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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02147990




Registration number
NCT02147990
Ethics application status
Date submitted
13/05/2014
Date registered
28/05/2014
Date last updated
12/08/2020

Titles & IDs
Public title
Multicenter Study of Rociletinib Administered to Patients With Previously Treated Mutant EGFR Non-small Cell Lung Cancer
Scientific title
TIGER-2: A Phase 2, Open-label, Multicenter, Safety and Efficacy Study of Oral CO-1686 as 2nd Line EGFR-directed TKI in Patients With Mutant EGFR Non-small Cell Lung Cancer (NSCLC)
Secondary ID [1] 0 0
CO-1686-019 (TIGER-2)
Universal Trial Number (UTN)
Trial acronym
NSCLC
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

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

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

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


Treatment: Drugs: Rociletinib
Rociletinib will be administered to patients orally
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) According to RECIST Version 1.1 as Determined by Investigator Assessment
Timepoint [1] 0 0
Cycle 1 Day 1 to End of Treatment, up to approximately 57 months.
Secondary outcome [1] 0 0
Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment
Timepoint [1] 0 0
From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 54 months
Secondary outcome [2] 0 0
Disease Control Rate (DCR) by RECIST v1.1 as Determined by Investigator Assessment
Timepoint [2] 0 0
From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 57 months
Secondary outcome [3] 0 0
Progression-free Survival (PFS) in T790M Positive Patients by RECIST v1.1 as Determined by Investigator Assessment
Timepoint [3] 0 0
From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 57 months
Secondary outcome [4] 0 0
Overall Survival (OS) Determined by Investigator Assessment
Timepoint [4] 0 0
Cycle 1 Day 1 to date of death, assessed up to 57 months
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Baseline (Day 0), Months 5, 10 and EOT
Secondary outcome [6] 0 0
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI)
Timepoint [6] 0 0
Baseline (Day 0), Months 5, 10 and EOT
Secondary outcome [7] 0 0
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale
Timepoint [7] 0 0
Baseline (Day 0), Months 5, 10 and EOT
Secondary outcome [8] 0 0
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale
Timepoint [8] 0 0
Baseline (Day 0), Months 5, 10 and EOT
Secondary outcome [9] 0 0
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale
Timepoint [9] 0 0
Baseline (Day 0), Months 5, 10 and EOT
Secondary outcome [10] 0 0
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale
Timepoint [10] 0 0
Baseline (Day 0), Months 5, 10 and EOT
Secondary outcome [11] 0 0
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale
Timepoint [11] 0 0
Baseline (Day 0), Months 5, 10 and EOT
Secondary outcome [12] 0 0
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale
Timepoint [12] 0 0
Baseline (Day 0), Months 5, 10 and EOT
Secondary outcome [13] 0 0
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale
Timepoint [13] 0 0
Baseline (Day 0), Months 5, 10 and EOT
Secondary outcome [14] 0 0
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale
Timepoint [14] 0 0
Baseline (Day 0), Months 5, 10 and EOT
Secondary outcome [15] 0 0
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale
Timepoint [15] 0 0
Baseline (Day 0), Months 5, 10 and EOT
Secondary outcome [16] 0 0
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale
Timepoint [16] 0 0
Baseline (Day 0), Months 5, 10 and EOT
Secondary outcome [17] 0 0
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale
Timepoint [17] 0 0
Baseline (Day 0), Months 5, 10 and EOT
Secondary outcome [18] 0 0
Population PK (POPPK) and Exposure-Response (ER) Analysis of Rociletinib
Timepoint [18] 0 0
Every 4 weeks for approximately 6 months (Day 1 of Cycles 2 to 7 inclusive)

Eligibility
Key inclusion criteria
Inclusion Criteria

- 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

- 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

- Females who are pregnant or breastfeeding

- Refusal to use adequate contraception for fertile patients (females and males) while
on treatment and for 12 weeks after the last dose of rociletinib

- Presence of any serious or unstable concomitant systemic disorder incompatible with
the clinical study

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

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
Single group
Other design features
Phase
Phase 2
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
16/06/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/08/2019
Sample size
Target
Accrual to date
Final
318
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Icon Cancer Centre - South Brisbane
Recruitment hospital [2] 0 0
Royal North Shore Hospital - Sydney
Recruitment hospital [3] 0 0
Westmead Hospital - Westmead
Recruitment hospital [4] 0 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
2065 - Sydney
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 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
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
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
Missouri
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
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
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
Virginia
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
France
State/province [17] 0 0
Franche-comte
Country [18] 0 0
France
State/province [18] 0 0
Ile-de-france
Country [19] 0 0
France
State/province [19] 0 0
Ile-de-France
Country [20] 0 0
France
State/province [20] 0 0
PAYS DE LA Loire
Country [21] 0 0
France
State/province [21] 0 0
Rhone-alpes
Country [22] 0 0
France
State/province [22] 0 0
Caen
Country [23] 0 0
France
State/province [23] 0 0
Marseille Cedex 20
Country [24] 0 0
Germany
State/province [24] 0 0
Bayern
Country [25] 0 0
Germany
State/province [25] 0 0
Hessen
Country [26] 0 0
Germany
State/province [26] 0 0
Niedersachsen
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
Germany
State/province [29] 0 0
Berlin
Country [30] 0 0
Hong Kong
State/province [30] 0 0
Hong Kong
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Chungcheongbuk-do
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Gyeonggi-do
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Busan
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Incheon
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Seoul
Country [36] 0 0
Netherlands
State/province [36] 0 0
Noord-holland
Country [37] 0 0
Netherlands
State/province [37] 0 0
Amsterdam
Country [38] 0 0
Spain
State/province [38] 0 0
Sevilla
Country [39] 0 0
Spain
State/province [39] 0 0
Badalona
Country [40] 0 0
Spain
State/province [40] 0 0
Barcelona
Country [41] 0 0
Spain
State/province [41] 0 0
Madrid
Country [42] 0 0
Switzerland
State/province [42] 0 0
Vaud
Country [43] 0 0
Taiwan
State/province [43] 0 0
Taipei CITY
Country [44] 0 0
Taiwan
State/province [44] 0 0
Tao-Yuan
Country [45] 0 0
Taiwan
State/province [45] 0 0
Taichung
Country [46] 0 0
Taiwan
State/province [46] 0 0
Taipei
Country [47] 0 0
United Kingdom
State/province [47] 0 0
England
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Greater London
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Surrey
Country [50] 0 0
United Kingdom
State/province [50] 0 0
London

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 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02147990
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/ct2/show/NCT02147990