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 (EGFR)

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

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.

Study Overview

• Status: Terminated
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Erlotinib Mono-Therapy; Drug: Rociletinib Mono-Therapy

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).

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Evangelische Lungenklinik Berlin
  • Bayern
    • Gauting, Bayern, Germany, 82131
      • Asklepios Fachkliniken München-Gauting
  • Niedersachsen
    • Oldenburg, Niedersachsen, Germany, 26121
      • Pius Hospital Oldenburg
  • Nordrhein-Westfalen
    • Köln, Nordrhein-Westfalen, Germany, 50937
      • Universitätsklinikum Köln
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • Katholisches Klinikum Mainz, Sankt Hildegardis-Krankenhaus
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • New Territories
    • Hong Kong, New Territories, Hong Kong
      • Prince of Wales Hospital
• Italy
  • Livorno, Italy, 57124
    • Ospedale Civile di Livorno
• Korea, Republic of
  • Busan, Korea, Republic of, 602-715
    • Dong-A University Hospital
  • Incheon, Korea, Republic of, 400-711
    • Inha University Hospital
  • Seongnam-si, Korea, Republic of, 463-707
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital, Yonsei University Health System
  • Suwon, Korea, Republic of, 442-723
    • The Catholic University of Korea Saint Vincent's Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
• Taiwan
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan, 33305
    • Chang Gung Memorial Hospital Linkou
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • Burbank, California, United States, 91505
      • East Valley Hematology and Oncology Medical Group, Inc.
    • Duarte, California, United States, 91010
      • City of Hope
    • Fountain Valley, California, United States, 92708
      • Compassionate Cancer Care Medical Group, Inc.
    • Fullerton, California, United States, 92835-3825
      • St. Joseph Heritage Healthcare
    • La Jolla, California, United States, 92093-0698
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90089
      • University of Southern California, Norris Comprehensive Cancer Center
    • Sacramento, California, United States, 95816
      • Sutter Medical Group
    • San Francisco, California, United States, 94115
      • University of California San Francisco
    • Santa Barbara, California, United States, 93105
      • Sansum Clinic
    • Santa Maria, California, United States, 93454
      • Central Coast Medical Oncology Corporation
    • Santa Monica, California, United States, 90404
      • UCLA Medical Center
    • Whittier, California, United States, 90603
      • The Oncology Institute of Hope and Innovation
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Florida
    • Fleming Island, Florida, United States, 32003
      • Cancer Specialists of North Florida
    • Fort Myers, Florida, United States, 33916
      • Florida Cancer Specialists and Research Institute
    • Miami, Florida, United States, 33176
      • Advanced Medical Specialties
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Institute
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • University of Illinois Cancer Center
    • Niles, Illinois, United States, 60714
      • Illinois Cancer Specialists
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Harry and Jeanette Weinberg Cancer Institute at Franklin Square
    • Bethesda, Maryland, United States, 20889
      • Walter Reed Army Institute of Research
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Oncology Hematology West PC
  • Nevada
    • Henderson, Nevada, United States, 89014
      • Comprehensive Cancer Centers of Nevada
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Regional Cancer Care Associates, LLC
    • Morristown, New Jersey, United States, 07962
      • Regional Cancer Care Associates
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37212-3505
      • USC/Norris Comprehensive Cancer Center
  • Texas
    • Austin, Texas, United States, 78745
      • Texas Oncology, PA
    • Beaumont, Texas, United States, 77702
      • Texas Oncology-Beaumont
    • Bedford, Texas, United States, 76022
      • Texas Oncology, P.A.
    • Dallas, Texas, United States, 75390-8852
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Cancer Center
    • Houston, Texas, United States, 77030
      • The University of Texas - MD Anderson Cancer Center
    • Plano, Texas, United States, 75075-7753
      • Texas Oncology-Plano East
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington
    • Vancouver, Washington, United States, 98684
      • Northwest Cancer Specialists, P.C.
    • Yakima, Washington, United States, 98902
      • Yakima Valley Memorial Hospital, North Star Lodge

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Erlotinib Mono-Therapy	Drug: Erlotinib Mono-Therapy; Erlotinib will be administered once a day
Experimental: Rociletinib Mono-Therapy	Drug: Rociletinib Mono-Therapy; Rociletinib will be administered twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)	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.	Cycle 1 Day 1 to End of Treatment, up to approximately 35 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Response Rate	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.	Cycle 1 Day 1 to End of Treatment, up to approximately 35 months.
Duration of Response	Duration of Response in Patients with Confirmed Response per Investigator	Cycle 1 Day 1 to End of Treatment, up to approximately 35 months

Collaborators and Investigators

• Sponsor: Clovis Oncology, Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): June 28, 2017
• Study Completion (Actual): June 28, 2017

Study Registration Dates

• First Submitted: June 30, 2014
• First Submitted That Met QC Criteria: July 7, 2014
• First Posted (Estimate): July 10, 2014

Study Record Updates

• Last Update Posted (Actual): May 7, 2019
• Last Update Submitted That Met QC Criteria: April 29, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: lung; NSCLC; cancer; non-small cell lung cancer; EGFR; metastatic; recurrent; unresectable; locally advanced; T790M; epidermal growth factor receptor; irreversible EGFR inhibitor; CO-1686; EGFR-directed therapy; TIGER; rociletinib
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: CO-1686-022 (TIGER-1)