lokaal gevorderde , gemetastaseerde of niet-curatief te behandelen urotheel blaaskanker of alvleesklier/galwegkanker (en mogelijk andere typen tumoren in een later stadium) bladder cancer cholangiocarcinoma pancreascancer
Conditions
Interventions
Trastuzumab emtansine intravenously (2.4 mg/kg, weekly or 3.6 mg/kg every 3
weeks) described in the study protocol.
HER2 positive
solid tumor
trastuzumab emtansine
Sponsors
Roche Nederland B.V.
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: * Histologically centrally confirmed HER2-positive (IHC3+ in * 30% of tumor cells): locally advanced (unresectable and not treatable with curative intent) or metastatic urothelial bladder cancer or locally advanced (unresectable and not treatable with curative intent) or metastatic 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 locally advanced (unresectable and not treatable with curative intent) inoperable, locally advanced or metastatic tumor. (Note: for pancreatic cancers/cholangiocarcinoma, prior treatments are NOT required to be platinum-based.) * The patient must have evaluable disease fulfilling all of the following imaging criteria: o On diagnostic computed tomography scan/magnetic resonance imaging: lesion should be measurable according to RECIST 1.1. o 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 performance status of 0-2. * No significant cardiac history and a current LVEF * 50%. LVEF should be determined within 28 days before the start of trastuzumab emtansine treatment. * Adequate organ function * Negative serum pregnancy test for women of childbearing potential. 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. * Signed written informed consent approved by Ethics Committee and obtained prior to any study procedure. * Life expectancy of at least 12 weeks.
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 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 (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures). * 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 (IMP). * 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 |
|---|---|
| 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the efficacy of trastuzumab emtansine by investigating Progression Free Survival (PFS) and Overall Survival (OS). In addition, the following will be investigated: Incidence and type all adverse events (AEs) and serious adverse events, Changes in vital signs, Number of deaths, Cases of drug-induced liver injury, Pneumonitis, Change in LVEF, Incidence of CHF, concentrations of trastuzumab emtansine in plasma/serum to determine exposure, Exploratory assessment of immune checkpoint-inhibitors and infiltrating lymphocytes, HER2 status , and biomarkers that may be associated with response. | — |
Countries
The Netherlands
Outcome results
None listed