Clinical trial NCT02318368: A Phase 2, Study of Ficlatuzumab Plus Erlotinib vs. Placebo Plus Erlotinib in Subjects With Previously Untreated Metastatic, EGFR-mutated NSCLC and BDX004 Positive Label
Official title: A Phase 2, Multicenter, Randomized, Double-blind Study of Ficlatuzumab Plus Erlotinib Versus Placebo Plus Erlotinib in Subjects Who Have Previously Untreated Metastatic, EGFR-mutated Non-small Cell Lung Cancer (NSCLC) and BDX004 Positive Label
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Lead sponsor: AVEO Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Biodesix, Inc.
First posted: 2014-12-17
Enrollment: 10
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: Phase 2 multicenter, controlled, randomized, double-blind study to evaluate the efficacy and safety of ficlatuzumab versus placebo when administered with erlotinib in subjects with previously untreated metastatic EGFR-mutated NSCLC and BDX004 Positive Label.

Detailed description: This is a Phase 2 multicenter, controlled, randomized, double-blind study to evaluate the efficacy and safety of ficlatuzumab versus placebo when administered with erlotinib in subjects with previously untreated metastatic EGFR-mutated NSCLC and BDX004 Positive Label.

Prior to screening, subjects will have tested positive for a sensitizing EGFR mutation to determine eligibility for treatment with erlotinib. During screening, subject serum samples will be tested using the investigational companion diagnostic (BDX004) test. Only those subjects who have a BDX004 Positive Label will be enrolled. Subject randomization will be stratified by EGFR mutation type and smoking status (ever versus never smokers). Subjects will be designated as never smokers if they have smoked less than 100 cigarettes in their lifetime. Radiographic tumor assessment, to include CT or MRI of chest and abdomen, will be performed every 4 weeks for the first 8 cycles, and every 8 weeks thereafter, using the same imaging modality per subject. Safety assessments will be performed on an ongoing basis.

Eligibility criteria: Inclusion Criteria

* Histologically and/or cytologically confirmed primary diagnosis of Stage IV NSCLC (according to American Joint Committee on Cancer \[AJCC\] 7th edition lung cancer staging criteria).
* Measurable disease according to RECIST v.1.1.
* An EGFR exon 19 deletion and/or an exon 21 (L858R) substitution mutation.
* BDX004 Positive Label.
* Have received no prior systemic chemotherapy, immunotherapy, targeted therapy, or biologic therapy for metastatic NSCLC. Subjects may have previously been treated with postoperative adjuvant chemotherapy for early stage lung cancer or chemo radiotherapy for locally advanced disease provided this was completed at least 6 months prior to enrollment. No prior EGFR TKI therapy is allowed for any stage of NSCLC.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Exclusion Criteria
* History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent or erlotinib.
* History of known brain metastases.
* Prior treatment with any other investigational drug or biologic agent within 5 half lives prior to randomization, or any investigational device within 2 weeks prior to randomization.
* Any unresolved toxicity from previous radiation therapy.
* Significant cardiovascular disease, including:

  * Echocardiogram (ECHO) or multiple gated acquisition (MUGA) showing left ventricular ejection fraction of less than 55%.
  * Cardiac failure New York Heart Association class III or IV.
  * Myocardial infarction, severe or unstable angina within 6 months prior to randomization.
  * History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation).
  * Significant thrombotic or embolic events within 3 months prior to randomization (significant thrombotic or embolic events include but are not limited to stroke or transient ischemic attack).
  * Any uncontrolled or severe cardiovascular disease.
* History of prior malignancy within 3 years prior to randomization (except for adequately treated non-melanoma skin cancer, carcinoma in situ of the breast or cervix, superficial bladder cancer, or early stage prostate cancer, without evidence of recurrence).
* Radiographic evidence of interstitial lung disease.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Approximately 24 months
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Approximately 24 months
Other outcomes:
Locations:
city: Fresno
country: United States
facility: UCSF Fresno
state: California
city: Redondo Beach
country: United States
facility: Torrance Memorial Medical Center
state: California
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital Lynn Cancer Institute
state: Florida
city: Deerfield Beach
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center Deerfield Beach
state: Florida
city: Honolulu
country: United States
facility: Kaiser Permanente Hawaii
state: Hawaii
city: Lafayette
country: United States
facility: Cancer Center of Acadiana
state: Louisiana
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Paramus
country: United States
facility: Valley Medical Group
state: New Jersey
city: Jamaica
country: United States
facility: Queens Hospital Cancer Center
state: New York
city: Canton
country: United States
facility: Aultman Hospital
state: Ohio
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Cancer Center Cancer
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Coffs Harbour
country: Australia
facility: North Coast Cancer Institute
state: New South Wales
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Douglas
country: Australia
facility: Townsville Hospital
state: Queensland
city: Southport
country: Australia
facility: Icon Cancer Care
state: Queensland
city: Wolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Box Hill
country: Australia
facility: Eastern Health
state: Victoria
city: Frankston
country: Australia
facility: Frankston Hospital
state: Victoria
city: Wendouree
country: Australia
facility: Ballarat Oncology and Haematology
state: Victoria
city: Tuen Mun
country: Hong Kong
facility: Tuen Mun Hospital
state: N.T
city: Pok Fu Lam
country: Hong Kong
facility: Queen Mary Hospital
city: Benevento
country: Italy
facility: AO G.Rummo
city: Bologna
country: Italy
facility: Policlinico S.Orsola Malpighi
city: Cremona
country: Italy
facility: Istituti Ospitalieri di Cremona - Oncologia
city: Lucca
country: Italy
facility: U.O.C. Oncologia
city: Milano
country: Italy
facility: IRCCS Ospedale S.Raffaele
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri
city: Rozzano MI
country: Italy
facility: IRCCS Istituto Clinico Humanitas
city: Treviglio BG
country: Italy
facility: Ospedale Treviglio-Caravaggio
city: Guro-gu
country: Korea, Republic of
facility: Korea University Guro Hospital
state: Seoul
city: Chungcheongbuk-do
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Jeonnam
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei Uni
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Central Singapore
country: Singapore
facility: John Hopkins Singapore International Medical Center
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Taichung
country: Taiwan
facility: Chung Shan Medical University
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University
city: Taoyuan City
country: Taiwan
facility: Chang Gung Medical Foundation
Study officials:
affiliation: AVEO Pharmaceuticals, Inc.
name: Michael N Needle, MD
role: STUDY_DIRECTOR
References: