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

NCT02999672 | Completed Phase 2 Results DMC

• 2 other identifiers: MO296942015-001377-40
• Study Type: interventional
• Target: 20
• Locations: 4 countries
• Sites: 16

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

Outcome Measures

Primary Outcomes (1)

• Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).

  BOR was defined as having best objective response as complete response (CR) or partial response (PR), as assessed by investigator and confirmed at least 28 days after initial response, according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must decrease to normal (short axis less than \[\<\] 10 millimeter \[mm\]). PR was defined as a 30% decrease in the sum of the diameters of the target lesions taking as a reference the baseline sum diameter. Percentage of participants with best overall response of CR or PR are reported.

  Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)

Secondary Outcomes (5)

• Progression-Free Survival (PFS)

  Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)

• Overall Survival (OS)

  Baseline up to PD/recurrence or death, whichever occurs first (up to approximately 18 months)

• Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)

  Baseline up to approximately 18 months

• Percentage of Participants With Drug-induced Liver Injury Meeting Hy's Law Criteria

  Baseline up to approximately 18 months

• Plasma/Serum Concentrations of Trastuzumab Emtansine

  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

Study Arms (2)

Cohort 1 (UBC)

EXPERIMENTAL

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).

Drug: Trastuzumab Emtansine

Cohort 2 (Pancreatic cancer/cholangiocarcinoma)

EXPERIMENTAL

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).

Drug: Trastuzumab Emtansine

Interventions

Trastuzumab Emtansine 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.

Also known as: Kadcyla

Cohort 1 (UBC); Cohort 2 (Pancreatic cancer/cholangiocarcinoma)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (16)

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

Meldola, Emilia-Romagna, 47014, Italy

Location

Irccs Ospedale San Raffaele;Oncologia Medica

Milan, Lombardy, 20132, Italy

Location

Irccs Istituto Europeo Di Oncologia (IEO); Cure Mediche

Milan, Lombardy, 20141, Italy

Location

IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima

Padua, Veneto, 35128, Italy

Location

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

Verona, Veneto, 37134, Italy

Location

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

Amsterdam UMC Location VUMC

Amsterdam, 1081 HV, Netherlands

Location

UMCG

NL -groningen, 9700 RB, Netherlands

Location

Erasmus MC - Centrum

NL -rotterdam, 3000 CA, Netherlands

Location

Narodny onkologicky ustav

Bratislava, 833 10, Slovakia

Location

Complejo Hospitalario de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, 08035, Spain

Location

Hospital Duran i Reynals; Oncologia

Barcelona, 08907, Spain

Location

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, 28041, Spain

Location

Hospital Regional Universitario Carlos Haya; Servicio de Oncologia

Málaga, 29010, Spain

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Pancreatic Neoplasms; Cholangiocarcinoma

Interventions

Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The results represent the data up to primary completion date (10 April 2018). However, due to the early termination, the study was unable to fully address its primary and secondary objectives.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

1-800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2016
• First Posted: December 21, 2016
• Study Start: December 23, 2016
• Primary Completion: April 10, 2018
• Study Completion: April 10, 2018
• Last Updated: August 28, 2019
• Results First Posted: August 28, 2019

Record last verified: 2019-07

Locations

IT (5); ES (6); SL (1); NL (4)