A Study of RO5185426 in Previously Treated Melanoma Patients With Brain Metastases

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01253564
First received: December 2, 2010
Last updated: July 13, 2015
Last verified: July 2015
  Purpose
This open-label study will assess the safety and efficacy of RO5185426 in previously treated metastatic melanoma patients with brain metastases. Patients will receive RO5185426 at a dose of 960 mg twice daily orally until disease progression or unacceptable toxicity occurs.

Condition Intervention Phase
Malignant Melanoma
Drug: RO5185426
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Pilot Study of RO5185426 in Previously Treated Metastatic Melanoma Patients With Brain Metastases

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Adverse Events (AEs) [ Time Frame: From baseline up to last dose (0.1 to 11.3 months) plus 28 days ] [ Designated as safety issue: No ]
    AE:any unfavorable and unintended sign, symptom, or disease associated with use of study drug, regardless of relation to study drug. Pre-existing conditions that worsened and laboratory or clinical tests that resulted in change in treatment or discontinuation from study drug were reported as AEs. Serious AE: resulted in death, life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect or was medically significant. Grade-1:discomfort but no disruption of normal daily activity. Grade-2:discomfort sufficient to reduce or affect daily activity,no intervention indicated.Grade-3:inability to perform normal daily activity,intervention indicated.Grade-4:immediate threat to life or leading to permanent mental or physical condition that prevented performing normal daily activities.Grade 5: death. Any AE included participants with serious and non-serious AE.


Secondary Outcome Measures:
  • Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Disease Site [ Time Frame: Baseline, Week 4, Week 8 and thereafter every 8th week until progressive disease, unacceptable toxicity, consent withdrawal, death or other reasons deemed by the investigator (up to 16 months) ] [ Designated as safety issue: No ]
    Objective response was assessed by the investigator according to Response Evaluation Criteria in Solid Tumours (RECIST) (Version 1.1). CR was defined as disappearance of all target and non-target lesions and no new lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Best overall response was calculated separately for brain, other sites (extracranial) and whole body. Percentage of participants with 95 percent (%) Clopper-Pearson confidence interval (CI) are reported.

  • Duration of Response by Disease Site [ Time Frame: Baseline, Week 4, Week 8 and thereafter every 8th week until progressive disease or death (up to 16 months) ] [ Designated as safety issue: No ]
    Duration of response was defined as the time interval between the date of the earliest qualifying response and the date of progressive disease (PD) or death, only for those participants whose best overall response was CR or PR. CR and PR were assessed by investigator according to RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. PD was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 millimeter (mm), progression of existing non-target lesions, or presence of new lesions. Duration of response was calculated by Kaplan-Meier estimates separately for brain, other sites (extracranial) and whole body.

  • Time to Response by Disease Site [ Time Frame: Baseline, Week 4, Week 8 and thereafter every 8th week until progressive disease, unacceptable toxicity, consent withdrawal, death or other reasons deemed by the investigator (up to 16 months) ] [ Designated as safety issue: No ]
    Time to response was defined as the interval between the date of first treatment and the date of first documentation of CR or PR (whichever occurred first). CR and PR were assessed by investigator according to RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Time of response was calculated by Kaplan-Meier estimates separately for brain, other sites (extracranial) and whole body.

  • Duration of Stable Disease (SD) by Disease Site [ Time Frame: Baseline, Week 4, Week 8 and thereafter every 8th week until progressive disease, unacceptable toxicity, consent withdrawal, death or other reasons deemed by the investigator (up to 16 months) ] [ Designated as safety issue: No ]
    Duration of SD was defined as the time between the first documented date of SD and date of PD or death from any cause. SD was defined (according to RECIST version 1.1) as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. PD was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Duration of SD was calculated by Kaplan-Meier estimates separately for brain, other sites (extracranial) and whole body.

  • Time to New Lesion by Disease Site [ Time Frame: Baseline, Week 4, Week 8 and thereafter every eighth week until progressive disease, unacceptable toxicity, consent withdrawal, death or other reasons deemed by the investigator (up to 16 months) ] [ Designated as safety issue: No ]
    Time to new lesions was defined as the interval between the date of first treatment and the date of first documentation of new lesions. Time to new lesion was calculated by Kaplan-Meier estimates separately for brain, other sites (extracranial) and whole body.

  • Percentage of Participants With Disease Progression or Death by Disease Site [ Time Frame: Baseline, Week 4, Week 8 and thereafter every 8th week until progressive disease, unacceptable toxicity, consent withdrawal, death or other reasons deemed by the investigator (up to 16 months) ] [ Designated as safety issue: No ]
    Disease progression (according to RECIST version 1.1) was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study or absolute increase and at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Percentage of participants with disease progression by brain, other sites (extracranial) and whole body are reported.

  • Progression Free Survival (PFS) [ Time Frame: Baseline, Week 4, Week 8 and thereafter every eighth week until progressive disease, unacceptable toxicity, consent withdrawal, death or other reasons deemed by the investigator (up to 16 months) ] [ Designated as safety issue: No ]
    PFS was defined as the time interval between the date of the first treatment and the date of progression or death from any cause, whichever occurred first. Disease progression (according to RECIST version 1.1) was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study or absolute increase and at least 5 mm, progression of existing non-target lesions, or presence of new lesions. PFS was calculated by Kaplan-Meier estimates separately for brain, other sites (extracranial) and whole body.

  • Percentage of Participants Who Died [ Time Frame: Baseline up to end of the study and every 3 months during follow-up (up to 16 months) ] [ Designated as safety issue: No ]
    Percentage of participants who died due to any reason are reported.

  • Overall Survival (OS) [ Time Frame: From start of treatment up to end of the study and every 3 months during follow up (up to 16 months) ] [ Designated as safety issue: No ]
    OS was defined as the time from the date of first treatment to the date of death, regardless of the cause of death. Participants who discontinued the study treatment for any reason other than withdrawal of consent were continued to be followed for survival. The end of study occurred when all participants had been followed for a period of 6 months, had died, withdrawn consent or were lost to follow-up, whichever occurred first. OS was calculated by Kaplan-Meier estimates.

  • Percentage of Participants With Improvement in Total Daily Dose of Corticosteroids [ Time Frame: Baseline, every week during the first 8 weeks and every second week thereafter up to last dose (0.1 to 11.3 months) plus 28 days ] [ Designated as safety issue: No ]
    An improvement in corticosteroid dose was defined as a dose reduction of at least 33% of baseline dose for at least 28 days or stopping use completely. Percentage of participants and 95% Clopper-Pearson CI are reported.

  • Percentage of Participants With Improvement in Total Daily Dose of Narcotic Pain Analgesic [ Time Frame: Baseline, every week during the first 8 weeks and every second week thereafter up to last dose (0.1 to 11.3 months) plus 28 days ] [ Designated as safety issue: No ]
    An improvement in narcotic pain analgesics was defined as a dose reduction of at least 33% of baseline dose for at least 28 days or stopping use completely.

  • Percentage of Participants With Improvement in Visual Analog Scale (VAS) Assessment of Pain [ Time Frame: Baseline; Day 1 of Cycles 2-8 (28-day cycle) and at the end of study visit (up to 16 months) ] [ Designated as safety issue: No ]
    VAS is a measure of pain intensity. The participant was asked to mark on a 100 mm line where their pain level was on the day they completed the scale. The beginning of the line represented no pain and the end of the line represented maximum pain. Total score ranged from 0 - 100. Reported values are decrease in VAS of greater than (>) 20 mm or >30 mm from baseline.

  • Percentage of Participants With Improvement in Physician's Assessment of Global Performance Status [ Time Frame: Baseline, Day 1 of every 28-day cycle, at end of study and at the 28-day follow-up visit (up to 16 months) ] [ Designated as safety issue: No ]
    Physician's Assessment of Global Performance Status was assessed on 7 point scale (1- Very much better, 2-Much better, 3-A little better, 4-No change, 5-A little worse, 6-Much worse, 7- Very much worse). An improvement was classed as a difference from baseline of at least -1 point. Percentage of participants with 95% Clopper-Pearson CI were reported for participants with improvement in Physician's Assessment of Global Performance Status at any visit.


Enrollment: 24
Study Start Date: November 2010
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm Drug: RO5185426
960 mg b.i.d. orally

  Eligibility

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

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Metastatic melanoma (Stage IV, American Joint Committee on Cancer) with BRAF mutation (cobas 4800 BRAF V600 Mutation Test)
  • Brain metastases for which surgical resection is not a treatment option
  • Patients must have failed at least one previous treatment for brain metastases
  • Requiring corticosteroids for symptom control
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Exclusion Criteria:

  • Increasing corticosteroid dose during the 7 days prior to study entry
  • Previous malignancy within the past 2 years, except for basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix
  • Concurrent administration of any anticancer therapies other than those administered in the study
  • Clinically significant cardiovascular disease or event within the 6 months prior to first dose of study drug
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01253564

Locations
Switzerland
Lausanne, Switzerland, 1011
Zürich, Switzerland, 8091
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01253564     History of Changes
Other Study ID Numbers: MO25653 
Study First Received: December 2, 2010
Results First Received: July 13, 2015
Last Updated: July 13, 2015
Health Authority: Switzerland: Swissmedic

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on August 23, 2016