NCT01526928

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

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)

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 612 (actual)
• Sponsor: Clovis Oncology, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

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. 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: Dose-escalation Period with 21-day cycles; optional Treatment Extension Period starting on Day 22 Phase 2: 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 or Cohort C - Patients with discordance between local (T790M positive) and central (T790M negative) T790M results, or had no central test result due to inadequacy of the tissue specimen and known to be T790M positive by local test

Conditions

• Locally Advanced or Metastatic Non Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Rociletinib	Phase 1: Rociletinib \<900 mg BID FB will be administered in escalating dosages in a period of 21-day cycles
DRUG	Rociletinib	Phase 1: Rociletinib 900 mg BID FB will be administered in escalating dosages in a period of 21-day cycles
DRUG	Rociletinib	Phase 1: Rociletinib 500 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles Phase 2: Rociletinib 500 mg BID HBr will be administered daily
DRUG	Rociletinib	Phase 1: Rociletinib 625 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles Phase 2: Rociletinib 625 mg BID HBr will be administered daily
DRUG	Rociletinib	Phase 1: Rociletinib 750 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles Phase 2: Rociletinib 750 mg BID HBr will be administered daily
DRUG	Rociletinib	Phase 1: Rociletinib 1000 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles Phase 2: Rociletinib 1000 mg BID HBr will be administered daily

Timeline

• Start date: 2012-03-27
• Primary completion: 2018-07-03
• Completion: 2018-08-27
• First posted: 2012-02-06
• Last updated: 2020-08-04
• Results posted: 2020-01-06

Locations

49 sites across 4 countries: United States, Australia, France, Poland