Clinical trial NCT02999672: A Study to Determine Best Tumor Response With Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2 (HER2) Overexpressing Solid Tumors
Official title: Phase II, Exploratory, Multicenter, Non Randomized, Single Agent Cohort Study to Determine Best Tumor Response With Trastuzumab Emtansine in HER2 Overexpressing Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Cancer
Pancreas Cancer
Cholangiocellular Carcinoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-12-21
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This multicenter, non-randomized, Phase II study will assess the efficacy, safety, and pharmacokinetics of trastuzumab emtansine in participants with HER2 overexpressing locally advanced (unresectable and not treatable with curative intent) or metastatic urothelial bladder cancer (UBC), locally advanced (unresectable and not treatable with curative intent) or metastatic pancreatic cancer/cholangiocarcinoma with advanced disease where cure is no longer possible and where no other treatment options are available anymore. Participants will receive intravenous (IV) infusion of trastuzumab emtansine as Regimen A (2.4 milligrams per kilogram \[mg/kg\], weekly \[qw\]) or Regimen B (3.6 mg/kg, every 3 weeks \[q3w\]) until unacceptable toxicity, withdrawal of consent, disease progression (PD), or death, whichever occurs first. Based on tolerability and safety aspects, steering committee and Independent Data Monitoring Committee (iDMC) will decide on expansion of the study to include more participants with other carcinoma types.


Eligibility criteria: Inclusion Criteria:

* Histologically centrally confirmed HER2-positive (immunohistochemistry \[IHC\]3+ in greater than or equal to \[\>/=\] 30 percent \[%\] of tumor cells): locally advanced (unresectable and not treatable with curative intent), or metastatic UBC or locally advanced (unresectable and not treatable with curative intent) or metastatic pancreatic cancer/cholangiocarcinoma
* There must be no standard treatment options available for participants 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) or metastatic tumor (Note: for pancreatic cancer/cholangiocarcinoma, prior treatments are not required to be platinum-based.)
* Participant's lesion should be measurable according to RECIST V1.1 on diagnostic computed tomography (CT) scan/magnetic resonance imaging (MRI); Target lesion(s) should not have been previously irradiated
* At least one formalin-fixed paraffin-embedded (FFPE) biopsy of the primary tumor and/or from a metastatic site is required
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2
* No significant cardiac history and a current left ventricular ejection fraction (LVEF) \>/=50%
* Adequate organ function
* Life expectancy of at least 12 weeks

Exclusion Criteria:

* Participants with previous exposure to HER2-targeted therapies in any setting
* Participants showing histologically confirmed focal HER2-expression, that is, less than (\<) 30% of positively stained tumor cells
* Participants with brain metastasis as the sole site of metastatic disease and/or are symptomatic or require therapy to control symptoms
* Current uncontrolled hypertension (systolic greater than \[\>\] 150 millimeters of mercury \[mmHg\] and/or diastolic \>100 mmHg)
* Current unstable angina pectoris
* History of symptomatic congestive heart failure (CHF) of any New York Heart Association (NYHA) 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
* Concurrent, serious, uncontrolled infections or current known infection with human immunodeficiency virus (HIV), 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

Primary outcomes:
measure: Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).
timeFrame: Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)
measure: Overall Survival (OS)
timeFrame: Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)
measure: Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
timeFrame: Baseline up to approximately 18 months
measure: Percentage of Participants With Drug-induced Liver Injury Meeting Hy's Law Criteria
timeFrame: Baseline up to approximately 18 months
measure: Plasma/Serum Concentrations of Trastuzumab Emtansine
timeFrame: Regimen A: predose (0 minutes [min]) and 15-30 min postinfusion on Days (D) 1, 8, 15 of Cycle (C) 1 and D1C4; predose on D1C2. Regimen B: predose and 15-30 min postinfusion on D1C1 and D1C4; predose on D1C2. 1 Cycle=21 days
Other outcomes:
Locations:
city: Meldola
country: Italy
facility: IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
state: Emilia-Romagna
city: Milano
country: Italy
facility: Irccs Ospedale San Raffaele;Oncologia Medica
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Europeo Di Oncologia (IEO); Cure Mediche
state: Lombardia
city: Padova
country: Italy
facility: IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima
state: Veneto
city: Verona
country: Italy
facility: A.O.U.I. VERONA-OSPEDALE POLICLINICO G.B. ROSSI BORGO ROMA;ONCOLOGIA MEDICA-d.U.
state: Veneto
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Ziekenhuis
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC Location VUMC
city: NL -groningen
country: Netherlands
facility: UMCG
city: NL -rotterdam
country: Netherlands
facility: Erasmus MC - Centrum
city: Bratislava
country: Slovakia
facility: Narodny onkologicky ustav
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Barcelona
country: Spain
facility: Hospital Duran i Reynals; Oncologia
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre; Servicio de Oncologia
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: