Clinical trial NCT01211483: Study of Erlotinib With or Without Investigational Drug (U3-1287) in Subjects With Advanced Non-small Cell Lung Cancer
Official title: Randomized, Placebo-controlled, Double-blind Phase 1b/2 Study of U3-1287 (AMG 888) in Combination With Erlotinib in EGFR Treatment Naïve Subjects With Advanced Non-Small Cell Lung Cancer (NSCLC) Who Have Progressed on at Least One Prior Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: NSCLC (Advanced Non-small Cell Lung Cancer)
Keywords: Lung cancer
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2010-09-29
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1b/2 study. In Phase 1b, subjects will know the treatment they are receiving. Subjects will receive Erlotinib + U3-1287. The Phase 1b portion will determine if adding U3-1287 to Erlotinib will be safe in subjects with advanced non-small cell lung cancer who fail prior treatment. In the Phase 2 portion, subjects will be blinded to the treatments they are receiving. Subjects will receive either Erlotinib alone or Erlotinib + U3-1287.

The Phase 2 portion will determine if adding U3-1287 to Erlotinib will be safe and improve survival in subjects with advanced non-small cell lung cancer who failed the first treatment.


Eligibility criteria: Inclusion Criteria:

* ≥ 18 years of age.
* Histologically or cytologically confirmed stage IIIB not amenable to surgery or curative intent or stage IV NSCLC.
* Disease progression or recurrence following treatment after last chemotherapy or chemoradiation regimen (completed within the previous 12 months) documented by radiographic assessment.
* Measurable disease by Response Evaluation Criteria for Solid Tumors v1.1 (RECIST v1.1).
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate bone marrow, renal, and hepatic function.
* Prothrombin time and partial thromboplastin time ≤1.5 x upper limit of normal (ULN).
* Availability of recent (before treatment start) or archival tumor specimens (Phase 2 participants only).
* For female participants, must be postmenopausal, surgically sterile, or must use maximally effective birth control during the period of therapy, and must be willing to use effective contraception up to 6 months after the last dose of study drug and had a negative urine or serum pregnancy test before entry into the study if female participants were of childbearing potential.
* For male participants, must be surgically sterile or willing to use a double barrier contraception method upon enrollment, during the course of the study, and for 6 months following the last investigational drug dose
* Written informed consent.

Exclusion Criteria:

* Left ventricular ejection fraction (LVEF) \< 45%.
* Prior epidermal growth factor receptor (EGFR)-targeted regimen, anti-HER2, anti-HER3, or anti-HER4 therapy.
* More than 2 prior chemotherapy regimens for NSCLC (Phase 2 participants only).
* History of other malignancies, except adequately treated nonmelanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years.
* History of corneal disease.
* History of interstitial lung disease.
* Clinically active brain metastases, defined as untreated symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Participants with treated brain metastases that were no longer symptomatic and required no treatment with steroids could be included in the study if they had recovered from the acute toxic effect of radiotherapy.
* Uncontrolled hypertension (diastolic \> 100 mmHg or systolic \> 140 mmHg).
* Clinically significant electrocardiogram changes that obscured the ability to assess the respiratory rate, pulse rate, QT, QTc, and QRS intervals.
* Ascites or pleural effusion requiring chronic medical intervention.
* Myocardial infarction within 1 year before enrollment, symptomatic congestive heart failure (New York Heart Association \> Class II), unstable angina, or unstable cardiac arrhythmia requiring medication.
* Treatment with anticancer therapy, antibody based therapy, retinoid therapy, or hormonal therapy within 4 weeks before study treatment or treatment with nitrosoureas or mitomycin C within 6 weeks before study drug treatment or treatment with small molecule tyrosine kinase inhibitors (TKIs) within 2 weeks before study drug treatment. Prior and concurrent use of hormone replacement therapy was permitted.
* Therapeutic radiation or major surgery within 4 weeks before study treatment or palliative radiation therapy within 2 weeks before study drug treatment.
* Participated in clinical drug trials within 4 weeks (2 weeks for small molecule TKIs) before study drug treatment. Current participation in other investigational procedures.
* Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
* History of hypersensitivity to any of the study drugs or to any excipients.
* Concurrent use of CYP3A4 inducers or inhibitors.
* Any known pre-existing condition including substance abuse that could interfere with participant's participation in and completion of the protocol.

Primary outcomes:
measure: Progression-Free Survival Following U3-1287 (AMG 888) in Combination With Erlotinib
timeFrame: Time from the randomization date up to the date of first objective documentation of disease progression or death due to any cause (whichever comes first), up to 3 years 2 months
measure: Progression-Free Survival in Participants With High Heregulin-Expressing Tumors Following U3-1287 (AMG 888) in Combination With Erlotinib
timeFrame: Time from the randomization date up to the date of first objective documentation of disease progression or death due to any cause (whichever comes first), up to 3 years 2 months
measure: Progression-Free Survival in Participants With Low Heregulin-Expressing Tumors Following U3-1287 (AMG 888) in Combination With Erlotinib
timeFrame: Time from the randomization date up to the date of first objective documentation of disease progression or death due to any cause (whichever comes first), up to 3 years 2 months
Secondary outcomes:
measure: Overall Survival Following U3-1287 (AMG 888) in Combination With Erlotinib
timeFrame: Time from the randomization date up to the date of death due to any cause, up to 3 years 2 months
measure: Objective Response Following U3-1287 (AMG 888) in Combination With Erlotinib
timeFrame: Time from date of randomization up to date of first documentation of objective response of either CR or PR (whichever comes first), up to 3 years 2 months
measure: Time to Objective Response Following U3-1287 (AMG 888) in Combination With Erlotinib
timeFrame: Time from date of randomization up to date of first documentation of objective response of either CR or PR (whichever comes first), up to 3 years 2 months
measure: Duration of Stable Disease Following U3-1287 (AMG 888) in Combination With Erlotinib
timeFrame: For participants whose best response is SD as the time from date of first documentation of stable disease up to the date of first documentation of progressive disease, up to 3 years 2 months
measure: Time to Disease Progression Following U3-1287 (AMG 888) in Combination With Erlotinib
timeFrame: Time from date of randomization up to the date of first objective documentation of disease progression, up to 3 years 2 months
measure: Pharmacokinetic Parameter of Cycle 3 Patritumab Area Under the Concentration-time Curve Over the Dosing Interval 0 to τ (AUC) Following U3-1287 (AMG 888) in Combination With Erlotinib
timeFrame: Cycle 1: predose, end of infusion (EOI), 3 hour (h) postdose; Cycle 2: predose; Cycle 3: predose, EOI, 3 h, 6h, 24 h, 72 h, 168 h, 336 h; Cycle 4, Cycle 5, Cycle 7, and Cycle 9: predose (each cycle is 21 days)
measure: Pharmacokinetic Parameter of Cycle 3 Patritumab Concentration End of Infusion (CEOI) and Minimum (Trough) Concentration (Cmin) Following U3-1287 (AMG 888) in Combination With Erlotinib
timeFrame: Cycle 1: predose, end of infusion (EOI), 3 hour (h) postdose; Cycle 2: predose; Cycle 3: predose, EOI, 3 h, 6h, 24 h, 72 h, 168 h, 336 h; Cycle 4, Cycle 5, Cycle 7, and Cycle 9: predose (each cycle is 21 days)
measure: Erlotinib Concentrations at Cycle 3 Day 1 Following U3-1287 (AMG 888) in Combination With Erlotinib
timeFrame: Cycle 3, Day 1: predose, 1 h, 2 h, 3 h, 6h, 24 h postdose (each cycle is 21 days)
measure: Pharmacokinetic Parameter of Erlotinib Trough (Cmin) Concentrations From Participants Receiving 150 mg Erlotinib Following U3-1287 (AMG 888) in Combination With Erlotinib
timeFrame: Cycle 1: predose, end of infusion (EOI), 3 hour (h) postdose; Cycle 2: predose; Cycle 3: predose, EOI, 3 h, 6h, 24 h, 72 h, 168 h, 336 h; Cycle 5, Cycle 7, and Cycle 9: predose (each cycle is 21 days)
measure: Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib
timeFrame: From the date of signing the informed consent form up to 53 days after the last dose of patritumab/placebo or up to 30 days after the last dose of erlotinib if patritumab/placebo was discontinued earlier, up to 3 years 2 months
Other outcomes:
Locations:
city: Glendale
country: United States
state: Arizona
city: Scottsdale
country: United States
facility: TRM - Oncology Research Associates, PLLC, d/b/a Pinnacle Oncology Hematology
state: Arizona
city: Anaheim
country: United States
state: California
city: Encinitas
country: United States
state: California
city: La Verne
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Orlando
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Joliet
country: United States
state: Illinois
city: Evansville
country: United States
state: Indiana
city: Baton Rouge
country: United States
state: Louisiana
city: Detroit
country: United States
state: Michigan
city: Bronx
country: United States
state: New York
city: York
country: United States
state: Pennsylvania
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Gent
country: Belgium
city: Liege
country: Belgium
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Essen
country: Germany
city: Frankfurt am Main
country: Germany
city: Freiburg
country: Germany
city: Gauting
country: Germany
city: Halle
country: Germany
city: Hamburg
country: Germany
city: Herne
country: Germany
city: Lowenstein
country: Germany
city: Mainz
country: Germany
city: Tubingen
country: Germany
city: Budapest
country: Hungary
city: Pecs
country: Hungary
city: Petah Tikva
country: Israel
city: Tel Aviv
country: Israel
city: Tel HaShomer
country: Israel
city: Lido di Camaiore
country: Italy
city: Piacenza
country: Italy
city: Pisa
country: Italy
city: Reggio Emilia
country: Italy
city: Kaunas
country: Lithuania
city: Vilnius
country: Lithuania
city: Suceava
country: Romania
city: Târgu-Mureş
country: Romania
city: Golnik
country: Slovenia
city: Dnipropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Ivano-Frankivsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Sumy
country: Ukraine
city: Uzhgorod
country: Ukraine
city: London
country: United Kingdom
city: Wirral
country: United Kingdom
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: