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

Non-Small Cell Lung Cancer Clinical Trial

— EGFR  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02186301
• Other study ID #: CO-1686-022 (TIGER-1)
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: November 2014
• Est. completion date: June 28, 2017

Study information

• Verified date: April 2019
• Source: Clovis Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 100
• Est. completion date: June 28, 2017
• Est. primary completion date: June 28, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Rociletinib Mono-Therapy
Rociletinib will be administered twice daily
• Erlotinib Mono-Therapy
Erlotinib will be administered once a day

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Clovis Oncology, Inc.

Countries where clinical trial is conducted

United States,  Germany,  Hong Kong,  Italy,  Korea, Republic of,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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