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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

The purpose of this study is to characterize safety, PK and preliminary efficacy of CO-1686 in patients with mutant EGFR Non-Small Cell Lung Cancer.

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 first-line EGFR inhibitor such as erlotinib or gefitinib.

This study will include 2 parts:

  • Phase 1: Dose-escalation Period with 21-day cycles; optional Treatment Extension Period starting on Day 22
  • Phase 2: Evaluation of the recommended phase 2 dose in patients with the T790M EGFR mutation

Eligibility Criteria

Inclusion Criteria:

Phase 1 or 2

1. Histologically or cytologically confirmed metastatic or unresectable locally advanced, recurrent NSCLC

2. Documented evidence of any activating mutation in the EGFR determined by either sequencing or PCR-based testing of the tumor tissue using local laboratory technique

3. Have undergone biopsy of either primary or metastatic tumor tissue within 28 days of dosing study drug and have tissue available to send to sponsor lab or are able to undergo a biopsy during screening

4. Life expectancy of at least 3 months

5. ECOG performance status of 0 to 1

6. Age ≥ 18 years

7. Adequate hematological and biological function

8. Written consent on an Institutional Review Board/Independent Ethics Committee-approved Informed Consent Form prior to any study-specific evaluation

Patients enrolling into Phase 1 must also meet the following criteria:

1. Prior treatment with EGFR-directed therapy (eg. erlotinib, gefitinib, neratinib, afatinib, or dacomitinib [PF299804]) Prior chemotherapy, including intervening chemotherapy, is allowed.

  • The washout period for a reversible EGFR inhibitor (erlotinib, gefitinib) is a minimum of 5 days.
  • The washout period for an irreversible EGFR inhibitor (neratinib, afatinib, dacomitinib) is a minimum of 14 days.
  • The washout period for chemotherapy is a minimum of 14 days.
  • Any toxicity related to prior treatment must have resolved to Grade 1 or less.

2. Be willing and able to eat a high-fat breakfast on Day 1 of the study (only applicable to food-effect cohort).

Patients enrolling into Phase 2 Cohort A must also meet the following criteria:

1. Disease progression while on treatment with EGFR-directed therapy (e.g. erlotinib, gefitinib, neratinib, afatinib, or dacomitinib [PF299804]) with no intervening treatment allowed after most recent EGFR-directed therapy. Prior chemotherapy is allowed as long as the most recent treatment was an EGFR-directed therapy.

  • The washout period for a reversible EGFR inhibitor (erlotinib, gefitinib) is a minimum of 5 days.
  • The washout period for an irreversible EGFR inhibitor (neratinib, afatinib, dacomitinib) is a minimum of 14 days.
  • Any toxicity related to prior EGFR inhibitor treatment must have resolved to Grade 1 or less.

2. Documented evidence of T790M mutation in EGFR as determined by PCR-based testing of tumor tissue using sponsor central lab following disease progression on most recent prior EGFR-directed therapy.

3. Measurable disease according to RECIST Version 1.1.

4. Do not qualify for enrolment to Phase 2 Cohort B. Patients meeting the eligibility criteria for Cohort B must be enrolled into Cohort B rather than Cohort A.

Patients enrolling into Phase 2 Cohort B must also meet the following criteria:

1. Disease progression while on continuous treatment with the first single agent EGFR-directed therapy (e.g. erlotinib, gefitinib, neratinib, afatinib, or dacomitinib [PF299804]) within the last 30 days, with no intervening treatment before planned initiation of CO-1686.

  • The washout period for a reversible EGFR inhibitor (erlotinib, gefitinib) is a minimum of 5 days.
  • The washout period for an irreversible EGFR inhibitor (neratinib, afatinib, dacomitinib) is a minimum of 14 days.
  • Any toxicity related to prior EGFR inhibitor treatment must have resolved to Grade 1 or less.

2. Documented evidence of T790M mutation in EGFR as determined by PCR-based testing of tumor tissue using sponsor central lab following disease progression on the first single agent EGFR-directed therapy.

3. Measurable disease according to RECIST Version 1.1.

4. ≤ 1 prior line of chemotherapy

Exclusion Criteria:

1. History of prior malignancy except:

  • Curatively treated non-melanoma skin cancer
  • Curatively treated in-situ cervical cancer
  • Incidental histologic finding of prostate cancer (tumor/node/metastasis [TNM] stage of T1a or T1b)

2. History of interstitial lung disease related to prior EGFR inhibitor therapy

3. Symptomatic brain metastases

4. Treatment with prohibited medications (e.g., concurrent anticancer therapy including other chemotherapy, radiation [except palliative radiation therapy on non-target lesions for patients without progression], hormonal treatment [except corticosteroids and megestrol acetate], or immunotherapy) ≤14 days prior to treatment with CO-1686

5. Prior treatment with CO-1686

6. Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) >450 msec (males) or >470 msec (females)

7. Family history of long QT syndrome

8. Implantable pacemaker or implantable cardioverter defibrillator

9. For phase 1 patients, treatment with any medication known to produce QT prolongation

10. Non-study related surgical procedures ≤14 days prior to administration of CO-1686. In all cases, the patient must be sufficiently recovered and stable before treatment administration.

11. Females who are pregnant or breastfeeding

12. Refusal to use adequate contraception for fertile patients (females and males) for 6 months after the last dose of CO-1686

13. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled psychiatric condition, uncontrolled intercurrent illness including active infection, arterial thrombosis, and symptomatic pulmonary embolism)

14. 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
  Santa Monica
 Santa Monica UCLA Medical Center
  Stanford
 Stanford Cancer Center
Colorado
  Aurora
 University of Colorado Cancer Center at UC Health Sciences Center
Massachusetts
  Boston
 Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
 Massachusetts General Hospital
Michigan
  Detroit
 Barbara Ann Karmanos Cancer Institute
Tennessee
  Nashville
 Vanderbilt University
Texas
  Houston
 M. D. Anderson Cancer Center at University of Texas
Australia
  East Melbourne
 Peter MacCallum Cancer Centre
France
  Villejuif
 Institut Gustave Roussy
Poland
  Gdansk
 Med University Gdansk

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01526928
ClinicalTrials.gov processed this data on April 14, 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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