Study to Evaluate Safety, Pharmacokinetics, and Efficacy of Rociletinib (CO-1686) in Previously Treated Mutant Epidermal Growth Factor Receptor (EGFR) in Non-Small Cell Lung Cancer (NSCLC) Patients

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase II, Phase IBiomarker/Laboratory analysis, TreatmentActive18 and overPharmaceutical / IndustryCO-1686-008
NCT01526928

Trial Description

Summary

Rociletinib is a novel, potent, small molecule irreversible tyrosine kinase inhibitor (TKI) that selectively targets mutant forms of the epidermal growth factor receptor (EGFR) while sparing wild-type (WT) EGFR. The purpose of the study is to evaluate the pharmacokinetic (PK) and safety profile of oral rociletinib; to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of oral rociletinib; to assess the safety and efficacy of rociletinib in previously treated NSCLC patients known to have the T790M EGFR mutation.

Further Study Information

Lung cancer remains the most common cancer worldwide with non-small cell lung cancer accounting for 85% of cases. Cytotoxic chemotherapy has been the mainstay of patients with NSCLC; however, survival rates remain low and toxicity is significant. Molecularly targeted therapies have proven to be superior to chemotherapy for NSCLC patients whose tumors have mutations in EGFR. Recent studies have established tyrosine kinase inhibitors (TKIs) as the gold standard for treating EGFR-mutation-positive NCSLC. However, patients on TKIs eventually progress, and in approximately 50% of cases, progression is due to development of an additional mutation called T790M. There are currently no approved therapies for patients who progress on TKIs. Rociletinib may provide an effective therapy for a patient population with few alternative treatment options. Nonclinical data demonstrate that rociletinib inhibits T790M. It is anticipated that rociletinib may promote cell death in tumor cells with the T790M mutation, thus providing possible therapeutic benefit in patients who have developed T790M-mediated resistance to first generation TKIs.

This is a two-part, open-label study of oral rociletinib administered daily in previously treated NSCLC patients who have documented evidence of an activating mutation in the EGFR gene and have failed treatment with an EGFR inhibitor such as erlotinib, gefitinib or afatinib.

This study will include 2 parts:

Phase 1 (completed enrolment): Dose-escalation Period with 21-day cycles; optional Treatment Extension Period starting on Day 22

Phase 2 (currently enrolling): Evaluation of activity and safety in patients with the T790M EGFR mutation who have:

Cohort A - Progressed on EGFR directed therapy (irrespective of the number and order of previous lines of NSCLC therapy) or Cohort B - Progression on the first single agent EGFR directed therapy received and also had no more than one previous line of chemotherapy

Eligibility Criteria

Inclusion Criteria -

All patients must meet the following inclusion criteria:

1. Metastatic or unresectable locally advanced NSCLC

2. Evidence of a tumor with one or more EGFR mutations excluding exon 20 insertion

3. Biopsy of either primary or metastatic tumor tissue within 60 days of dosing

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

5. Minimum age of 18 years

6. Adequate hematological and biological function

7. Written consent on an IRB/IEC-approved Informed Consent Form (ICF) prior to any study-specific evaluation

Phase 2 Cohorts must also meet the following inclusion criteria:

  • Disease progression confirmed by radiologic assessment while on treatment with EGFR- TKI Or
  • Disease progression confirmed by radiologic assessment while on treatment with the first single agent EGFR TKI and
  • Documented evidence of T790M mutation in EGFR following disease progression on the first single agent EGFR TKI.
  • Measureable disease according to RECIST Version 1.1

Exclusion Criteria -

Any of the following criteria will exclude patients from study participation:

1. Documented evidence of an Exon 20 insertion activating mutation in the EGFR gene

2. Active second malignancy

3. Known pre-existing interstitial lung disease

4. Patients with Leptomeningeal carcinomatosis are excluded. Other CNS metastases are only permitted if treated, asymptomatic and stable (not requiring steroids for at least 4 weeks prior to start of study treatment).

5. Treatment with prohibited medications less than or equal to 14 days prior to treatment with rociletinib

6. 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

7. Prior treatment with rociletinib or other drugs that target T790M positive mutant EGFR with sparing of wild type EGFR

8. Certain cardiac abnormalities or history

9. Non-study related surgical procedures less than or equal to 7 days prior to administration of rociletinib

10. Females who are pregnant or breastfeeding

11. Refusal to use adequate contraception for fertile patients (females and males) for 12 weeks after the last dose of rociletinib

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

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

Trial Contact Information

Trial Lead Organizations/Sponsors

Clovis Oncology

    Clovis Oncology Trial Navigation Service
    Ph: 1-855-262-3040 (USA)
    Email: clovistrials@emergingmed.com

    Trial Sites

    U.S.A.

    California
    Duarte

    City of Hope Comprehensive Cancer Center

    Abigail Guinto
    Email: aguinto@coh.org

    Karen Reckamp
    Principal Investigator

    Fountain Valley

    Compassionate Care Research Group, Inc.

    Catherine Etheredge
    Email: cetheredge@compcareresearch.com

    Haresh Jhangiani
    Principal Investigator

    Los Angeles

    Samuel Oschin Cancer Center

    Cindi Martin
    Email: cynthia.martin@cshs.org

    Ronald Natale
    Principal Investigator

    USC/Norris Comprehensive Cancer Center and Hospital

    Carol Jones
    Email: jones_c@med.usc.edu

    Barbara Gitlitz
    Principal Investigator

    Orange

    Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center

    Michele Azada
    Email: mazada@uci.edu

    Sai-Hong Ou
    Principal Investigator

    Sacramento

    University of California Davis Cancer Center

    Steffany Lim
    Email: steffany.lim@ucdmc.ucdavis.edu

    David Gandara
    Principal Investigator

    Santa Monica

    Santa Monica UCLA Medical Center

    Suzanne Nichols
    Email: SNichols@mednet.ucla.edu

    Jonathan Goldman
    Principal Investigator

    Stanford

    Stanford Cancer Center

    Dinah Ferro
    Email: dferro@stanford.edu

    Heather Wakelee
    Principal Investigator

    Whittier

    East Valley Hematology and Oncology Medical Group, Inc.

    Christine Marion
    Email: cmarion@icrinstitute.com

    Raul Mena
    Principal Investigator

    The Oncology Institute of Hope and Innovations

    Kirsten Bettino
    Email: kbettino@airesearch.us

    Merrill Shum
    Principal Investigator

    Colorado
    Aurora

    University of Colorado Anschutz Medical Campus

    Shantel Hobson
    Email: shantel.hobson@ucdenver.edu

    David Camidge
    Principal Investigator

    District of Columbia
    Washington

    Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

    Samantha Greenman
    Email: scg70@georgetown.edu

    Stephen Liu
    Principal Investigator

    Florida
    Miami

    University of Miami Sylvester Comprehensive Cancer Center - Miami

    Michelle Mikhail
    Email: alopezchavez@med.miami.edu

    Ariel Lopez-Chavez
    Principal Investigator

    Orlando

    Florida Hospital Cancer Institute

    Janet Jones
    Email: janet.jones@flhosp.org

    Tarek Mekhail
    Principal Investigator

    Georgia
    Athens

    University Cancer & Blood Center

    Jamie Hodgson
    Email: jhodgson@universitycancer.com

    Petros Nikolinakos
    Principal Investigator

    Illinois
    Chicago

    University of Chicago Medical Center, The Duchossois Center for Advanced Medicine

    Will Trost
    Email: wtrost@medicine.bsd.uchicago.edu

    Ravi Salgia
    Principal Investigator

    Maryland
    Baltimore

    Greenebaum Cancer Center at University of Maryland Medical Center

    Maha Khalil
    Email: mkhalil@umm.edu

    Martin Edelman
    Principal Investigator

    Massachusetts
    Boston

    Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

    Abigail McKeon
    Email: Abigail.McKeon@dfci.harvard.edu

    Geoffrey Oxnard
    Principal Investigator

    Massachusetts General Hospital

    Jennifer Nunes
    Email: jnunes1@partners.org

    Lecia Sequist
    Principal Investigator

    Michigan
    Ann Arbor

    Saint Joseph Mercy Cancer Center

    Shannon Porter
    Email: shannon.porter@stjoeshealth.org

    Philip Stella
    Principal Investigator

    Detroit

    Barbara Ann Karmanos Cancer Institute

    Deborah Hackstock
    Email: hackstod@karmanos.org

    Shirish Gadgeel
    Principal Investigator

    New Jersey
    Morristown

    Regional Cancer Care Associates

    Michelle Mackenzie
    Email: mmackenzie@hoannj.com

    Sarada Gurubhagavatula
    Principal Investigator

    New Brunswick

    Regional Cancer Center

    Serena Schmitz
    Email: sschmitz@regionalcancercare.org

    Phillip Reid
    Principal Investigator

    New York
    Buffalo

    Roswell Park Cancer Institute

    Elongia Farrell
    Email: elongia.farrell@roswellpark.org

    Alex Adjei
    Principal Investigator

    Lake Success

    Monter Cancer Center of the North Shore-LIJ Health System

    Theodore Banakos
    Email: tbanakos@nshs.edu

    Harry Raftopoulos
    Principal Investigator

    New York

    Memorial Sloan-Kettering Cancer Center

    Nicole Bramletta
    Email: bramletn@mskcc.org

    Deidre Phillips
    Email: phillid3@mskcc.org

    Helena Yu
    Principal Investigator

    Ohio
    Cincinnati

    Charles M. Barrett Cancer Center at University Hospital

    Ruth Steele
    Email: steelers@ucmail.uc.edu

    John Morris
    Principal Investigator

    Columbus

    Ohio State University, Comprehensive Cancer Center

    Scott Ketcham
    Email: scott.ketcham@osumc.edu

    Gregory Otterson
    Principal Investigator

    Oklahoma
    Tulsa

    Tulsa Cancer Institute - South Yale

    Jolee Holt
    Email: jolee.holt@tciok.org

    Ali Moussa
    Principal Investigator

    Oregon
    Portland

    Providence CancerCenter Oncology and Hematology Care Clinic-Eastside Portland

    Brenda Fisher
    Email: brenda.fisher@providence.org

    Rachel Sanborn
    Principal Investigator

    Pennsylvania
    Philadelphia

    Perelman Center for Advanced Medicine

    Hope Kushner
    Email: hope.kushner@uphs.upenn.edu

    Corey Langer
    Principal Investigator

    Pittsburgh

    University of Pittsburgh Cancer Institute (UPMC), Div. of Medical Oncology

    Lauren Krastas
    Email: kratsasl@upmc.edu

    Mark Socinski
    Principal Investigator

    Tennessee
    Nashville

    Vanderbilt-Ingram Cancer Center

    Melissa Sindler
    Email: melissa.m.sindler@vanderbilt.edu

    Leora Horn
    Principal Investigator

    Texas
    Dallas

    Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

    Rachael Skelton
    Email: rachael.skelton@utsouthwestern.edu

    Joan Schiller
    Principal Investigator

    Houston

    M. D. Anderson Cancer Center at University of Texas

    Griselda Parra
    Email: gparra1@mdanderson.org

    Vassiliki Papadimitrakopoulou
    Principal Investigator

    Utah
    Salt Lake City

    Huntsman Cancer Institute at University of Utah

    Michelle Thompson
    Email: michelle.thompson@hci.utah.edu

    Wallace Akerley
    Principal Investigator

    Virginia
    Fairfax

    Virginia Cancer Specialists

    Alexis Healey
    Email: alexis.healey@usoncology.com

    Alexander Spira
    Principal Investigator

    Washington
    Seattle

    Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

    Andrew Smith
    Email: andrew.smith@swedish.org

    Howard West
    Principal Investigator

    University Cancer Center at University of Washington Medical Center

    Rebecca Wood
    Email: rwood1@seattlecca.org

    Christina Baik
    Principal Investigator

    Australia

    East Melbourne

    Peter MacCallum Cancer Centre

    Lauren McIntyre
    Email: lauren.mcintyre@petermac.org

    Benjamin Solomon
    Principal Investigator

    New South Wales
    Camperdown

    Chris O'Brien Lifehouse

    Annabel Childs
    Email: annabel.childs@lh.org.au

    Michael Boyer
    Principal Investigator

    France

    Caen Cedex 05

    Centre Regional Francois Baclesse

    Emmanuel Girard
    Email: girae@baclesse.unicancer.fr

    Radj Gervais
    Principal Investigator

    Creteil cedex

    Centre Hospitalier Intercommunal Créteil

    Said Baali-Cherif
    Email: said.baalicherif@chicreteil.fr

    Christos Chouaid
    Principal Investigator

    Grenoble Cedex 9

    Centre Hospitalier Universitaire de Grenoble

    Cécile Glommeau
    Email: cglommeau@chu-grenoble.fr

    Denis Moro-Sibilot
    Principal Investigator

    Lille

    Centre Hospitalier Régional Universitaire de Lille

    Eric Wasielewski
    Email: eric.wasielewski@chru-lille.fr

    Alexis Cortot
    Principal Investigator

    Lyon Cedex 04

    Centre Léon Bérard

    Pauline Linard
    Email: pauline.linard@lyon.unicancer.fr

    Maurice Pérol
    Principal Investigator

    Nice Cedex 2

    Centre Antoine Lacassagne

    Estelle Occelli

    Contact Person
    Email: estelle.occelli@nice.unicancer.fr

    Michel Poudenx
    Principal Investigator

    Villejuif

    Institut Gustave Roussy

    Imane Hamoum
    Email: imane.hamoum@gustaveroussy.fr

    Jean-Charles Soria
    Principal Investigator

    Andrea Varga
    Principal Investigator

    Poland

    Gdansk

    Med University Gdansk

    Anita Zakrzewska
    Email: zakrzewska@gumed.edu.pl

    Rafal Dziadziuszko
    Principal Investigator

    Link to the current ClinicalTrials.gov record.
    NLM Identifier NCT01526928
    ClinicalTrials.gov processed this data on April 09, 2015

    Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.