Clinical trial NCT02186301: TIGER-1: Safety and Efficacy Study of Rociletinib (CO-1686) or Erlotinib in Patients With EGFR-mutant/Metastatic NSCLC Who Have Not Had Any Previous EGFR Directed Therapy
Official title: TIGER 1: A Randomized, Open-Label, Phase 2/3 Study of CO-1686 or Erlotinib as First-Line Treatment of Patients With EGFR-Mutant Advanced/Metastatic NSCLC
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Non-Small Cell Lung Cancer
Keywords: cancer
metastatic
locally advanced
lung
non-small cell lung cancer
NSCLC
epidermal growth factor receptor
EGFR
T790M
CO-1686
unresectable
recurrent
EGFR-directed therapy
irreversible EGFR inhibitor
TIGER
rociletinib
Lead sponsor: Clovis Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2014-07-10
Enrollment: 100
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: The purpose of this study is to compare the safety and anti-tumor effect of rociletinib with erlotinib in patients whose tumors have specific EGFR mutations and who have not previously received any treatment for advanced/metastatic EGFR mutated NSCLC. This study is a 'Randomized' Study. This means that upon entering the study, patients will be randomly assigned to be dosed with either rociletinib twice a day or erlotinib once a day. Patients will continue to take either rociletinib or erlotinib until it is no longer beneficial.

Detailed description: This is a randomized, Phase 2/3 study of rociletinib versus erlotinib as a first-line treatment for patients with EGFR-mutant advanced/metastatic NSCLC whose tumors have EGFR-activating mutations. The study will consist of Phase 2 and Phase 3 parts which will use the same enrollment criteria and treatment assignment principles. Patients will be randomized 1:1 to erlotinib or rociletinib. The Phase 2 part is an open-label study. In the Phase 3 part, the sponsor will be blinded to the efficacy and safety results. The study will consist of a screening phase to establish study eligibility (including tumor genotype) and document baseline measurements, a treatment phase, in which patients will receive either rociletinib BID (twice a day) or erlotinib QD (once daily) to ascertain safety and efficacy until protocol-defined disease progression, and a follow-up phase, to monitor survival status and subsequent NSCLC cancer therapy. In the Phase 2 part only, patients initially randomized to erlotinib may be eligible to participate in an optional crossover phase to receive rociletinib if they demonstrate the T790M resistance mutation after radiographic progression on erlotinib treatment among other eligibility requirements. Patients eligible for this study must have EGFR-mutated NSCLC who have not been treated with an EGFR-directed therapy.Treatment with rociletinib or erlotinib is continuous. Each 28 day period of treatment will represent one cycle, with dosing initiated on Cycle 1 Day 1 (C1 D1).

Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically confirmed metastatic or unresectable locally advanced/metastatic NSCLC
2. Documented evidence of a tumor with activating EGFR mutations by local testing. Patients with exon 20 insertions are not eligible with the exception of patients with documented evidence of the exon 20 insertion A763_Y764insFQEA in the EGFR gene
3. Have undergone a biopsy or surgical resection of either primary or metastatic tumor tissue within 60 days of the first day of study treatment, C1D1, and have tissue available to send to sponsor laboratories or are able to undergo a biopsy during screening and provide tissue to sponsor laboratories
4. Measureable disease according to RECIST Version 1.1
5. Life expectancy of at least 3 months
6. ECOG (Eastern Cooperative Oncology Group) performance status of 0 to 1
7. Minimum age 18 years (in certain territories, the minimum age requirement may be higher (e.g. 20 years in Japan and Taiwan)
8. Adequate hematological and biological function, confirmed by defined laboratory values
9. Written consent on an IRB/IEC-approved Informed Consent Form (ICF) prior to any study-specific evaluation

Exclusion Criteria:

1. Documented evidence of an exon 20 insertion activating mutation other than A763_Y764insFQEA in the EGFR gene
2. Prior treatment with cytotoxic chemotherapy for advanced NSCLC; neoadjuvant/adjuvant chemotherapy is permitted if at least 6 months has elapsed between the end of chemotherapy and randomization
3. Active second malignancy; i.e., patient known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment
4. Patients with a history of malignancy that has been completely treated, and currently with no evidence of that cancer, are permitted to enroll in the trial provided all chemotherapy was completed \> 6 months prior and/or bone marrow transplant \> 2 years prior to first day of study treatment
5. Known pre-existing interstitial lung disease
6. Brain metastases
7. Treatment with prohibited medications less than or equal to 14 days prior to first day of study treatment
8. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval if that treatment cannot be either discontinued or switched to a different medication prior to administration of study drug
9. Prior treatment with EGFR TKIs (e.g. erlotinib, gefitinib, neratinib, afatinib, AZD9291, or dacomitinib), rociletinib or other drugs that target mutant EGFR
10. Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTCF) \> 450 ms
11. Inability to measure QT interval on ECG
12. Personal or family history of long QT syndrome
13. Implantable pacemaker or implantable cardioverter defibrillator
14. Resting bradycardia \< 55 beats/min
15. Non-study related surgical procedures less than or equal to 7 days prior to administration of study drug. In all cases, the patient must be sufficiently recovered and stable before treatment administration.
16. Females who are pregnant or breastfeeding
17. Refusal to use adequate contraception for fertile patients (females and males) for 12 weeks after the last dose of rociletinib and 2 weeks after the last dose of erlotinib
18. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study
19. Any other reason the investigator considers the patient should not participate in the study

Primary outcomes:
measure: Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)
timeFrame: Cycle 1 Day 1 to End of Treatment, up to approximately 35 months
Secondary outcomes:
measure: Confirmed Response Rate
timeFrame: Cycle 1 Day 1 to End of Treatment, up to approximately 35 months.
measure: Duration of Response
timeFrame: Cycle 1 Day 1 to End of Treatment, up to approximately 35 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Burbank
country: United States
facility: East Valley Hematology and Oncology Medical Group, Inc.
state: California
city: Duarte
country: United States
facility: City of Hope
state: California
city: Fountain Valley
country: United States
facility: Compassionate Cancer Care Medical Group, Inc.
state: California
city: Fullerton
country: United States
facility: St. Joseph Heritage Healthcare
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California, Norris Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: Sutter Medical Group
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Santa Barbara
country: United States
facility: Sansum Clinic
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation
state: California
city: Santa Monica
country: United States
facility: UCLA Medical Center
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Fleming Island
country: United States
facility: Cancer Specialists of North Florida
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists and Research Institute
state: Florida
city: Miami
country: United States
facility: Advanced Medical Specialties
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Baltimore
country: United States
facility: Harry and Jeanette Weinberg Cancer Institute at Franklin Square
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed Army Institute of Research
state: Maryland
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Omaha
country: United States
facility: Oncology Hematology West PC
state: Nebraska
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: East Brunswick
country: United States
facility: Regional Cancer Care Associates, LLC
state: New Jersey
city: Morristown
country: United States
facility: Regional Cancer Care Associates
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center
state: South Carolina
city: Chattanooga
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology, PA
state: Texas
city: Beaumont
country: United States
facility: Texas Oncology-Beaumont
state: Texas
city: Bedford
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas - MD Anderson Cancer Center
state: Texas
city: Plano
country: United States
facility: Texas Oncology-Plano East
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital, North Star Lodge
state: Washington
city: Gauting
country: Germany
facility: Asklepios Fachkliniken München-Gauting
state: Bayern
city: Oldenburg
country: Germany
facility: Pius Hospital Oldenburg
state: Niedersachsen
city: Köln
country: Germany
facility: Universitätsklinikum Köln
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: Katholisches Klinikum Mainz, Sankt Hildegardis-Krankenhaus
state: Rheinland-Pfalz
city: Berlin
country: Germany
facility: Evangelische Lungenklinik Berlin
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
state: New Territories
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Livorno
country: Italy
facility: Ospedale Civile di Livorno
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea Saint Vincent's Hospital
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital Linkou
Study officials:
References: