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. (see Contacts and Locations)
Verified September 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: September 10, 2014
Last verified: September 2014
  Purpose

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.


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:
  • Objective Response Rate (ORR) and duration of response per RECIST Version 1.1 by investigator assessment [ Time Frame: Cycle 1 Day 1 to End of Treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective Response Rate (ORR), duration of response and progression-free survival (PFS) per RECIST Version 1.1 as determined by IRR [ Time Frame: Cycle 1 Day 1 to End of Treatment / End of Follow-up ] [ Designated as safety issue: No ]
  • Incidence of AEs, clinical laboratory abnormalities, and ECG abnormalities [ Time Frame: Cycle 1 Day 1 to End of Treatment ] [ Designated as safety issue: Yes ]
  • Overall survival (OR), disease control rate (DCR), and progression-free survival (PFS) per RECIST Version 1.1 as determined by investigator assessment [ Time Frame: Cycle 1 Day 1 to End of Treatment / End of Follow-up ] [ Designated as safety issue: No ]
  • Plasma PK parameters for CO-1686 at Cycle 1 Day 1 and Cycle 1 Day 15 (subset of patients); CO-1686 metabolite profiling in Day 15 plasma samples (subset of patients); CO-1686 based on sparse sampling of all patients [ Time Frame: Cycle 1 Day 1 to End of Treatment ] [ Designated as safety issue: No ]
  • Change from baseline in patient reported outcomes using the Dermatology Life Quality Index, the EORT QLQ - LC13, and the EORT QLQ-C30 [ Time Frame: Cycle 1 Day 1 to End of Treatment ] [ Designated as safety issue: No ]
  • Change from baseline in QT/QTc interval [ Time Frame: Cycle 1 Day 1 to End of Treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 605
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

Phase 1: CO-1686 will be administered in escalating dosages in a period of 21-day cycles

Phase 2: CO-1686 will be administered daily at 500mg BID, 625mg BID, or 750mg BID.


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 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01526928

Contacts
Contact: Clovis Oncology Trial Navigation Service 1-855-262-3040 (USA) clovistrials@emergingmed.com
Contact: Clovis Oncology Trial Navigation Service 1-303-625-5160 (ex-USA) clovistrials@emergingmed.com

  Show 22 Study Locations
Sponsors and Collaborators
Clovis Oncology, Inc.
  More Information

Additional 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: September 10, 2014
Health Authority: United States: Food and Drug Administration
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Australia: Department of Health and Ageing Therapeutic Goods 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:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014