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Trial record 4 of 31 for:    clovis oncology

A Phase 1/2 Study of the Safety and Efficacy of Rociletinib When Administered in Combination With Trametinib in Patients With Activating EGFR Mutation-positive Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)

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ClinicalTrials.gov Identifier: NCT02580708
Recruitment Status : Completed
First Posted : October 20, 2015
Last Update Posted : July 26, 2016
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Clovis Oncology, Inc.

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

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: Rociletinib Drug: Trametinib Phase 1 Phase 2

Detailed Description:

This is a Phase 1/2, open-label, non randomized, multicenter study evaluating the safety and efficacy of rociletinib administered in combination with trametinib.

This study will be conducted in 2 phases:

Phase 1: This will be the dose escalation phase of the study. Phase 1 will determine the MAD or MTD and RP2D of the combination of rociletinib and trametinib, and evaluate its safety and tolerability and PK profile in EGFRm NSCLC patients who have failed at least one prior EGFR TKI.

Phase 2: This will be the dose expansion phase. Phase 2 will evaluate the preliminary efficacy and pharmacodynamics of the combination of rociletinib and trametinib at the RP2D in two subsets of EGFRm NSCLC patients.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of the Safety and Efficacy of Rociletinib When Administered in Combination With Trametinib in Patients With Activating EGFR Mutation-positive Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)
Study Start Date : September 2015
Primary Completion Date : May 2016
Study Completion Date : May 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Trametinib
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Rociletinib and Trametinib Drug: Rociletinib
Other Name: CO-1686
Drug: Trametinib
Other Name: Mekinist



Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events [ Time Frame: Continuously, up to approximately 24 months ]
    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

  2. Objective Response Rate (ORR) [ Time Frame: Every 6 weeks until disease progression, up to approximately 24 months ]
    ORR according to RECIST Version 1.1 as determined by Investigator assessment

  3. Cmax of rociletinib and trametinib at steady state [ Time Frame: Cycle 2 Day 1 to Day 2 ]
  4. Tmax of rociletinib and trametinib at steady state [ Time Frame: Cycle 2 Day 1 to Day 2 ]
  5. AUC of rociletinib and trametinib at steady state [ Time Frame: Cycle 2 Day 1 to Day 2 ]
  6. Cmin of rociletinib and trametinib at steady state [ Time Frame: Cycle 2 Day 1 to Day 2 ]
  7. t1/2 of rociletinib at steady state [ Time Frame: Cycle 2 Day 1 to Day 2 ]

Secondary Outcome Measures :
  1. Duration of Response (DR) According to RECIST Version 1.1 [ Time Frame: Every 6 weeks until disease progression, up to approximately 24 months ]
    DR according to RECIST Version 1.1 as determined by Investigator assessment

  2. Disease Control Rate (DCR) According to RECIST Version 1.1 [ Time Frame: Every 6 weeks until disease progression, up to approximately 24 months ]
    DCR according to RECIST Version 1.1 as determined by Investigator assessment

  3. Progression Free Survival (PFS) According to RECIST Version 1.1 [ Time Frame: Every 6 weeks until disease progression, up to approximately 24 months ]
    PFS according to RECIST Version 1.1 as determined by Investigator assessment

  4. Overall Survival (OS) [ Time Frame: Every 12 weeks until date of death, up to approximately 60 months ]
  5. Longitudinal changes in blood based biomarkers (i.e. mutations in EGFR) in ctDNA [ Time Frame: Biomarker samples will be collected from each subject approximately every 3 weeks, up to approximately 24 months ]
  6. Cmax of rociletinib metabolites at steady state [ Time Frame: Cycle 2 Day 1 to Day 2 ]
  7. Tmax of rociletinib metabolites at steady state [ Time Frame: Cycle 2 Day 1 to Day 2 ]
  8. AUC of rociletinib metabolites at steady state [ Time Frame: Cycle 2 Day 1 to Day 2 ]
  9. Cmin of rociletinib metabolites at steady state [ Time Frame: Cycle 2 Day 1 to Day 2 ]


Information from the National Library of Medicine

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

Inclusion Criteria:

  • 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%

Exclusion Criteria:

  • 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

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 ClinicalTrials.gov identifier (NCT number): NCT02580708


Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, North Carolina
Levine Cancer Institute
Charlotte, North Carolina, United States, 28204
United States, Tennessee
Tennessee Oncology, PLLC - The Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Virginia
Virginia Cancer Specialists
Fairfax, Virginia, United States, 22031
Sponsors and Collaborators
Clovis Oncology, Inc.
Novartis Pharmaceuticals
Investigators
Study Director: Paula O'Connor, MD Clovis Oncology

Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02580708     History of Changes
Other Study ID Numbers: CO-1686-033
First Posted: October 20, 2015    Key Record Dates
Last Update Posted: July 26, 2016
Last Verified: July 2016

Additional relevant MeSH terms:
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Bronchial Neoplasms
Carcinoma, Non-Small-Cell Lung
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Trametinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action