Human epidermal growth factor receptor 2 (HER2) overexpressing solid tumors specifically metastatic urothelial bladder cancer (MUBC) as well as pancreas/cholangio cancer, which are locally advanced or have spread to other tissues and organs. MedDRA version: 19.0 Level: LLT Classification code 10033575 Term: Pancreas cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.0 Level: LLT Classification code 10046721 Term: Urothel
Conditions
Sponsors
Roche Farma, S.A. que representa en España a F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically centrally confirmed HER2-positive (Immunohistochemistry [IHC] 3+ in >= 30% of tumor cells): locally advanced, metastatic or unresectable (not treatable with curative intent) urothelial bladder cancer (UBC) or pancreas/cholangio cancer - There must be no standard treatment options available for patients with the above HER2 overexpressing tumors and they must have undergone at least one prior platinum-based treatment for inoperable, locally advanced or metastatic tumor (Note: for pancreas/cholangio cancer, prior treatments are NOT required to be platinum-based.) - The patient must have evaluable disease fulfilling all of the following imaging criteria: • On diagnostic computed tomography (CT) scan/ magnetic resonance imaging (MRI): lesion should be measurable according to RECIST 1.1 • Target lesion(s) should not have been previously irradiated - At least one formalin-fixed paraffin-embedded biopsy of the primary tumor and/or from a metastatic site is required - Age >= 18 years - Eastern cooperative oncology group (ECOG) performance status of 0-1 - No significant cardiac history and a current left ventricular ejection fraction (LVEF) >= 50%. LVEF should be determined within 28 days before the start of trastuzumab emtansine treatment - Adequate organ function - Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule - Negative serum pregnancy test for women of childbearing potential (including pre-menopausal women who have had a tubal ligation) and for all women not meeting the definition of postmenopausal (12 months of amenorrhea), and who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy - For women of childbearing potential and men with partners of childbearing potential, agreement by the patient and/or partner to use a highly effective non-hormonal form of contraception such as surgical sterilization or two effective forms of non-hormonal contraception until 7 months after the last dose of trastuzumab emtansine - Life expectancy of at least 12 weeks. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 56
Exclusion criteria
Exclusion criteria: - Patients with previous exposure to HER2-targeted therapies in any setting - Patients showing histologically confirmed focal HER2-expression, i.e., 150 mmHg and/or diastolic 100 mmHg) - Current unstable angina pectoris - History of symptomatic congestive heart failure (CHF) of any New York Heart Association criteria or ventricular arrhythmia that requires treatment - History of myocardial infarction within the last 6 months - Peripheral neuropathy, Grade >= 3 - Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy - Current severe, uncontrolled systemic disease - History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, stage I uterine cancer, or other cancers with a similar outcome as those previously mentioned - For female patients, current pregnancy and lactation - Concurrent, serious, uncontrolled infections or current known infection with human immunodeficiency virus, active hepatitis B and/or hepatitis C - Known prior severe hypersensitivity to trastuzumab and trastuzumab emtansine or the excipients of the investigational medicinal product - Clinically significant bleeding within 30 days before enrollment - Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment - Concurrent participation in any other therapeutic clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of trastuzumab emtansine by best overall response rate (BOR) as determined by the investigator (using response evaluation criteria in solid tumors [RECIST] 1.1).;Secondary Objective: • To evaluate the efficacy of trastuzumab emtansine by progression free survival (PFS) as determined by the investigator (using RECIST 1.1) and overall survival (OS) • To evaluate the safety of trastuzumab emtansine • To evaluate the immune response to trastuzumab emtansine • To identify biomarkers that are predictive of response, can provide evidence of trastuzumab emtansine activity, or can increase the knowledge and understanding of disease biology.;Primary end point(s): 1. BOR (Best overall response rate) as determined by the investigator (using RECIST 1.1). BOR is defined as the best response recorded from the first day of study treatment until disease progression/recurrence or death.;Timepoint(s) of evaluation of this end point: 1. The total length of the study for an individual cohort, from screening of the first patient to the end of the study, is expected to be approximately 3 years (18 months of recruitment, 6 months of treatment and 12 months of follow-up). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) PFS (Progression-free survival), defined as the time from beginning of treatment to the first occurrence of disease progression, as determined by the investigator (using RECIST 1.1), or death from any cause, whichever occurs first 2) OS (Overall survival), defined as the time from beginning of treatment to death from any cause 3) Incidence, type and severity of all adverse events (AEs) and serious adverse events 4) Incidence and type of AEs leading to discontinuation, modification, or delay of trastuzumab emtansine dose 5) Changes in vital signs, physical examination findings, and clinical laboratory results 6) Number of deaths and its causes 7) Cases of drug-induced liver injury meeting Hy’s Law criteria 8) Pneumonitis of all grades 9) Change in LVEF over the course of the study as measured by echocardiogram or multiple-gated acquisition scan 10) Incidence of CHF 11) Incidence of anti-therapeutic antibodies (ATAs) during the study relative to the prevalence of ATAs at baseline 12) Exploratory assessment of immune checkpoint-inhibitors and infiltrating lymphocytes in the tumor before and after treatment by the assessment of immune-related biomarkers such as programmed T-cell death ligand-1 (PDL1) and cluster of differentiation 8 (CD8) 13) To evaluate the HER2 status by immunohistochemistry (IHC) and in situ hybridization (ISH) 14) Correlate levels of HER2 protein expression, HER2 gene amplification and circulating HER2 extracellular domain (HER2 ECD) to trastuzumab emtansine efficacy 15) Evaluate biomarkers that may be associated with response and/or safety on the protein, ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) level.;Timepoint(s) of evaluation of this end point: 1-15. The total length of the study for an individual cohort, from screening of the first patient to the end of the study, is expected to be approximately 3 years (18 months of recruitment, 6 months of treatment and 12 months of follow-up). | — |
Countries
Netherlands, Slovakia, Spain
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed