Clinical trial NCT02147990: Multicenter Study of Rociletinib Administered to Patients With Previously Treated Mutant EGFR Non-small Cell Lung Cancer
Official 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
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
Lead sponsor: Clovis Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2014-05-28
Enrollment: 318
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: This is a Phase 2, single arm, open-label, dual cohort, multicenter study evaluating the safety and efficacy of rociletinib administered orally to patients with previously treated mutant EGFR NSCLC.

Patients will be enrolled into 2 cohorts. Cohort A will enroll approximately 125 eligible patients who are centrally confirmed T790M-positive. Cohort B will be a continuation of the study and will enroll up to approximately 100 eligible patients who will be either centrally confirmed T790M-positive or T790M-negative.

All patients (for Cohort A and B) should have experienced disease progression while on treatment with the first single-agent EGFR-directed TKI (EGFR-TKI) for advanced/metastatic NSCLC. One line of chemotherapy prior to the EGFR-TKI treatment is permissible.

The study (Cohorts A and B) will consist of a screening phase to establish study eligibility and document baseline measurements, an open-label treatment phase, in which the patient will receive rociletinib to ascertain safety and efficacy until disease progression as defined by RECIST Version 1.1, clinical tumor progression, or unacceptable toxicity as assessed by the investigator. For patients with clinical progression, radiographic assessment should be performed to document evidence of radiographic progression.

Eligibility 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

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

Primary outcomes:
measure: Objective Response Rate (ORR) According to RECIST Version 1.1 as Determined by Investigator Assessment
timeFrame: Cycle 1 Day 1 to End of Treatment, up to approximately 57 months.
Secondary outcomes:
measure: Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment
timeFrame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 54 months
measure: Disease Control Rate (DCR) by RECIST v1.1 as Determined by Investigator Assessment
timeFrame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 57 months
measure: Progression-free Survival (PFS) in T790M Positive Patients by RECIST v1.1 as Determined by Investigator Assessment
timeFrame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 57 months
measure: Overall Survival (OS) Determined by Investigator Assessment
timeFrame: Cycle 1 Day 1 to date of death, assessed up to 57 months
measure: 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
timeFrame: Baseline (Day 0), Months 5, 10 and EOT
measure: Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI)
timeFrame: Baseline (Day 0), Months 5, 10 and EOT
measure: Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale
timeFrame: Baseline (Day 0), Months 5, 10 and EOT
measure: Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale
timeFrame: Baseline (Day 0), Months 5, 10 and EOT
measure: Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale
timeFrame: Baseline (Day 0), Months 5, 10 and EOT
measure: Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale
timeFrame: Baseline (Day 0), Months 5, 10 and EOT
measure: Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale
timeFrame: Baseline (Day 0), Months 5, 10 and EOT
measure: Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale
timeFrame: Baseline (Day 0), Months 5, 10 and EOT
measure: Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale
timeFrame: Baseline (Day 0), Months 5, 10 and EOT
measure: Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale
timeFrame: Baseline (Day 0), Months 5, 10 and EOT
measure: Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale
timeFrame: Baseline (Day 0), Months 5, 10 and EOT
measure: Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale
timeFrame: Baseline (Day 0), Months 5, 10 and EOT
measure: Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale
timeFrame: Baseline (Day 0), Months 5, 10 and EOT
measure: Population PK (POPPK) and Exposure-Response (ER) Analysis of Rociletinib
timeFrame: Every 4 weeks for approximately 6 months (Day 1 of Cycles 2 to 7 inclusive)
Other outcomes:
Locations:
city: Alhambra
country: United States
facility: UCLA Medical Center
state: California
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Fullerton
country: United States
facility: Saint Jude Heritage Healthcare
state: California
city: La Jolla
country: United States
facility: University of California San Diego Moores Cancer Center
state: California
city: Northridge
country: United States
facility: Northridge Hospital Medical Center
state: California
city: Redondo Beach
country: United States
facility: Cancer Care Associates
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: San Luis Obispo
country: United States
facility: Coastal Integrative Cancer Care
state: California
city: Grand Junction
country: United States
facility: Saint Mary's Regional Cancer Center
state: Colorado
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers, LLP
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Miami
country: United States
facility: Advanced Medical Specialties
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Chicago
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Boston
country: United States
facility: Beth Israel Comprehensive Cancer Center
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, P.A
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Latham
country: United States
facility: New York Oncology Hematology, PC
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Amarillo
country: United States
facility: Texas Oncology P.A.
state: Texas
city: Arlington
country: United States
facility: USO - Texas Oncology P.A.
state: Texas
city: Austin
country: United States
facility: Texas Oncology-Austin Central
state: Texas
city: Beaumont
country: United States
facility: Texas Oncology-Beaumont
state: Texas
city: Bedford
country: United States
facility: Texas Oncology P.A.
state: Texas
city: Dallas
country: United States
facility: Texas Oncology P.A.
state: Texas
city: Flower Mound
country: United States
facility: Texas Oncology P.A.
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Plano
country: United States
facility: Texas Oncology - Plano East
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital, North Star Lodge
state: Washington
city: South Brisbane
country: Australia
facility: Icon Cancer Centre
state: New South Wales
city: Sydney
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Besançon
country: France
facility: Centre Hospitalier Regional Universitaire (CHRU) de Besancon - L'Hopital Jean Minjoz
state: Franche-comte
city: Paris
country: France
facility: Hôpital Tenon
state: Ile-de-france
city: Villejuif
country: France
facility: Institut Gustave Roussy
state: Ile-de-France
city: Saint Herblain cedex
country: France
facility: Institut de Cancérologie de l'Ouest - René Gauducheau
state: PAYS DE LA Loire
city: Pierre Bénité cedex
country: France
facility: Centre Hospitalier Lyon Sud
state: Rhone-alpes
city: Caen
country: France
facility: Centre Hospitalier Universitaire Côte de Nacre
city: Marseille Cedex 20
country: France
facility: Centre Hospitalier Universitaire Hôpital Nord
city: Gauting
country: Germany
facility: Asklepios Fachkliniken München-Gauting
state: Bayern
city: München
country: Germany
facility: Klinikum Innenstadt LMU
state: Bayern
city: Frankfurt am Main
country: Germany
facility: Goethe-Universität Frankfurt am Main
state: Hessen
city: Oldenburg
country: Germany
facility: Pius Hospital Oldenburg
state: Niedersachsen
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn - Zentrum fuer Innere Medizin - Medizinische Klinik und Poliklink III
state: Nordrhein-westfalen
city: Essen
country: Germany
facility: Universitätsklinikum Essen
state: Nordrhein-westfalen
city: Köln
country: Germany
facility: Universitätsklinikum Köln
state: Nordrhein-westfalen
city: Großhansdorf
country: Germany
facility: LungenClinic Großhansdorf GmbH
state: Schleswig-holstein
city: Berlin
country: Germany
facility: Evangelische Lungenklinik Berlin
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Chungju
country: Korea, Republic of
facility: Chungbuk National University Hospital
state: Chungcheongbuk-do
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Gyeonggi-do
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul Saint Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Hospital
state: Noord-holland
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum
city: Seville
country: Spain
facility: Hospital Universitario Virgen del Rocio
state: Sevilla
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Vall d´Hebrón
city: Barcelona
country: Spain
facility: Hospital Universitario Quirón Dexeus
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudoise
state: Vaud
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
state: Taipei CITY
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital Linkou
state: Tao-Yuan
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: Guy's and Saint Thomas NHS Foundation Trust
state: Greater London
city: London
country: United Kingdom
facility: Royal Marsden Hospital
state: Greater London
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Trust
state: Surrey
city: London
country: United Kingdom
facility: University College Hospital
Study officials:
References: