Clinical trial NCT02134015: Study of Patritumab in Combination With Erlotinib in Subjects With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC). (HER3-Lung)
Official title: Phase 3, Randomized, Placebo-Controlled, Double-Blind, Multi-Center, Two-Part Study of Patritumab (U3-1287) In Combination With Erlotinib in EGFR Wild-type Subjects With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) Who Have Progressed on at Least One Prior Systemic Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Lung Cancer
Non-small Cell Lung Cancer
Keywords: Carcinoma
Non-Small-Cell Lung
Lung Neoplasms
Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Erlotinib
Therapeutic Uses
Pharmacologic Actions
Molecular Mechanisms of Pharmacological Action
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2014-05-08
Enrollment: 145
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 1. Part A: Subjects will receive Patritumab or placebo with erlotinib. Progression-free survival will be the primary outcome. Subjects will need to have Epidermal Growth Factor Receptor (EGFR) wild-type, locally advance or metastatic NSCLC and have their cancer progressed after at least one prior systemic anti-cancer therapy, available recent or archival tumor specimen and may not have had previous EGFR-targeted regimen, anti-HER2 (Human Epidermal Growth Factor Receptor 2), anti-HER3, or anti-HER4 therapy. Subjects may have high heregulin or low heregulin.
2. Part B: Subjects will receive Patritumab or placebo with erlotinib. Overall survival will be the primary outcome. Subjects will need to have EGFR wild-type, locally advance or metastatic NSCLC and have their cancer progressed after at least one prior systemic anti-cancer therapy, available recent or archival tumor specimen and may not have had previous EGFR-targeted regimen, anti-HER2, anti-HER3, or anti-HER4 therapy. Only subjects with high heregulin will be enrolled.


Eligibility criteria: Inclusion Criteria:

1. Must be greater or equal to 20 years of age
2. Must have cytologically or histologically confirmed NSCLC with either:

   * Metastatic disease (Stage IV) OR
   * Stage IIIB disease not amenable to surgery or curative intent.

   Note: It is permissible to use either AJCC Version 6.0 or the AJCC Version 7.0 staging system. For sites that use AJCC Version 7.0, T4M0 patients with other ipsilateral nodules and N0-N2 are still eligible.
3. If tumor histology is adenocarcinoma, must have wild-type EGFR genotype as assessed by a validated assay that includes exon 19 deletion and exon 21 (L858R) substitution.
4. Must have received one or two prior lines of systemic chemotherapy for advanced or metastatic disease, one of which must be a platinum-doublet therapy.
5. Must have disease progression or recurrence documented by radiographic assessment following treatment after last chemotherapy or chemoradiation regimen (completed within the previous 12 months).
6. Must have available recent (before treatment start) or archival tumor specimen.
7. Must have measurable disease for Part A, measurable disease or non-measurable disease for Part B
8. Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
9. Must have adequate hematological function
10. Must have adequate renal function
11. Must have adequate hepatic function
12. Agreement to use effective contraception while on treatment and for at least 6 months after end of treatment
13. Must have provided informed consent for study participation.

Exclusion Criteria:

1. Lung adenocarcinoma with an Anaplastic Lymphoma Kinase (ALK) gene rearrangement
2. Left ventricular ejection fraction (LVEF) less than 45%
3. Prior EGFR-targeted regimen, anti-HER2, anti-HER3, or anti-HER4 therapy
4. History of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for greater or equal to 5 years
5. History of corneal disease
6. History of interstitial lung disease (ILD)
7. Clinically active brain metastases
8. Uncontrolled hypertension
9. Clinically significant ECG changes
10. Clinically significant (in the opinion of the Investigator) ascites or pleural effusion requiring chronic medical intervention
11. Myocardial infarction within 1 year before enrollment, symptomatic congestive heart failure, unstable angina, or unstable cardiac arrhythmia requiring medication
12. Treatment with anticancer therapy, antibody-based therapy, retinoid therapy, or hormonal therapy within 4 weeks before study drug treatment
13. Therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment; or palliative radiation within 2 weeks before study drug treatment
14. Participation in clinical drug trials within 4 weeks
15. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
16. History of hypersensitivity to any of the study drugs or to any excipients.

Primary outcomes:
measure: Part A: Progression Free Survival (PFS) in Heregulin-high Participants
timeFrame: by trial termination (at 20 months)
measure: Part A: Progression Free Survival (PFS) in Heregulin-low Participants
timeFrame: by trial termination (at 20 months)
measure: Part B: Overall Survival
timeFrame: 4 years
Secondary outcomes:
measure: Part A: Overall Survival in HRG High Participants
timeFrame: by trial termination (at 20 months)
measure: Part A: Key Secondary Efficacy Endpoint: Overall Survival in HRG Low Participants
timeFrame: by trial termination (at 20 months)
measure: Part B: Key Secondary Efficacy Endpoint: PFS, TTD
timeFrame: 4 years
measure: Part A: Objective Response Rate (ORR) in HRG High Participants
timeFrame: by trial termination (at 20 months)
measure: Part A: Objective Response Rate (ORR) in HRG Low Participants
timeFrame: by trial termination (at 20 months)
Other outcomes:
Locations:
city: Glendale
country: United States
state: Arizona
city: Duarte
country: United States
state: California
city: La Verne
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Port Saint Lucie
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Maywood
country: United States
state: Illinois
city: Goshen
country: United States
state: Indiana
city: Louisville
country: United States
state: Kentucky
city: Grand Rapids
country: United States
state: Michigan
city: Saint Cloud
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Columbus
country: United States
state: Ohio
city: Bend
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Redmond
country: United States
state: Oregon
city: Chattanooga
country: United States
state: Tennessee
city: Knoxville
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Arlington
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Brasschaat
country: Belgium
state: Antwerpen
city: Bruxelles
country: Belgium
state: Brussels
city: Charleroi
country: Belgium
state: Hainaut
city: Charleroi
country: Belgium
city: Gent
country: Belgium
city: Liege
country: Belgium
city: Yvoir
country: Belgium
city: Hamilton
country: Canada
state: Ontario
city: Kingston
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Levis
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Ostava-Poruba
country: Czechia
city: Ostrava-Poruba
country: Czechia
city: Esslingen am Neckar
country: Germany
state: Baden-Wurttemberg
city: Gerlingen
country: Germany
state: Baden-Wurttemberg
city: Heidelberg
country: Germany
state: Baden-Württemberg
city: Ulm
country: Germany
state: Baden-Württemberg
city: Villingen-Schwenningen
country: Germany
state: Baden-Württemberg
city: Gauting
country: Germany
state: Bayern
city: Muenchen
country: Germany
state: Bayern
city: Frankfurt am Main
country: Germany
state: Hessen
city: Immenhausen
country: Germany
state: Hessen
city: Koln
country: Germany
state: Nordrhein-Westfalen
city: Rheine
country: Germany
state: Nordrhein-Westfalen
city: Mainz
country: Germany
state: Rheinland-Pfalz
city: Halle
country: Germany
state: Sachsen-Anhalt
city: Grosshansdorf
country: Germany
state: Schleswig-Holstein
city: Gießen
country: Germany
city: Szekesfehervar
country: Hungary
state: Fejer
city: Gyor
country: Hungary
state: Gyor-Moson-Sopron
city: Szolnok
country: Hungary
state: Jasz-Nagykun-Szolnok
city: Tatabanya
country: Hungary
city: Meldola
country: Italy
state: Forli
city: Sora
country: Italy
state: Frosinone
city: Lecco
country: Italy
state: Lombardia
city: Benevento
country: Italy
city: Bologna
country: Italy
city: Cremona
country: Italy
city: Faenza
country: Italy
city: Genova
country: Italy
city: Milano
country: Italy
city: Napoli
country: Italy
city: Perugia
country: Italy
city: Ravenna
country: Italy
city: Rimini
country: Italy
city: Roma
country: Italy
city: Rozzano
country: Italy
city: Torun
country: Poland
state: Kujawsko-pomorskie
city: Otwock
country: Poland
state: Mazowieckie
city: Gdansk
country: Poland
state: Pomorskie
city: Szczecin
country: Poland
state: Zachodniopomorskie
city: Krakow
country: Poland
city: Prabuty
country: Poland
city: Warszawa
country: Poland
city: La Coruna
country: Spain
state: A Coruña
city: Sevilla
country: Spain
state: Andalucia
city: Valencia
country: Spain
state: Valenciana, Comunidad
city: Alicante
country: Spain
city: Barcelona (2)
country: Spain
city: Barcelona (3)
country: Spain
city: Barcelona (4)
country: Spain
city: Barcelona (5)
country: Spain
city: Barcelona (6)
country: Spain
city: Barcelona
country: Spain
city: Burgos (2)
country: Spain
city: Burgos
country: Spain
city: Madrid (2)
country: Spain
city: Madrid (3)
country: Spain
city: Madrid (4)
country: Spain
city: Madrid
country: Spain
city: Manresa (2)
country: Spain
city: Manresa
country: Spain
city: Palma de Mallorca
country: Spain
city: Valencia
country: Spain
city: Zaragoza (2)
country: Spain
city: Zaragoza
country: Spain
city: Stevenage
country: United Kingdom
state: Hertfordshire
city: London (2)
country: United Kingdom
city: London (3)
country: United Kingdom
city: London
country: United Kingdom
city: Northwood
country: United Kingdom
city: Rickmansworth
country: United Kingdom
city: Southampton
country: United Kingdom
city: Wirral
country: United Kingdom
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: