Multicenter Study of Rociletinib Administered to Patients With Previously Treated Mutant EGFR Non-small Cell Lung Cancer

NCT02147990 | Terminated Phase 2 Results

• 1 other identifier: CO-1686-019 (TIGER-2)
• Study Type: interventional
• Target: 318
• Locations: 12 countries
• Sites: 91

Brief Summary

The purpose of this study is to evaluate the safety and anti-tumor effect of rociletinib. The trial is open-ended, which means patients will continue to take rociletinib until the study doctor determines it is no longer beneficial for them.

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) According to RECIST Version 1.1 as Determined by Investigator Assessment

  ORR is defined as the percentage 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. For patients who continued treatment post-progression, the first date of progression was used for the analysis. 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.

  Cycle 1 Day 1 to End of Treatment, up to approximately 57 months.

Secondary Outcomes (18)

• Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment

  From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 54 months

• Disease Control Rate (DCR) by RECIST v1.1 as Determined by Investigator Assessment

  From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 57 months

• Progression-free Survival (PFS) in T790M Positive Patients by RECIST v1.1 as Determined by Investigator Assessment

  From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 57 months

• Overall Survival (OS) Determined by Investigator Assessment

  Cycle 1 Day 1 to date of death, assessed up to 57 months

• Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Scale

  Baseline (Day 0), Months 5, 10 and EOT

Study Arms (3)

Rociletinib Mono-Therapy, T790M +ve (625mg BID)

EXPERIMENTAL

Starting dose of 625mg rociletinib, taken orally twice daily, with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Tablets should be swallowed whole. Treatment with rociletinib is continuous and each cycle will comprise of 28 days.

Drug: Rociletinib

Rociletinib Mono-Therapy, T790M +ve (500mg BID)

EXPERIMENTAL

Starting dose of 500mg rociletinib, taken orally twice daily, with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Tablets should be swallowed whole. Treatment with rociletinib is continuous and each cycle will comprise of 28 days.

Drug: Rociletinib

Rociletinib Mono-Therapy, T790M -ve (500mg BID)

EXPERIMENTAL

Starting dose of 500mg rociletinib, taken twice daily, with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Tablets should be swallowed whole. Treatment with rociletinib is continuous and each cycle will comprise of 28 days.

Drug: Rociletinib

Interventions

Rociletinib DRUG

Rociletinib will be administered to patients orally

Also known as: CO-1686

Rociletinib Mono-Therapy, T790M +ve (500mg BID); Rociletinib Mono-Therapy, T790M +ve (625mg BID); Rociletinib Mono-Therapy, T790M -ve (500mg BID)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC
• Documented evidence of a tumor with 1 or more EGFR mutations excluding exon 20 insertion
• Disease progression confirmed by radiologic assessment while receiving treatment with the first single agent EGFR-TKI
• EGFR TKI treatment discontinued less than or equal to 30 days prior to planned initiation of rociletinib
• The washout period for an EGFR inhibitor is a minimum of 3 days
• No intervening treatment between cessation of single agent EGFR TKI and planned initiation of rociletinib
• Previous treatment with less than or equal to 1 prior chemotherapy (excluding prior neo-adjuvant or adjuvant chemotherapy or chemoradiotherapy with curative intent)
• Any toxicity related to prior EGFR inhibitor treatment must have resolved to Grade 1 or less
• Central laboratory confirmation of the presence of the T790M mutation in tumor tissue in Cohort A and the presence or absence of the T790M mutation in tumor tissue in Cohort B. Centrally indeterminate, unknown or invalid specimens are not acceptable. Biopsy material obtained from either primary or metastatic tumor tissue and sent to the central laboratory must be within 60 prior to dosing study drug but following disease progression on the first EGFR TKI
• Measurable disease according to RECIST Version 1.1
• Life expectancy of at least 3 months
• ECOG performance status of 0 to 1
• Minimum Age 18 years (in certain territories, the minimum age requirement may be higher eg age 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

You may not qualify if:

• Documented evidence of an exon 20 insertion activating mutation in the EGFR gene
• 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, with no evidence of that cancer currently, are permitted to enrol in the trial provided all chemotherapy was completed greater than 6 months prior and/or bone marrow transplant greater than 2 years prior
• Known pre-existing interstitial lung disease
• Cohort A only: Patients with leptomeningeal carcinomatosis are excluded. Other central nervous system (CNS) metastases are only permitted if treated, asymptomatic, and stable (not requiring steroid for at least 4 weeks prior to the start of study treatment). Cohort B only: Patients with CNS metastases or leptomeningeal carcinomatosis are excluded.
• Treatment with prohibited medications less than or equal to 14 days prior to treatment with rociletinib
• Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication before starting rociletinib
• Prior treatment with rociletinib, or other drugs that target T790M positive mutant EGFR with sparing of wild type EGFR
• Any of the following cardiac abnormalities or history
• Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTCF) greater than 450 msec
• Inability to measure QT interval on ECG
• Personal or family history of long QT syndrome
• Implantable pacemaker or implantable cardioverter defibrillator
• Resting bradycardia less than 55 beats/min
• Non-study related surgical procedures less than or equal to 7 days prior to administration of rociletinib. In all cases, the patient must be sufficiently recovered and stable before treatment administration

Sponsors & Collaborators

• Clovis Oncology, Inc.: lead

Study Sites (91)

UCLA Medical Center

Alhambra, California, 91801, United States

Location

Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

Location

Saint Jude Heritage Healthcare

Fullerton, California, 92835, United States

Location

University of California San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Northridge Hospital Medical Center

Northridge, California, 91328, United States

Location

Cancer Care Associates

Redondo Beach, California, 90277, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

University of California San Francisco

San Francisco, California, 94115, United States

Location

Coastal Integrative Cancer Care

San Luis Obispo, California, 93401, United States

Location

Saint Mary's Regional Cancer Center

Grand Junction, Colorado, 81501-6132, United States

Location

Rocky Mountain Cancer Centers, LLP

Lone Tree, Colorado, 80218, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 32135, United States

Location

Advanced Medical Specialties

Miami, Florida, 33176, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

University of Illinois Chicago

Chicago, Illinois, 60612, United States

Location

Illinois Cancer Specialists

Niles, Illinois, 60714, United States

Location

Beth Israel Comprehensive Cancer Center

Boston, Massachusetts, 02215, United States

Location

Lahey Hospital and Medical Center

Burlington, Massachusetts, 01805, United States

Location

Minnesota Oncology Hematology, P.A

Minneapolis, Minnesota, 55404, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

New York Oncology Hematology, PC

Latham, New York, 12110-2188, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Texas Oncology P.A.

Amarillo, Texas, 79106, United States

Location

USO - Texas Oncology P.A.

Arlington, Texas, 76014, United States

Location

Texas Oncology-Austin Central

Austin, Texas, 78705, United States

Location

Texas Oncology-Beaumont

Beaumont, Texas, 77702, United States

Location

Texas Oncology P.A.

Bedford, Texas, 76022, United States

Location

Texas Oncology P.A.

Dallas, Texas, 75246, United States

Location

Texas Oncology P.A.

Flower Mound, Texas, 75028, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Oncology - Plano East

Plano, Texas, 75075-7787, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Northwest Cancer Specialists, P.C.

Vancouver, Washington, 98686, United States

Location

Yakima Valley Memorial Hospital, North Star Lodge

Yakima, Washington, 98902, United States

Location

Icon Cancer Centre

South Brisbane, New South Wales, 4101, Australia

Location

Royal North Shore Hospital

Sydney, New South Wales, 2065, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2L7, Canada

Location

Centre Hospitalier Lyon Sud

Pierre Bénité Cedex, Auvergne-Rhône-Alpes, 69495, France

Location

Centre Hospitalier Regional Universitaire (CHRU) de Besancon - L'Hopital Jean Minjoz

Besançon, Franche-comte, 25030 cedex, France

Location

Institut de Cancérologie de l'Ouest - René Gauducheau

Saint-Herblain, Pays de la Loire Region, France

Location

Centre Hospitalier Universitaire Côte de Nacre

Caen, France

Location

Centre Hospitalier Universitaire Hôpital Nord

Marseille, 13915, France

Location

Hôpital Tenon

Paris, Île-de-France Region, 75020, France

Location

Institut Gustave Roussy

Villejuif, Île-de-France Region, 94805, France

Location

Asklepios Fachkliniken München-Gauting

Gauting, Bavaria, 82131, Germany

Location

Klinikum Innenstadt LMU

München, Bavaria, 80336, Germany

Location

Goethe-Universität Frankfurt am Main

Frankfurt am Main, Hesse, 60590, Germany

Location

Pius Hospital Oldenburg

Oldenburg, Lower Saxony, 26121, Germany

Location

Universitaetsklinikum Bonn - Zentrum fuer Innere Medizin - Medizinische Klinik und Poliklink III

Bonn, North Rhine-Westphalia, 53127, Germany

Location

Universitätsklinikum Köln

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, 45122, Germany

Location

LungenClinic Großhansdorf GmbH

Großhansdorf, Schleswig-Holstein, 22927, Germany

Location

Evangelische Lungenklinik Berlin

Berlin, 13125, Germany

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Antoni van Leeuwenhoek Hospital

Amsterdam, North Holland, 1066 CX, Netherlands

Location

Vrije Universiteit Medisch Centrum

Amsterdam, 1081 HV, Netherlands

Location

National Cancer Center

Goyang-si, Gyeonggi-do, South Korea

Location

Gachon University Gil Medical Center

Incheon, Gyeonggi-do, 405-760, South Korea

Location

Chungbuk National University Hospital

Chungju, North Chungcheong, South Korea

Location

Dong-A University Hospital

Busan, South Korea

Location

Inha University Hospital

Incheon, 400-711, South Korea

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Seoul Saint Mary's Hospital

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

Hospital Universitario Virgen del Rocio

Seville, Sevilla, 41013, Spain

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Spain

Location

Hospital Vall d´Hebrón

Barcelona, 08035, Spain

Location

Hospital Universitario Quirón Dexeus

Barcelona, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Centre Hospitalier Universitaire Vaudoise

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Taipei Veterans General Hospital

Taipei, Taipei CITY, 11217, Taiwan

Location

Chang Gung Memorial Hospital Linkou

Taoyuan District, Tao-Yuan, 33305, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, England, CB2 0QQ, United Kingdom

Location

Guy's and Saint Thomas NHS Foundation Trust

London, Greater London, SE1 9RT, United Kingdom

Location

Royal Marsden Hospital

London, Greater London, SW3 6JJ, United Kingdom

Location

Royal Marsden NHS Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

University College Hospital

London, NW1 2PQ, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms; Neoplasm Metastasis; Recurrence

Interventions

rociletinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Results Point of Contact

• Title: Medical Information Department
• Organization: Clovis Oncology, Inc.

medinfo@clovisoncology.com

+1 415 409 7220

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2014
• First Posted: May 28, 2014
• Study Start: June 16, 2014
• Primary Completion: July 30, 2019
• Study Completion: August 27, 2019
• Last Updated: August 12, 2020
• Results First Posted: August 12, 2020

Record last verified: 2020-07

Locations

CH (1); KR (10); ES (5); HK (1); NL (2); US (41); FR (7); TW (5); CA (1); AU (4); GB (5); DE (9)