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Clinical Trials (PDQ®)

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

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

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

Trial Description

Summary

CO-1686 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 CO-1686; to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of oral CO-1686; to assess the safety and efficacy of CO-1686 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. CO-1686 may provide an effective therapy for a patient population with few alternative treatment options. Nonclinical data demonstrate that CO-1686 inhibits T790M. It is anticipated that CO-1686 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 CO 1686 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. Leptomeningeal carcinomatosis or other untreated or symptomatic central nervous system (CNS) metastases. Patients with asymptomatic CNS metastases, other than leptomeningeal disease, are eligible, provided they have been clinically stable without requiring increase in steroid dose for at least 4 weeks.

5. Treatment with prohibited medications less than or equal to 14 days prior to treatment with CO-1686

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 CO-1686

7. Prior treatment with CO-1686 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 CO-1686

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 CO-1686

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

Oncology Clinical Trial Information
  Email: clinicaltrialinfo@clovisoncology.com

Trial Sites

U.S.A.
California
  Orange
 Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
 Michele Azada
  Email: mazada@uci.edu
  Santa Monica
 Santa Monica UCLA Medical Center
 Suzanne Nichols
  Email: SNichols@mednet.ucla.edu
  Stanford
 Stanford Cancer Center
 Dinah Ferro
  Email: dferro@stanford.edu
Colorado
  Aurora
 University of Colorado Anschutz Medical Campus
 Amy Brown
  Email: amy.m.brown@ucdenver.edu
 Paula Fisk
  Email: paula.fisk@ucdenver.edu
District of Columbia
  Washington
 Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
 Jeanette Crawford
  Email: crawfojg@georgetown.edu
 Sylvia Alarcon Velasco
  Email: sva24@georgetown.edu
Massachusetts
  Boston
 Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
 Tanya Mital
  Email: tanya_mital@dfci.harvard.edu
 Massachusetts General Hospital
 Jennifer Nunes
  Email: jnunes1@partners.org
Michigan
  Detroit
 Barbara Ann Karmanos Cancer Institute
 Deborah Hackstock
  Email: hackstod@karmanos.org
New York
  New York
 Memorial Sloan-Kettering Cancer Center
 Joanne Nicholls
  Email: nichollj@mskcc.org
Ohio
  Columbus
 Ohio State University, Comprehensive Cancer Center
 Scott Ketcham
  Email: scott.ketcham@osumc.edu
Tennessee
  Nashville
 Vanderbilt-Ingram Cancer Center
 Melissa Sindler
  Email: melissa.m.sindler@vanderbilt.edu
Texas
  Houston
 M. D. Anderson Cancer Center at University of Texas
 Griselda Parra
  Email: gparra1@mdanderson.org
Virginia
  Fairfax
 Virginia Cancer Specialists
 Karin Choquette
  Email: karin.choquette@usoncology.com
Australia
  East Melbourne
 Peter MacCallum Cancer Centre
 Lauren McIntyre
  Email: lauren.mcintyre@petermac.org
France
  Villejuif
 Institut Gustave Roussy
 Pargol Zandyazdi
  Email: pargol.zandyazdi@igr.fr
 Imane Hamoum
  Email: imane.hamoum@gustaveroussy.fr
Poland
  Gdansk
 Med University Gdansk
 Anita Zakrzewska
  Email: zakrzewska@gumed.edu.pl

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01526928
ClinicalTrials.gov processed this data on July 10, 2014

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.

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