Study to Evaluate Safety, Pharmacokinetics, and Efficacy of Rociletinib (CO-1686) in Previously Treated Mutant Epidermal Growth Factor Receptor (EGFR) in Non-Small Cell Lung Cancer (NSCLC) Patients
Rociletinib 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 rociletinib; to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of oral rociletinib; to assess the safety and efficacy of rociletinib in previously treated NSCLC patients known to have the T790M EGFR mutation.
Locally Advanced or Metastatic Non-small Cell Lung Cancer.
|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 Rociletinib in Patients With Previously Treated Mutant EGFR Non-Small Cell Lung Cancer (NSCLC)|
- 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 ]
- 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 rociletinib at Cycle 1 Day 1 and Cycle 1 Day 15 (subset of patients); rociletinib metabolite profiling in Day 15 plasma samples (subset of patients); rociletinib 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 ]
|Study Start Date:||March 2012|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
Oral Rociletinib monotherapy
Phase 1: Rociletinib will be administered in escalating dosages in a period of 21-day cycles
Phase 2: Rociletinib will be administered daily
Other Name: CO-1686
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. Rociletinib may provide an effective therapy for a patient population with few alternative treatment options. Nonclinical data demonstrate that rociletinib inhibits T790M. It is anticipated that rociletinib 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 rociletinib 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01526928
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