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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)


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Locally Advanced or Metastatic Non-small Cell Lung Cancer.

Thank you

Trial Information

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)


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


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 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.

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), PR >240 msec, or QRS >110
msec

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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Incidence of Grade 3 or 4 AEs and clinical lab abnormalities defined as DLTs (Part 1)

Outcome Time Frame:

Cycle 1 (Days 1-21)

Safety Issue:

Yes

Authority:

United States: Food and Drug Administration

Study ID:

CO-1686-008

NCT ID:

NCT01526928

Start Date:

March 2012

Completion Date:

May 2014

Related Keywords:

  • Locally Advanced or Metastatic Non-small Cell Lung Cancer.
  • 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
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location

Mass General HospitalBoston, Massachusetts  02114
Stanford Cancer InstituteStanford, California  94305
UCLA Health SystemSanta Monica, California  90404
University of Colorado Anschutz Medical CampusAurora, Colorado  80045
Karmanos Cancer Care InstituteDetroit, Michigan  48201