Phase 1/2 Study of the Safety and Efficacy of Rociletinib in Combination With Trametinib in Patients With mEGFR-positive Advanced or Metastatic Non-small Cell Lung Cancer

NCT02580708 | Terminated Phase 1

• 1 other identifier: CO-1686-033
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the safety and anti-tumor effect of rociletinib when administered in combination with trametinib.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (7)

• Incidence of treatment-emergent adverse events

  Treatment emergent adverse events (AEs), laboratory abnormalities and ECG abnormalities in EGFR-mutant NSCLC patients given oral rociletinib in combination with oral trametinib; defining in Phase 1 the recommended combination dose for further evaluation in Phase 2

  Continuously, up to approximately 24 months

• Objective Response Rate (ORR)

  ORR according to RECIST Version 1.1 as determined by Investigator assessment

  Every 6 weeks until disease progression, up to approximately 24 months

• Cmax of rociletinib and trametinib at steady state

  Cycle 2 Day 1 to Day 2

• Tmax of rociletinib and trametinib at steady state

  Cycle 2 Day 1 to Day 2

• AUC of rociletinib and trametinib at steady state

  Cycle 2 Day 1 to Day 2

• Cmin of rociletinib and trametinib at steady state

  Cycle 2 Day 1 to Day 2

• t1/2 of rociletinib at steady state

  Cycle 2 Day 1 to Day 2

Secondary Outcomes (9)

• Duration of Response (DR) According to RECIST Version 1.1

  Every 6 weeks until disease progression, up to approximately 24 months

• Disease Control Rate (DCR) According to RECIST Version 1.1

  Every 6 weeks until disease progression, up to approximately 24 months

• Progression Free Survival (PFS) According to RECIST Version 1.1

  Every 6 weeks until disease progression, up to approximately 24 months

• Overall Survival (OS)

  Every 12 weeks until date of death, up to approximately 60 months

• Longitudinal changes in blood based biomarkers (i.e. mutations in EGFR) in ctDNA

  Biomarker samples will be collected from each subject approximately every 3 weeks, up to approximately 24 months

Study Arms (1)

Rociletinib and Trametinib

EXPERIMENTAL

Drug: Rociletinib; Drug: Trametinib

Interventions

Rociletinib DRUG

Also known as: CO-1686

Rociletinib and Trametinib

Trametinib DRUG

Also known as: Mekinist

Rociletinib and Trametinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF before any study-specific evaluation
• Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with EGFR activating mutation (excluding exon 20 insertion); measurable disease per RECIST 1.1
• Prior treatment with an EGFR TKI; in Phase 2, prior treatment with a T790M-directed EGFR TKI for patients in Group B. Previous chemotherapy is allowed; in Phase 2, immediate prior therapy must be EGFR TKI
• Patient willingness to undergo tumor biopsy at baseline and on treatment (optional for Phase 1; mandatory for Phase 2)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1; life expectancy at least 3 months
• Adequate hematological and biological function; LVEF ≥50%

You may not qualify if:

• Documented evidence in tumor of exon 20 insertion, small cell transformation, or MET amplification
• Leptomeningeal carcinomatosis or other untreated or symptomatic CNS metastases (asymptomatic CNS metastases allowed if clinically stable without requirement for steroids within 2 weeks)
• Known preexisting interstitial lung disease or pneumonitis
• Concurrent use of QT-prolonging medication
• Uncontrolled diabetes (HA1C \> 10%) despite optional therapy
• Cardiac abnormalities:
• Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) \>450 ms
• Inability to measure QT interval on ECG
• Personal or family history of long QT syndrome
• Implantable pacemaker or implantable cardioverter defibrillator
• Resting bradycardia \< 55 beats/min
• Inability to swallow oral study treatment or any gastrointestinal disease or condition that would preclude adequate absorption of study treatment
• Presence of serious or unstable concomitant systemic disorder incompatible with the clinical study (eg, substance abuse; uncontrolled intercurrent illness including active infection; arterial thrombosis; unstable respiratory, hepatic, renal or cardiac disease; and other active malignancy)
• Pregnant or breastfeeding females and male or female patients who refuse to use adequate contraception during the study and for 16 weeks after the last dose of study treatment
• Any contraindication, allergy, or hypersensitivity to rociletinib, trametinib, or excipients

Sponsors & Collaborators

• Clovis Oncology, Inc.: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (4)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Tennessee Oncology, PLLC - The Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

rociletinib; trametinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Paula O'Connor, MD

  Clovis Oncology, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2015
• First Posted: October 20, 2015
• Study Start: September 30, 2015
• Primary Completion: May 5, 2016
• Study Completion: June 27, 2016
• Last Updated: October 2, 2018

Record last verified: 2018-09

Locations

US (4)