Participants | Baseline up to 24 months after patient entry |
|
|
|
| Secondary | Clinical Benefit Rate | Clinical benefit rate (CBR) is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) lasting more than 24 weeks based on local investigator's assessment | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline up to 24 months after patient entry |
|
|
|
| Secondary | Progression-free Survival | Patients with progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or measurable increase in a non-target lesion, or the appearance of new lesions | Posted | Median | 95% Confidence Interval | months | Baseline up to 24 months after patient entry |
|
|
|
| Secondary | Grade 3/4 Adverse Events, SAEs, Deaths and Discontinuations | Patients with grade 3/4 adverse events, Serious Adverse Events (SAEs), deaths and discontinuations | Posted | Number | participants | Baseline up to 24 months after patient entry |
|
|
|
| Secondary | Discontinuation of the Study Drugs Due to Any Cardiotoxicity | Rate of patients who discontinued treatment due to Cardiac Function or Due to Cardiac Cause | Posted | Count of Participants | Participants | Baseline up to 24 months after patient entry |
|
|
|
| Secondary | Left Ventricular Dysfunction Class IV | New York Heart Association grading of Level II cardiotoxicities characterized by dose-independent reversible myocardial damage. The classes used in this system, I to IV with I indicating less severity and higher numbers indicating greater severity. | Posted | Count of Participants | Participants | Baseline up to 24 months after patient entry |
|
|
|
| Secondary | Serum HER-2 Levels | Serum human epidermal growth factor receptor 2 (HER-2) Levels (ng/mL) - Cycle 1 Day 1 and Cycle 4 Day 1. | Posted | Mean | Standard Deviation | ng/mL | Baseline and after 4 cycles of treatment (Cycle4Day21) |
|
|
|
| Secondary | Doxorubicinol - Concentration (Cmax) | Plasma concentration of Doxorubicinol using a validated liquid chromatography electrospray tandem mass spectrometry (LC-MS/MS) method | Posted | Mean | Standard Deviation | μg/mL | Baseline (Cycle1Day1) and end of Cycle 2 (C2D21) |
|
|
|
| Secondary | Doxorubicinol - Area Under Curve (AUC) | Area under the plasma concentration versus time curve for the pharmacokinetic parameters for doxorubicinol by treatment dose level | Posted | Mean | Standard Deviation | ng x h/mL | Baseline (Cycle1Day1) and end of Cycle 2 (C2D21) |
|
|
|
| Secondary | Doxorubicinol - Apparent Half-life (t1/2) | Apparent half-life for doxorubicinol by treatment dose level. | Posted | Mean | Standard Deviation | days | Baseline (Cycle1Day1) and end of Cycle 2 (C2D21) |
|
|
|
| Secondary | Doxorubicinol - Tmax | Maximum concentration of drug in plasma (Tmax) | Posted | Median | Full Range | hours | Baseline (Cycle1Day1) and end of Cycle 2 (C2D21) |
|
|
|
| Secondary | Trastuzumab - Cmax | Pharmacokinetic parameters for trastuzumab | Posted | Mean | Standard Deviation | μg/mL | Baseline (Cycle1 Day1) |
|
|
|
| Secondary | Trastuzumab - AUC | Pharmacokinetic parameters for trastuzumab | Posted | Mean | Standard Deviation | μg x h/mL | Baseline (Cycle1Day1) |
|
|
|
| Secondary | Trastuzumab - Tmax | Pharmacokinetic parameters for trastuzumab | Posted | Mean | Full Range | hours | Baseline (Cycle1Day1) |
|
|
|
| Secondary | DM-1 - Cmax | Pharmacokinetic parameters for emtansine (DM1) by treatment dose level | Posted | Mean | Standard Deviation | μg/mL | Baseline (Cycle1Day1) |
|
|
|
| Secondary | DM-1 - AUC | Pharmacokinetic parameters for DM1 by treatment dose level | Posted | Mean | Standard Deviation | μg x h/mL | Baseline (Cycle1Day1) |
|
|
|
| Secondary | DM-1 - Tmax | Pharmacokinetic parameters for DM1 by treatment dose level | Posted | Median | Full Range | hours | Baseline (Cycle1Day1) |
|
|
|
| 1 |
| 3 |
| 1 |
| 3 |
| 3 |
| 3 |
| EG001 | Cohort 2, Trastuzumab + Doxorubicin (50 mg/m2) | Trastuzumab and non-pegylated liposomal doxorubicin: Trastuzumab 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin (50 mg/m2) IV | 1 | 3 | 0 | 3 | 3 | 3 |
| EG002 | Cohort 3, Trastuzumab + Doxorubicin (60 mg/m2) | Trastuzumab and non-pegylated liposomal doxorubicin: Trastuzumab 3.6 mg/kg IV on Day 1 every 3 weeks and non-pegylated liposomal doxorubicin (60 mg/m2) IV | 0 | 9 | 1 | 9 | 9 | 9 |
|
| Investigations | Blood and lymphatic system disorders | Systematic Assessment | Aspartate aminotransferase increased |
|
| Nervous system disorders | Nervous system disorders | Systematic Assessment | Nervous system disorder |
|
| Nervous system disorder | Nervous system disorders | Systematic Assessment | Partial seizures |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Mucosal inflammation | General disorders | Systematic Assessment |
|
| Gait disturbance | General disorders | Systematic Assessment | Walking abnormally compared to usual. |
|
| Pyrexia | General disorders | Systematic Assessment |
|
| Neutrophil count decreased | Blood and lymphatic system disorders | Systematic Assessment |
|
| Platelet count decreased | Blood and lymphatic system disorders | Systematic Assessment |
|
| Aspartate aminotransferase (AST) increased | Blood and lymphatic system disorders | Systematic Assessment |
|
| Alanine aminotransferase (ALT) increased | Blood and lymphatic system disorders | Systematic Assessment |
|
| Brain natriuretic peptide increased | Cardiac disorders | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Hepatobiliary disorders | Systematic Assessment |
|
| Troponin increased | Cardiac disorders | Systematic Assessment |
|
| White blood cell count decreased | Blood and lymphatic system disorders | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Hepatobiliary disorders | Systematic Assessment | Can also be caused by bile duct obstruction, gallbladder disease, or bone disorders |
|
| Haemoglobin decreased | Blood and lymphatic system disorders | Systematic Assessment |
|
| Lymphocyte count decreased | Blood and lymphatic system disorders | Systematic Assessment |
|
| Alanine aminotransferase abnormal | Hepatobiliary disorders | Systematic Assessment |
|
| Blood albumin decreased | Metabolism and nutrition disorders | Systematic Assessment |
|
| Blood alkaline phosphatase abnormal | Hepatobiliary disorders | Systematic Assessment |
|
| Platelet count abnormal | Blood and lymphatic system disorders | Systematic Assessment |
|
| Gastrointestinal disorders | Gastrointestinal disorders | Systematic Assessment |
|
| Metabolism and nutrition disorders | Metabolism and nutrition disorders | Systematic Assessment |
|
| Skin and subcutaneous tissue disorders | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Blood and lymphatic system disorders | Blood and lymphatic system disorders | Systematic Assessment |
|
| Eye disorders | Eye disorders | Systematic Assessment |
|
| Nervous system disorders | Nervous system disorders | Systematic Assessment |
|
| Respiratory, thoracic and mediastinal disorders | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hepatobiliary disorders | Hepatobiliary disorders | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | Systematic Assessment |
|
| Hyperacusis | Ear and labyrinth disorders | Systematic Assessment |
|
| Vulvovaginal dryness | Reproductive system and breast disorders | Systematic Assessment |
|
| Hot flush | Vascular disorders | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | Systematic Assessment | Lack of adequate healthy red blood cells |
|
| Headache | Nervous system disorders | Systematic Assessment | Sensory pain in any region of the head |
|
Not provided
Not provided
| D017437 |
| Skin and Connective Tissue Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D008453 | Maytansine |
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| Title | Measurements |
|---|---|
|
| Inc. aspartate aminotransferase |
|
| Inc. alanine aminotransferase |
|
| Inc. brain natriuretic peptide |
|
| Inc. gamma-glutamyl transferasehemoglobin |
|
| Increased troponin Ilymphocyte count |
|
| Decreased appetite |
|
| Alopecia |
|
| Epistaxis |
|
| Rhinorrhea |
|
| Headache |
|
| Fatigue |
|
| Mucosal inflammation |
|
| Inc. blood alkaline phosphatase |
|
| Aphthous ulcer |
|
| Constipation |
|
| Diarrhea |
|
| Dry mouth |
|
| Gingival bleeding |
|
| Vomiting |
|
| Hypoalbuminemia |
|
| Rash |
|
| Stable disease <24 weeks |
|
| Progressive disease |
|
| Not evaluable |
|
| Title | Measurements |
|---|---|
|
| Leukopenia |
|
| Lymphopenia |
|
| Increase in aspartate aminotransferase (AST) |
|
| Fatigue |
|
|
|
|
|
|