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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01526928
Recruitment Status : Completed
First Posted : February 6, 2012
Last Update Posted : May 13, 2019
Information provided by (Responsible Party):
Clovis Oncology, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Locally Advanced or Metastatic Non Small Cell Lung Cancer Drug: Rociletinib Phase 1 Phase 2

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 (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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 612 participants
Intervention Model: Single Group Assignment
Masking: None (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)
Actual Study Start Date : March 27, 2012
Actual Primary Completion Date : July 3, 2018
Actual Study Completion Date : August 27, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Rociletinib
Oral Rociletinib monotherapy
Drug: Rociletinib

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

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. Incidence of AEs, clinical laboratory abnormalities, and ECG abnormalities [ Time Frame: Cycle 1 Day 1 to End of Treatment ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. Change from baseline in QT/QTc interval [ Time Frame: Cycle 1 Day 1 to End of Treatment ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 rociletinib
  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 rociletinib
  7. Prior treatment with rociletinib 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 rociletinib
  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 rociletinib
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01526928

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Sponsors and Collaborators
Clovis Oncology, Inc.

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Clovis Oncology, Inc. Identifier: NCT01526928     History of Changes
Other Study ID Numbers: CO-1686-008
First Posted: February 6, 2012    Key Record Dates
Last Update Posted: May 13, 2019
Last Verified: April 2019
Keywords provided by Clovis Oncology, Inc.:
locally advanced
non-small cell lung cancer
epidermal growth factor receptor
EGFR-directed therapy
irreversible EGFR inhibitor
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action