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

Phase 2

Terminated

Conditions: Non-Small Cell Lung Cancer

Interventions: Drug: Erlotinib Mono-Therapy
Drug: Rociletinib Mono-Therapy

Registration Number: NCT02186301

Lead Sponsor: Clovis Oncology, Inc.

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).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 100

Inclusion Criteria

Histologically or cytologically confirmed metastatic or unresectable locally advanced/metastatic NSCLC
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
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
Measureable disease according to RECIST Version 1.1
Life expectancy of at least 3 months
ECOG (Eastern Cooperative Oncology Group) performance status of 0 to 1
Minimum age 18 years (in certain territories, the minimum age requirement may be higher (e.g. 20 years in Japan and Taiwan)
Adequate hematological and biological function, confirmed by defined laboratory values
Written consent on an IRB/IEC-approved Informed Consent Form (ICF) prior to any study-specific evaluation

Exclusion Criteria

Documented evidence of an exon 20 insertion activating mutation other than A763_Y764insFQEA in the EGFR gene
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
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
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
Known pre-existing interstitial lung disease
Brain metastases
Treatment with prohibited medications less than or equal to 14 days prior to first day of study treatment
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
Prior treatment with EGFR TKIs (e.g. erlotinib, gefitinib, neratinib, afatinib, AZD9291, or dacomitinib), rociletinib or other drugs that target mutant EGFR
Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTCF) > 450 ms
Inability to measure QT interval on ECG
Personal or family history of long QT syndrome
Implantable pacemaker or implantable cardioverter defibrillator
Resting bradycardia < 55 beats/min
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.
Females who are pregnant or breastfeeding
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
Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study
Any other reason the investigator considers the patient should not participate in the study

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Erlotinib Mono-Therapy	Erlotinib Mono-Therapy	-
Rociletinib Mono-Therapy	Rociletinib Mono-Therapy	-

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)	Cycle 1 Day 1 to End of Treatment, up to approximately 35 months	To compare the antitumor efficacy of oral single-agent rociletinib with that of erlotinib as measured by progression-free survival (PFS), when administered as a first-line targeted treatment to patients with EGFR-mutated, advanced NSCLC.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions is also considered progression.

Secondary Outcome Measures

Name	Time	Method
Confirmed Response Rate	Cycle 1 Day 1 to End of Treatment, up to approximately 35 months.	Proportion of patients with a best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression or recurrence. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR),at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Overall Response (OR),is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment was dependent on the achievement of both measurement and confirmation criteria.
Duration of Response	Cycle 1 Day 1 to End of Treatment, up to approximately 35 months	Duration of Response in Patients with Confirmed Response per Investigator

Trial Locations

Locations (73): UCLA Medical Center
🇺🇸
Santa Monica, California, United States
Florida Cancer Specialists and Research Institute
🇺🇸
Fort Myers, Florida, United States
Comprehensive Cancer Centers of Nevada
🇺🇸
Henderson, Nevada, United States
Thomas Jefferson University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
Virginia Cancer Specialists, PC
🇺🇸
Fairfax, Virginia, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
University Hospitals Case Medical Center
🇺🇸
Cleveland, Ohio, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
University of California San Francisco
🇺🇸
San Francisco, California, United States
Advanced Medical Specialties
🇺🇸
Miami, Florida, United States
University of Cincinnati Medical Center
🇺🇸
Cincinnati, Ohio, United States
Houston Methodist Cancer Center
🇺🇸
Houston, Texas, United States
Tennessee Oncology, PLLC
🇺🇸
Nashville, Tennessee, United States
USC/Norris Comprehensive Cancer Center
🇺🇸
Nashville, Tennessee, United States
The University of Texas - MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
University of Washington
🇺🇸
Seattle, Washington, United States
City of Hope
🇺🇸
Duarte, California, United States
Evangelische Lungenklinik Berlin
🇩🇪
Berlin, Germany
Texas Oncology, P.A.
🇺🇸
Bedford, Texas, United States
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
Hospital Universitario Vall d'Hebron
🇪🇸
Barcelona, Spain
Hospital Universitario Ramón y Cajal
🇪🇸
Madrid, Spain
East Valley Hematology and Oncology Medical Group, Inc.
🇺🇸
Burbank, California, United States
Compassionate Cancer Care Medical Group, Inc.
🇺🇸
Fountain Valley, California, United States
UC San Diego Moores Cancer Center
🇺🇸
La Jolla, California, United States
St. Joseph Heritage Healthcare
🇺🇸
Fullerton, California, United States
Sansum Clinic
🇺🇸
Santa Barbara, California, United States
The Oncology Institute of Hope and Innovation
🇺🇸
Whittier, California, United States
Florida Cancer Specialists
🇺🇸
Saint Petersburg, Florida, United States
Harry and Jeanette Weinberg Cancer Institute at Franklin Square
🇺🇸
Baltimore, Maryland, United States
Illinois Cancer Specialists
🇺🇸
Niles, Illinois, United States
University of Illinois Cancer Center
🇺🇸
Chicago, Illinois, United States
Regional Cancer Care Associates
🇺🇸
Morristown, New Jersey, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Regional Cancer Care Associates, LLC
🇺🇸
East Brunswick, New Jersey, United States
Texas Oncology, PA
🇺🇸
Austin, Texas, United States
Texas Oncology-Beaumont
🇺🇸
Beaumont, Texas, United States
Texas Oncology-Plano East
🇺🇸
Plano, Texas, United States
Asklepios Fachkliniken München-Gauting
🇩🇪
Gauting, Bayern, Germany
Yakima Valley Memorial Hospital, North Star Lodge
🇺🇸
Yakima, Washington, United States
Universitätsklinikum Köln
🇩🇪
Köln, Nordrhein-Westfalen, Germany
Ospedale Civile di Livorno
🇮🇹
Livorno, Italy
Katholisches Klinikum Mainz, Sankt Hildegardis-Krankenhaus
🇩🇪
Mainz, Rheinland-Pfalz, Germany
Queen Mary Hospital
🇭🇰
Hong Kong, Hong Kong
Inha University Hospital
🇰🇷
Incheon, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷
Seongnam-si, Korea, Republic of
Asan Medical Center
🇰🇷
Seoul, Korea, Republic of
The Catholic University of Korea Saint Vincent's Hospital
🇰🇷
Suwon, Korea, Republic of
Taipei Veterans General Hospital
🇨🇳
Taipei, Taiwan
Taichung Veterans General Hospital
🇨🇳
Taichung, Taiwan
Chang Gung Memorial Hospital Linkou
🇨🇳
Taoyuan, Taiwan
University of Southern California, Norris Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
Central Coast Medical Oncology Corporation
🇺🇸
Santa Maria, California, United States
Georgetown University Medical Center
🇺🇸
Washington, District of Columbia, United States
Cancer Specialists of North Florida
🇺🇸
Fleming Island, Florida, United States
Northwest Cancer Specialists, P.C.
🇺🇸
Vancouver, Washington, United States
Cleveland Clinic Florida
🇺🇸
Weston, Florida, United States
Pius Hospital Oldenburg
🇩🇪
Oldenburg, Niedersachsen, Germany
Severance Hospital, Yonsei University Health System
🇰🇷
Seoul, Korea, Republic of
Dong-A University Hospital
🇰🇷
Busan, Korea, Republic of
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Walter Reed Army Institute of Research
🇺🇸
Bethesda, Maryland, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
University of Colorado Cancer Center
🇺🇸
Aurora, Colorado, United States
Sutter Medical Group
🇺🇸
Sacramento, California, United States
Florida Hospital Cancer Institute
🇺🇸
Orlando, Florida, United States
Oncology Hematology West PC
🇺🇸
Omaha, Nebraska, United States
Hollings Cancer Center
🇺🇸
Charleston, South Carolina, United States
Montefiore Medical Center
🇺🇸
Bronx, New York, United States
Prince of Wales Hospital
🇭🇰
Hong Kong, New Territories, Hong Kong