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

This study is currently recruiting participants.
Verified April 2014 by Clovis Oncology, Inc.
Sponsor:
Information provided by (Responsible Party):
Clovis Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT01526928
First received: January 31, 2012
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Locally Advanced or Metastatic Non-small Cell Lung Cancer.
Drug: CO-1686
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open-Label, Safety, Pharmacokinetic and Preliminary Efficacy Study of Oral CO-1686 in Patients With Previously Treated Mutant EGFR Non-Small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by Clovis Oncology, Inc.:

Primary Outcome Measures:
  • Incidence of Grade 3 or 4 AEs and clinical lab abnormalities defined as DLTs (Part 1) [ Time Frame: Cycle 1 (Days 1-21) ] [ Designated as safety issue: Yes ]
  • PK Profile (Part 1) [ Time Frame: Cycle 1 (Days 1, 2, 15 and 16) ] [ Designated as safety issue: No ]
    AUC - area under curve from time zero to time t or infinity; Cmax - max concentration; T max - time to max concentration; T 1/2 - elimination half-life; Kel - elimination rate constant; Vss/F volume of distribution at steady state after nonintravenous administration; Cl/F - total plasma clearance

  • ORR and duration of response per RECIST version 1.1 (Part 2) [ Time Frame: Screening; End of Cycles 2,4,6 (between Days 14-21); Every 3 cycles after Cycle 6 (between Days 14-21); and End of study (patient discontinuation) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PK Profile (fasted and fed) (Part 1) [ Time Frame: Cycle 1 (Day -7 and Day 1) ] [ Designated as safety issue: No ]
    AUC and Cmax

  • Change from baseline in QT/QTc interval (ECG) (Parts 1 and 2) [ Time Frame: Screening, Cycle 1 (Days 1 and 15), Cycles 2+ (Day 1), and End of study (patient discontinuation) ] [ Designated as safety issue: Yes ]
  • Metabolic profile in the Day 15 plasma samples (Part 2) [ Time Frame: Cycle 1 (Day 15) ] [ Designated as safety issue: No ]
  • ORR and duration of response per RECIST version 1.1 (Part 1) [ Time Frame: Screening; End of Cycles 2,4,6 (between Days 14-21); Every 3 cycles after Cycle 6 (between Days 14-21); and End of study (patient discontinuation) ] [ Designated as safety issue: No ]
  • Incidence of AEs, clinical laboratory abnormalities, and ECG abnormalities (Part 2) [ Time Frame: Screening, C1+ (Days 1 and 15), End of Study (patient discontinuation) ] [ Designated as safety issue: Yes ]
  • PFS per RECIST version 1.1 (Part 2) [ Time Frame: Screening; End of Cycles 2,4,6 (between Days 14-21); Every 3 cycles after Cycle 6 (between Days 14-21); and End of study (patient discontinuation) ] [ Designated as safety issue: No ]

Estimated Enrollment: 170
Study Start Date: March 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CO-1686
Oral CO-1686 monotherapy
Drug: CO-1686
Oral capsule or tablet administered with 8 oz water as directed by the treating physician; 21-day cycles of treatment. In Part 1, the starting dose will be 150 mg/day and will be escalated until Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) are established. Patients enrolled in Part 2 will receive RP2D until they discontinue from the study.

Detailed Description:

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01526928

Contacts
Contact: Oncology Clinical Trial Information clinicaltrialinfo@clovisoncology.com

Locations
United States, California
University of California, Irvine Recruiting
Orange, California, United States, 92868
UCLA Health System Recruiting
Santa Monica, California, United States, 90404
Stanford Cancer Institute Recruiting
Stanford, California, United States, 94305
United States, Colorado
University of Colorado Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
United States, Massachusetts
Mass General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
Karmanos Cancer Care Institute Recruiting
Detroit, Michigan, United States, 48201
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37235
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Australia
Peter MacCallum Cancer Centre Recruiting
East Melbourne, Australia
France
Institut Gustave Roussy Recruiting
Villejuif, France, 94805
Poland
Med University Gdansk Recruiting
Gdansk, Poland
Sponsors and Collaborators
Clovis Oncology, Inc.
  More Information

No publications provided

Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT01526928     History of Changes
Other Study ID Numbers: CO-1686-008
Study First Received: January 31, 2012
Last Updated: April 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Clovis Oncology, Inc.:
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

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014