TIGER-3: Open Label, Multicenter Study of Rociletinib (CO-1686) Mono Therapy Versus Single-agent Cytotoxic Chemotherapy in Patients With Mutant EGFR NSCLC Who Have Failed at Least One Previous EGFR-Directed TKI and Platinum-doublet Chemotherapy

NCT ID: NCT02322281

Last Updated: 2019-08-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 149 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2018-03-29

Brief Summary

The purpose of this study is to compare the anti-tumor efficacy of oral single-agent rociletinib, as measured by investigator assessment of the PFS, with that of single-agent cytotoxic chemotherapy in patients with EGFR-mutated, advanced/metastatic NSCLC after failure of at least 1 previous EGFR-directed TKI and at least 1 line of platinum-containing doublet chemotherapy.

Detailed Description

This is a Phase 3, randomized, open-label, multicenter study evaluating the safety and efficacy of oral rociletinib at 500 mg BID and 625 mg BID compared with that of single-agent cytotoxic chemotherapy, in patients with previously treated mutant EGFR NSCLC. Eligible patients are those with mutant EGFR NSCLC previously treated with at least 1 EGFR inhibitor and at least 1 line of platinum-containing chemotherapy doublet for advanced/metastatic NSCLC.

After providing informed consent to participate and screening to confirm eligibility, patients will be randomized 1:1:1 to receive either oral rociletinib 500 mg BID, oral rociletinib 625 mg BID, or single-agent cytotoxic chemotherapy (investigator choice of pemetrexed, gemcitabine, docetaxel, or paclitaxel; choice of chemotherapy agent must be specified before randomization).

Conditions

Non-small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rociletinib Monotherapy (500 mg BID)

Daily oral rociletinib at 500 mg BID with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Treatment with rociletinib is continuous and each cycle will comprise of 21 days.

Group Type: EXPERIMENTAL

Rociletinib

Intervention Type: DRUG

Rociletinib Monotherapy (625 mg BID)

Daily oral rociletinib at 625 mg BID with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Treatment with rociletinib is continuous and each cycle will comprise of 21 days.

Group Type: EXPERIMENTAL

Rociletinib

Intervention Type: DRUG

Pemetrexed or gemcitabine or paclitaxel or docetaxel

Pemetrexed

500 mg/m2 pemetrexed given intravenously on Day 1 of each 21-day cycle.

Gemcitabine

1250 mg/m2 gemcitabine given intravenously on Day 1 and 8 of each 21-day cycle.

Docetaxel

75 mg/m2 docetaxel (60 mg/m2 for patients residing in East-Asian territories) given intravenously on Day 1 of each 21-day cycle.

or 35 mg/m2 docetaxel given intravenously on a weekly basis as part of a continuous 21-day cycle; i.e. dosing will be on Days 1, 8, and 15 of each 21-day cycle.

Paclitaxel

80 mg/m2 paclitaxel given intravenously on a weekly basis as part of a continuous 21-day cycle; i.e. dosing will be on Days 1, 8, and 15 of each 21-day cycle.

Group Type: ACTIVE_COMPARATOR

Pemetrexed or gemcitabine or paclitaxel or docetaxel

Intervention Type: DRUG

Interventions

Rociletinib

Intervention Type: DRUG

Pemetrexed or gemcitabine or paclitaxel or docetaxel

Intervention Type: DRUG

Other Intervention Names

CO-1686

Eligibility Criteria

Inclusion Criteria

1. Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with radiological progression on the most recent therapy received

2. Documented evidence of a tumor with 1 or more EGFR activating mutations excluding exon 20 insertion

3. Disease progression confirmed by radiological assessment while receiving treatment with single agent EGFR-TKI (e.g., erlotinib, gefitinib, afatinib, or dacomitinib) or EGFR-TKI in combination with other targeted therapy (e.g. bevacizumab, immunotherapy)

4. Multiple lines of prior treatment are permitted and there is no specified order of treatment, but in the course of their treatment history, patients must have received and have radiologically documented disease progression following:

At least 1 line of prior treatment with a single-agent EGFR-TKI (e.g., erlotinib, gefitinib, afatinib, or dacomitinib)

If EGFR-TKI is a component of the most recent treatment line, the washout period for the EGFR-TKI is a minimum of 3 days before the start of study drug treatment

AND

A platinum-containing doublet chemotherapy (either progressed during therapy or completed at least 4 cycles without progression with subsequent progression after a treatment-free interval or after a maintenance treatment).

If cytotoxic chemotherapy is a component of the most recent treatment line, treatment with chemotherapy should have been completed at least 14 days prior to start of study treatment. When an EGFR-TKI is given in combination with platinum-containing doublet chemotherapy, treatment with the EGFR-TKI may continue until at least 3 days before start of treatment.

5. Have undergone a biopsy of either primary or metastatic tumor tissue within 60 days prior to start of treatment and have tissue sent to the central laboratory prior to randomization

6. Measureable disease according to RECIST Version 1.1

7. Life expectancy of at least 3 months

8. ECOG performance status of 0 to 1

9. Age ≥ 18 years (in certain territories, the minimum age requirement may be higher e.g., age ≥ 20 years in Japan and Taiwan, age ≥ 21 years in Singapore)

10. Patients should have recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤ 1 from any significant chemotherapy-related toxicities

11. Adequate hematological and biological function

12. Written consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF before any study specific evaluation

Exclusion Criteria

Any of the following criteria will exclude patients from study participation:

1. Any other malignancy associated with a high mortality risk within the next 5 years and for which the patients 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 enroll in the trial provided all chemotherapy was completed > 6 months prior and/or bone marrow transplant > 2 years prior

2. Known pre-existing interstitial lung disease

3. Tumor small cell transformation by local assessment, irrespective of presence of T790M+ component

4. Patients with leptomeningeal carcinomatosis are excluded. Other central nervous system (CNS) metastases are only permitted if treated, asymptomatic, and stable (not requiring steroids for at least 2 weeks prior to randomization and the patient is neurologically stable i.e. free from new symptoms of brain metastases)

5. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and that treatment cannot be either discontinued or switched to a different medication (known to have no effect on QT) before starting protocol-specified treatment (see http://crediblemeds.org/ for a list of QT-prolonging medications)

6. Prior treatment with rociletinib, or other drugs that target T790M+ mutant EGFR with sparing of WT-EGFR including but not limited to osimertinib, HM61713, and TAS-121

7. Any contraindications for therapy with pemetrexed, paclitaxel, gemcitabine or docetaxel unless a contraindication with respect to one of these drugs will not affect the use of any of the others as a comparator to rociletinib

8. Any of the following cardiac abnormalities or history:

1. Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTCF) > 450 msec

2. Inability to measure QT interval on ECG

3. Personal or family history of long QT syndrome

4. Implantable pacemaker or implantable cardioverter defibrillator

5. Resting bradycardia < 55 beats/min

9. Non-study related surgical procedures ≤ 7 days prior to randomization. In all cases, the patient must be sufficiently recovered and stable before treatment administration

10. Females who are pregnant or breastfeeding

11. Refusal to use adequate contraception for fertile patients (females and males) while on treatment and for 6 months after the last dose of study treatment (rociletinib and chemotherapy irrespective of single cytotoxic agent used)

12. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled intercurrent illness including uncontrolled diabetes, active infection, arterial thrombosis, and symptomatic pulmonary embolism)

13. Any other reason the investigator considers the patient should not participate in the study

14. Treatment with live vaccines initiated less than 4 weeks prior to randomization

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clovis Oncology, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Comprehensive Blood and Cancer Center

Bakersfield, California, United States

City of Hope Cancer Center

Duarte, California, United States

Saint Joseph Heritage Healthcare

Fullerton, California, United States

University of California San Diego Moores Cancer Center

La Jolla, California, United States

Cancer Care Associates Medical Group, Inc.

Redondo Beach, California, United States

Sutter Cancer Center

Sacramento, California, United States

University of California, San Francisco Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Central Coast Medical Oncology Corporation

Santa Maria, California, United States

University of California at Los Angeles

Santa Monica, California, United States

Stanford University School of Medicine

Stanford, California, United States

The Oncology Institute of Hope and Innovation

Whittier, California, United States

Sylvester Comprehensive Cancer Center (UMHC)

Deerfield Beach, Florida, United States

University of Florida Health Science Center

Gainesville, Florida, United States

Memorial Healthcare System

Pembroke Pines, Florida, United States

Northside Hospital

Atlanta, Georgia, United States

North Shore University Health System

Evanston, Illinois, United States

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Virginia Piper Cancer Institute

Minneapolis, Minnesota, United States

Regional Cancer Care Associates, LLC

East Brunswick, New Jersey, United States

Regional Cancer Care Associates

Morristown, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Providence Health and Services

Portland, Oregon, United States

Oregon Health & Science University (OHSU) - Knight Cancer Institute

Portland, Oregon, United States

University of Pittsburgh Cancer Institute (UPMC)

Pittsburgh, Pennsylvania, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

University of Virginia

Charlottesville, Virginia, United States

Virginia Cancer Institute

Richmond, Virginia, United States

Royal North Shore Hospital

Saint Leonards, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Flinders Medical Centre

Bedford Park, South Australia, Australia

Hopital Hautepierre (CHU) de Strasbourg

Strasbourg, Alsace, France

Centre François Baclesse

Caen, Basse-Normandie, France

Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou

Rennes, Brittany Region, France

CHRU de Lille - Hôpital Calmette

Lille, Hauts-de-France, France

CHRU de Limoges - Hôpital Dupuytren

Limoges, Limousin, France

L'Assistance Publique - Hopitaux de Marseille

Marseille, Provence-Alpes-Côte d'Azur Region, France

Centre Léon Bérard

Lyon, , France

Centre Hospitalier Intercommunal Créteil

Créteil, Île-de-France Region, France

Hôpital Bichat-Claude Bernard

Paris, Île-de-France Region, France

Asklepios Fachkliniken München-Gauting

Gauting, Baden-Wurttemberg, Germany

Thoraxklinik Heidelberg gGmbH

Heidelberg, Baden-Wurttemberg, Germany

LMU - Klinikum der Universität München

München, Bavaria, Germany

Pius Hospital Oldenburg

Oldenburg, Niedersachen, Germany

Johannes-Wesling-Klinikum Minden

Minden, North Rhine-Westphalia, Germany

LungenClinic Großhansdorf GmbH

Großhansdorf, Schleswig-Holstein, Germany

A.O.U. San Luigi Gonzaga di Orbassano

Orbassano, Torino, Italy

Azienda Ospedaliero-Universitaria Careggi

Florence, , Italy

IRCCS Azienda Ospedaliera Universitaria San Martino - IST

Genova, , Italy

Ospedale Civile di Livorno

Livorno, , Italy

Istituto Europeo di Oncologia

Milan, , Italy

Azienda Ospedaliera di Perugia

Perugia, , Italy

Academisch Ziekenhuis Maastricht

Maastricht, Limburg, Netherlands

Antoni van Leeuwenhoek Hospital

Amsterdam, North Holland, Netherlands

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Chungbuk National University Hospital

Cheongju-si, Cheungcheongbuk-do, South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

The Catholic University of Korea Saint Vincent's Hospital

Suwon, Gyeonggi-do, South Korea

Chonnam National University Hwasun Hospital

Hwasun-gun, Jeollanam-do, South Korea

Samsung Medical Center

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital de Mataró

Mataró, Barcelona, Spain

Institut Universitari Dexeus

Barcelona, , Spain

Hospital Universitari Vall D'Hebron

Barcelona, , Spain

Fundacion Jimenez Diaz (Clinica de la Concepcion) (UAM -FJD)

Madrid, , Spain

Hospital Regional Universitario Carlos Haya

Málaga, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

China Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Cheng-Kung University Hospital

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

University College London Hospitals

London, England, United Kingdom

Guy's and Saint Thomas NHS Foundation Trust

London, England, United Kingdom

Royal Marsden NHS Trust

London, England, United Kingdom

The Christie NHS Foundation Trust

Manchester, England, United Kingdom

Countries

United States; Australia; France; Germany; Italy; Netherlands; South Korea; Spain; Taiwan; United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CO-1686-020 (TIGER-3)

Identifier Type: -

Identifier Source: org_study_id