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AzTrials

Non-small Cell Lung CancerPhase 3NCT02322281

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

A Phase 3 study testing Rociletinib and Pemetrexed or gemcitabine or paclitaxel or docetaxel in people with Non-small Cell Lung Cancer, run by Clovis Oncology, Inc. at 80 sites in 10 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
Rociletinib and Pemetrexed or gemcitabine or paclitaxel or docetaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
149 participants
Where
80 sitesin 10 countries
Study dates
Feb 2015to 29 Mar 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • All patients must meet all of the following inclusion criteria:
  • Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with radiological progression on the most recent therapy received
  • Documented evidence of a tumor with 1 or more EGFR activating mutations excluding exon 20 insertion
  • 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)
  • 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)
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  • 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.
  • 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
  • Measureable disease according to RECIST Version 1.1
  • Life expectancy of at least 3 months
  • ECOG performance status of 0 to 1
  • 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)
  • Patients should have recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤ 1 from any significant chemotherapy-related toxicities
  • Adequate hematological and biological function
  • Written consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF before any study specific evaluation

Who cannot join

  • Any of the following criteria will exclude patients from study participation:
  • 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
  • Known pre-existing interstitial lung disease
  • Tumor small cell transformation by local assessment, irrespective of presence of T790M+ component
  • 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)
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  • 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)
  • 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
  • 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
  • Any of the following cardiac abnormalities or history:
  • Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTCF) > 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 < 55 beats/min
  • Non-study related surgical procedures ≤ 7 days prior to randomization. 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) while on treatment and for 6 months after the last dose of study treatment (rociletinib and chemotherapy irrespective of single cytotoxic agent used)
  • 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)
  • Any other reason the investigator considers the patient should not participate in the study
  • Treatment with live vaccines initiated less than 4 weeks prior to randomization

Trial locations and contacts

80 sites in 10 countries.

80 sites in 10 countries

United States31 sites

  • Saint Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106

  • Northside Hospital

    Atlanta, Georgia, 30341

  • Comprehensive Blood and Cancer Center

    Bakersfield, California, 93309

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University of Virginia

    Charlottesville, Virginia, 22903

  • The Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Sylvester Comprehensive Cancer Center (UMHC)

    Deerfield Beach, Florida, 33442

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • City of Hope Cancer Center

    Duarte, California, 91010

  • Regional Cancer Care Associates, LLC

    East Brunswick, New Jersey, 08816

  • North Shore University Health System

    Evanston, Illinois, 60201

  • Saint Joseph Heritage Healthcare

    Fullerton, California, 92835

  • University of Florida Health Science Center

    Gainesville, Florida, 32608

  • University of California San Diego Moores Cancer Center

    La Jolla, California, 92093-0698

  • Virginia Piper Cancer Institute

    Minneapolis, Minnesota, 55407

  • Regional Cancer Care Associates

    Morristown, New Jersey, 07962

  • Memorial Healthcare System

    Pembroke Pines, Florida, 33028

  • University of Pittsburgh Cancer Institute (UPMC)

    Pittsburgh, Pennsylvania, 15232

  • Providence Health and Services

    Portland, Oregon, 97223

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

    Portland, Oregon, 97239

  • Cancer Care Associates Medical Group, Inc.

    Redondo Beach, California, 90277

  • Virginia Cancer Institute

    Richmond, Virginia, 23230

  • Sutter Cancer Center

    Sacramento, California, 95816

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

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

    San Francisco, California, 94115

  • Central Coast Medical Oncology Corporation

    Santa Maria, California, 93454

  • University of California at Los Angeles

    Santa Monica, California, 90404

  • Stanford University School of Medicine

    Stanford, California, 94305

  • The Oncology Institute of Hope and Innovation

    Whittier, California, 90603

Other trials in United States

France9 sites

  • Centre François Baclesse

    Caen, Basse-Normandie, 14076

  • Centre Hospitalier Intercommunal Créteil

    Créteil, Île-de-France Region, 94010

  • CHRU de Lille - Hôpital Calmette

    Lille, Hauts-de-France, 59037

  • CHRU de Limoges - Hôpital Dupuytren

    Limoges, Limousin, 87042

  • Centre Léon Bérard

    Lyon, 69373

  • L'Assistance Publique - Hopitaux de Marseille

    Marseille, Provence-Alpes-Côte d'Azur Region, 13009

  • Hôpital Bichat-Claude Bernard

    Paris, Île-de-France Region, 75018

  • Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou

    Rennes, Brittany Region, 35033

  • Hopital Hautepierre (CHU) de Strasbourg

    Strasbourg, Alsace, 67091

Other trials in France

Spain7 sites

  • Hospital Universitari Germans Trias i Pujol

    Badalona, Barcelona, 08916

  • Institut Universitari Dexeus

    Barcelona, 08028

  • Hospital Universitari Vall D'Hebron

    Barcelona, 08035

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

    Madrid, 28040

  • Hospital Regional Universitario Carlos Haya

    Málaga, 29010

  • Hospital de Mataró

    Mataró, Barcelona, 08034

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

Other trials in Spain

Germany6 sites

  • Asklepios Fachkliniken München-Gauting

    Gauting, Baden-Wurttemberg, 82131

  • LungenClinic Großhansdorf GmbH

    Großhansdorf, Schleswig-Holstein, 22927

  • Thoraxklinik Heidelberg gGmbH

    Heidelberg, Baden-Wurttemberg, 69126

  • Johannes-Wesling-Klinikum Minden

    Minden, North Rhine-Westphalia, 32429

  • LMU - Klinikum der Universität München

    München, Bavaria, 80336

  • Pius Hospital Oldenburg

    Oldenburg, Niedersachen, 26121

Other trials in Germany

Italy6 sites

  • Azienda Ospedaliero-Universitaria Careggi

    Florence, 50139

  • IRCCS Azienda Ospedaliera Universitaria San Martino - IST

    Genova, 16132

  • Ospedale Civile di Livorno

    Livorno, 57124

  • Istituto Europeo di Oncologia

    Milan, 20141

  • A.O.U. San Luigi Gonzaga di Orbassano

    Orbassano, Torino, 10043

  • Azienda Ospedaliera di Perugia

    Perugia, 06132

Other trials in Italy

South Korea6 sites

  • Chungbuk National University Hospital

    Cheongju-si, Cheungcheongbuk-do, 361-712

  • Chonnam National University Hwasun Hospital

    Hwasun-gun, Jeollanam-do, 519-809

  • Seoul National University Bundang Hospital

    Seongnam-si, Gyeonggi-do, 463-707

  • Samsung Medical Center

    Seoul, 135-710

  • Asan Medical Center

    Seoul, 138-736

  • The Catholic University of Korea Saint Vincent's Hospital

    Suwon, Gyeonggi-do, 442-723

Other trials in South Korea

Taiwan5 sites

  • China Medical University Hospital

    Taichung, 40447

  • Taichung Veterans General Hospital

    Taichung, 40705

  • National Cheng-Kung University Hospital

    Tainan, 70403

  • National Taiwan University Hospital

    Taipei, 10002

  • Taipei Veterans General Hospital

    Taipei, 11217

Other trials in Taiwan

United Kingdom4 sites

  • University College London Hospitals

    London, England, NW1 2BU

  • Guy's and Saint Thomas NHS Foundation Trust

    London, England, SE1 9RT

  • Royal Marsden NHS Trust

    London, England, SW3 6JJ

  • The Christie NHS Foundation Trust

    Manchester, England, M20 4BX

Other trials in United Kingdom

Australia3 sites

  • Flinders Medical Centre

    Bedford Park, South Australia, 5042

  • Royal North Shore Hospital

    Saint Leonards, New South Wales, 2065

  • Westmead Hospital

    Westmead, New South Wales, 2145

Other trials in Australia

Netherlands3 sites

  • Antoni van Leeuwenhoek Hospital

    Amsterdam, North Holland, 1066 CX

  • Universitair Medisch Centrum Groningen

    Groningen, 9700 RB

  • Academisch Ziekenhuis Maastricht

    Maastricht, Limburg, 6229 HX

Other trials in Netherlands

About this study

Official title: TIGER-3: A Phase 3, Open-label, Multicenter, Randomized Study of Oral Rociletinib (CO-1686) Monotherapy Versus Single-agent Cytotoxic Chemotherapy in Patients With Mutant EGFR Non-small Cell Lung Cancer (NSCLC) After Failure of at Least 1 Previous EGFR-directed Tyrosine Kinase Inhibitor (TKI) and Platinum-doublet Chemotherapy

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.

Read the 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).

Being tested
Rociletinib, Pemetrexed or gemcitabine or paclitaxel or docetaxel
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
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Neoplasms, Neoplasm Metastasis, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RociletinibDrug

    Also called CO-1686

  • Pemetrexed or gemcitabine or paclitaxel or docetaxelDrug

Study groups in NCT02322281
Study groupRoleWhat they receive
Rociletinib Monotherapy (500 mg BID)ExperimentalDaily 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.
Receives: Drug: Rociletinib
Rociletinib Monotherapy (625 mg BID)ExperimentalDaily 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.
Receives: Drug: Rociletinib
Pemetrexed or gemcitabine or paclitaxel or docetaxelActive comparatorPemetrexed 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.
Receives: Drug: Pemetrexed or gemcitabine or paclitaxel or docetaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)

    PFS was calculated as 1+ the number of days from the date of randomization to documented radiographic progression as determined by the investigator, or death due to any cause, whichever occurs first. 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.

    Measured: Cycle 1 Day 1 to End of Treatment, up to approximately 35 months. This Time Frame includes the cross-over period, however, participants who crossed over to rociletinib were not analyzed for PFS.

Secondary outcomes (4)

  1. Percentage of Participants With Confirmed Response

    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 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.

    Measured: Cycle 1 Day 1 to End of Treatment, up to approximately 35 months. This Time Frame includes the cross-over period, however, participants who crossed over to rociletinib were not analyzed for best overall confirmed response.

  2. Duration of Response (DOR) According to RECIST Version 1.1 as Determined by Investigator Assessment

    DOR in patients with confirmed response per investigator. The DOR for complete response (CR) and partial response (PR) was measured from date that any of these best responses is first recorded until first date that progressive disease (PD) is objectively documented. For patients who continue 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: CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. PR is at least a 30% decrease in sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Overall Response is the best response from start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

    Measured: Cycle 1 Day 1 to End of Treatment, up to approximately 35 months

  3. Overall Survival (OS)

    OS was calculated as 1+ the number of days from randomization to death due to any cause. Patients without a documented date of death were censored on the date the patient was last known to be alive.

    Measured: Cycle 1 Day 1 to date of death, assessed up to 3 years

  4. Plasma PK for Patients Treated With Rociletinib Based on Sparse Sampling

    Blood samples were drawn for PK analysis at 21 ± 3 day intervals for the first 6 months (Day 1 of Cycles 2 to 7 inclusive). The sample could be taken predose or postdose. Plasma concentrations are presented for Rociletinib and 3 metabolites (M460, M502, M544).

    Measured: Cycles 2 Day 1 to Cycle 7 Day 1, or approximately 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Dec 2014 (estimated)
  2. Study startFeb 2015
  3. Primary completion29 Mar 2018
  4. Study completion29 Mar 2018

Why it stopped: Sponsor discontinued development of CO-1686 for NSCLC

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
149 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02322281
Sponsor's protocol ID
CO-1686-020 (TIGER-3)
Status last verified
Jul 2019
First submitted
17 Dec 2014
Last updated
14 Aug 2019
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Rociletinib and Pemetrexed or gemcitabine or paclitaxel or docetaxel in people with Non-small Cell Lung Cancer, run by Clovis Oncology, Inc. at 80 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 80 sites in United States, France, Spain, Germany, Italy and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS) (time frame: Cycle 1 Day 1 to End of Treatment, up to approximately 35 months. This Time Frame includes the cross-over period, however, participants who crossed over to rociletinib were not analyzed for PFS.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02322281.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2019.

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