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

Non-small Cell Lung Cancer Clinical Trial

— FOCAL  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02318368
• Other study ID #: AV-299-14-206
• Status: Terminated
• Phase: Phase 2
• Start date: November 2014
• Est. completion date: January 2017

Study information

• Verified date: October 2020
• Source: AVEO Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Ficlatuzumab

• Erlotinib

• placebo

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
AVEO Pharmaceuticals, Inc.	Biodesix, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Hong Kong,  Italy,  Korea, Republic of,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	Progression Free Survival is defined as the time from the date of randomization to the date of the first objective documentation of radiographic disease progression or death due to any cause, whichever occurs first.	Approximately 24 months
Secondary	Number of Participants With Adverse Events	To evaluate Safety and tolerability of ficlatuzumab plus erlotinib versus placebo plus erlotinib in subjects who have previously untreated metastatic EGFR-mutated NSCLC and a BDX004 Positive Label.	Approximately 24 months