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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02322281




Registration number
NCT02322281
Ethics application status
Date submitted
17/12/2014
Date registered
23/12/2014
Date last updated
14/08/2019

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
CO-1686-020 (TIGER-3)
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Rociletinib
Treatment: Drugs - Pemetrexed or gemcitabine or paclitaxel or docetaxel

Experimental: 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.

Experimental: 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.

Active Comparator: 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.


Treatment: Drugs: Rociletinib


Treatment: Drugs: Pemetrexed or gemcitabine or paclitaxel or docetaxel


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
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 outcome [1] 0 0
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.
Timepoint [1] 0 0
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.
Secondary outcome [2] 0 0
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).
Timepoint [2] 0 0
Cycle 1 Day 1 to End of Treatment, up to approximately 35 months
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Cycle 1 Day 1 to date of death, assessed up to 3 years
Secondary outcome [4] 0 0
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).
Timepoint [4] 0 0
Cycles 2 Day 1 to Cycle 7 Day 1, or approximately 6 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
5042 - Bedford Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Utah
Country [15] 0 0
United States of America
State/province [15] 0 0
Virginia
Country [16] 0 0
France
State/province [16] 0 0
Alsace
Country [17] 0 0
France
State/province [17] 0 0
Basse-Normandie
Country [18] 0 0
France
State/province [18] 0 0
Bretagne
Country [19] 0 0
France
State/province [19] 0 0
Ile-de-France
Country [20] 0 0
France
State/province [20] 0 0
Limousin
Country [21] 0 0
France
State/province [21] 0 0
Nord Pas-de-Calais
Country [22] 0 0
France
State/province [22] 0 0
Provence Alpes Cote D'Azur
Country [23] 0 0
France
State/province [23] 0 0
Lyon
Country [24] 0 0
Germany
State/province [24] 0 0
Baden-Wuerttemberg
Country [25] 0 0
Germany
State/province [25] 0 0
Bayern
Country [26] 0 0
Germany
State/province [26] 0 0
Niedersachen
Country [27] 0 0
Germany
State/province [27] 0 0
Nordrhein-westfalen
Country [28] 0 0
Germany
State/province [28] 0 0
Schleswig-Holstein
Country [29] 0 0
Italy
State/province [29] 0 0
Torino
Country [30] 0 0
Italy
State/province [30] 0 0
Firenze
Country [31] 0 0
Italy
State/province [31] 0 0
Genova
Country [32] 0 0
Italy
State/province [32] 0 0
Livorno
Country [33] 0 0
Italy
State/province [33] 0 0
Milano
Country [34] 0 0
Italy
State/province [34] 0 0
Perugia
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Cheungcheongbuk-do
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Gyeonggi-do
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Gyeonggi
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Jeollanam-do
Country [39] 0 0
Korea, Republic of
State/province [39] 0 0
Seoul
Country [40] 0 0
Netherlands
State/province [40] 0 0
Limburg
Country [41] 0 0
Netherlands
State/province [41] 0 0
Noord-Holland
Country [42] 0 0
Netherlands
State/province [42] 0 0
Groningen
Country [43] 0 0
Spain
State/province [43] 0 0
Barcelona
Country [44] 0 0
Spain
State/province [44] 0 0
Madrid
Country [45] 0 0
Spain
State/province [45] 0 0
Málaga
Country [46] 0 0
Spain
State/province [46] 0 0
Sevilla
Country [47] 0 0
Taiwan
State/province [47] 0 0
Taichung
Country [48] 0 0
Taiwan
State/province [48] 0 0
Tainan
Country [49] 0 0
Taiwan
State/province [49] 0 0
Taipei
Country [50] 0 0
United Kingdom
State/province [50] 0 0
England

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Clovis Oncology, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02322281
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02322281