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



Status:Terminated
Conditions:Lung Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:9/20/2018
Start Date:February 2015
End Date:March 29, 2018

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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.

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).

Inclusion Criteria:

All patients must meet all of the following 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
We found this trial at
32
sites
1801 Inwood Rd
Dallas, Texas 75390
(214) 645-3300
Principal Investigator: Randall Hughes
University of Texas Southwestern Medical Center UT Southwestern is an academic medical center, world-renowned for...
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666 Elm Street
Buffalo, New York 14263
(716) 845-2300
Principal Investigator: Hongbin Chen
Roswell Park Cancer Institute Welcome to Roswell Park Cancer Institute (RPCI), America's first cancer center...
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4100 John R
Detroit, Michigan 48201
800-527-6266
Principal Investigator: Shirish Gadgeel
Barbara Ann Karmanos Cancer Institute Karmanos is based in southeast Michigan, in midtown Detroit, and...
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220 S Palisade Dr # 204
Santa Maria, California 93454
Principal Investigator: Robert Dichmann
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291 Campus Dr
Stanford, California 94305
(650) 725-3900
Principal Investigator: Heather Wakelee
Stanford University School of Medicine Vast in both its physical scale and its impact on...
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5301 McAuley Drive
Ann Arbor, Michigan 48197
734-712-3456
Principal Investigator: Philip Stella
Saint Joseph Mercy Hospital St. Joseph Mercy Ann Arbor Hospital is a 537-bed teaching hospital...
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1000 Johnson Ferry Rd NE
Atlanta, Georgia 30342
(404) 851-8000
Principal Investigator: Rodolfo Bordoni
Northside Hospital Northside Hospital-Atlanta (in Sandy Springs) opened in 1970. The original facility had 250...
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Bakersfield, California 93309
Principal Investigator: Ravindranath (Ravi) Patel
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8901 Rockville Pike
Bethesda, Maryland 20889
(301) 295-4000
Principal Investigator: Christina Brzezniak
Walter Reed National Military Medical Center The Walter Reed National Military Medical Center is one...
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Charlottesville, Virginia 22903
(434) 924-0311
Principal Investigator: Richard Hall
University of Virginia The University of Virginia is distinctive among institutions of higher education. Founded...
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Columbus, Ohio 43210
Principal Investigator: Gregory Otterson
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Deerfield Beach, Florida 33442
Principal Investigator: Mohammad Jahanzeb
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Duarte, California 91010
Principal Investigator: Karen Reckamp
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East Brunswick, New Jersey 70072
Principal Investigator: Phillip Reid
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Evanston, Illinois 60201
Principal Investigator: Thomas Hensing
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Fullerton, California 92835
Principal Investigator: William Lawler
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1600 Southwest Archer Road
Gainesville, Florida 32610
Principal Investigator: Frederic Kaye
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La Jolla, California 92093
Principal Investigator: Lyudmila Bazhenova
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Minneapolis, Minnesota 55408
Principal Investigator: Joseph Leach
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Morristown, New Jersey 07962
Principal Investigator: Sarada Gurubhagavatula
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Pembroke Pines, Florida 33028
Principal Investigator: Luis Raez
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Pittsburgh, Pennsylvania 15232
Principal Investigator: Mark Socinski
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Portland, Oregon 97213
Principal Investigator: Rachel Sanborn
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Portland, Oregon 97239
Principal Investigator: Khaled Tolba
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Redondo Beach, California 90277
Principal Investigator: Thomas Lowe
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Richmond, Virginia 23235
Principal Investigator: Elke Friedman
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Sacramento, California 95816
Principal Investigator: Deepti Behl
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Saint Leonards, New South Wales 2065
Principal Investigator: Nick Pavlakis
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Salt Lake City, Utah 84112
Principal Investigator: Wallace Akerley, III
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San Francisco, California 94115
Principal Investigator: Collin Blakely
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405 Hilgard Avenue
Santa Monica, California 90404
Principal Investigator: Jonathan Goldman
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Whittier, California 90606
Principal Investigator: Merrill Shum
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