A Study to Determine Best Tumor Response With Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2 (HER2) Overexpressing Solid Tumors

NCT ID: NCT02999672

Last Updated: 2019-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-23
• Study Completion Date: 2018-04-10

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.

Conditions

Bladder Cancer; Pancreas Cancer; Cholangiocellular Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1 (UBC)

First six participants with locally advanced (unresectable and not treatable with curative intent) or metastatic UBC will initially receive Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC will assess the safety among the first six participants and decide whether dose will be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).

Group Type: EXPERIMENTAL

Trastuzumab Emtansine

Intervention Type: DRUG

Trastuzumab emtansine will be administered as Regimen A (2.4 mg/kg qw via IV infusion) or Regimen B (3.6 mg/kg q3w via IV infusion) until unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurs first.

Cohort 2 (Pancreatic cancer/cholangiocarcinoma)

First six participants with metastatic pancreatic cancer/cholangiocarcinoma will receive Regimen A (trastuzumab emtansine at a dose of 2.4 mg/kg qw). An iDMC will assess the safety among the first six participants and decide whether dose will be switched to Regimen B (trastuzumab emtansine at a dose of 3.6 mg/kg q3w).

Group Type: EXPERIMENTAL

Trastuzumab Emtansine

Intervention Type: DRUG

Trastuzumab emtansine will be administered as Regimen A (2.4 mg/kg qw via IV infusion) or Regimen B (3.6 mg/kg q3w via IV infusion) until unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurs first.

Interventions

Trastuzumab Emtansine

Trastuzumab emtansine will be administered as Regimen A (2.4 mg/kg qw via IV infusion) or Regimen B (3.6 mg/kg q3w via IV infusion) until unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurs first.

Intervention Type: DRUG

Other Intervention Names

Kadcyla

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica

Meldola, Emilia-Romagna, Italy

Irccs Ospedale San Raffaele;Oncologia Medica

Milan, Lombardy, Italy

Irccs Istituto Europeo Di Oncologia (IEO); Cure Mediche

Milan, Lombardy, Italy

IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima

Padua, Veneto, Italy

A.O.U.I. VERONA-OSPEDALE POLICLINICO G.B. ROSSI BORGO ROMA;ONCOLOGIA MEDICA-d.U.

Verona, Veneto, Italy

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, , Netherlands

Amsterdam UMC Location VUMC

Amsterdam, , Netherlands

UMCG

NL -groningen, , Netherlands

Erasmus MC - Centrum

NL -rotterdam, , Netherlands

Narodny onkologicky ustav

Bratislava, , Slovakia

Complejo Hospitalario de Navarra

Pamplona, Navarre, Spain

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, , Spain

Hospital Duran i Reynals; Oncologia

Barcelona, , Spain

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, , Spain

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, , Spain

Hospital Regional Universitario Carlos Haya; Servicio de Oncologia

Málaga, , Spain

Countries

Italy; Netherlands; Slovakia; Spain

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2015-001377-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MO29694

Identifier Type: -

Identifier Source: org_study_id