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Tepotinib Phase II in Non-small Cell Lung Cancer (NSCLC) Harboring MET Alterations (VISION)

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ClinicalTrials.gov Identifier: NCT02864992
Recruitment Status : Recruiting
First Posted : August 12, 2016
Last Update Posted : June 28, 2019
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Tracking Information
First Submitted Date  ICMJE July 29, 2016
First Posted Date  ICMJE August 12, 2016
Last Update Posted Date June 28, 2019
Actual Study Start Date  ICMJE September 13, 2016
Estimated Primary Completion Date June 25, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 9, 2016)
Objective response as assessed by independent review committee [ Time Frame: Baseline up to 20 months ]
Objective response will be determined according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and as adjudicated by an Independent review committee. Objective response is defined as either a confirmed complete response (CR) or partial response (PR) from first administration of trial treatment to first observation of progressive disease (PD). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02864992 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2018)
  • Objective response assessed as per Investigator [ Time Frame: Baseline up to 20 months ]
    Objective response will be determined according to RECIST 1.1 and as per investigator's discretion. Objective response is defined as either a confirmed complete response (CR) or partial response (PR) from first administration of trial treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
  • Duration of response as assessed by independent review committee [ Time Frame: Baseline until PD/ death within 84 days of last tumor assessment; assessed up to 20 months ]
    Duration of response according to RECIST 1.1 and as adjudicated by an Independent review committee is the time from when the CR/PR (whichever is first) criteria are first met until progression of disease (PD) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
  • Duration of response as assessed by investigator [ Time Frame: Baseline until PD/ death within 84 days of last tumor assessment; assessed up to 20 months ]
    Duration of response according to RECIST 1.1 and as per investigator's discretion is the time from when the CR/PR (whichever is first) criteria are first met until progression of disease (PD) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
  • Objective disease control as assessed by independent review committee [ Time Frame: Baseline up to 20 months ]
    Objective disease control will be determined according to RECIST 1.1 and as adjudicated by an Independent review committee. Objective disease control is defined as either a confirmed CR or PR, or stable disease (SD) lasting at least 12 weeks (84 days) as assessed by independent review committee. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
  • Objective disease control as assessed by investigator [ Time Frame: Baseline up to 20 months ]
    Objective disease control will be determined according to RECIST 1.1 and as per investigator's discretion. Objective disease control is defined as either a confirmed CR or PR, or stable disease (SD) lasting at least 12 weeks (84 days) as assessed by investigator. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
  • Progression free survival as assessed by independent review committee [ Time Frame: Baseline until PD or death within 84 days of last tumor assessment; assessed up to 20 months ]
    Progression free survival as assessed by independent review committee is defined as the time (in months) from the first administration of trial treatment to the date of the first documentation of PD (based on independent review) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
  • Progression free survival as assessed by investigator [ Time Frame: Baseline until PD or death within 84 days of last tumor assessment; assessed up to 20 months ]
    Progression free survival as assessed by investigator is defined as the time (in months) from the first administration of trial treatment to the date of the first documentation of PD (as assessed by investigator) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
  • Overall survival [ Time Frame: Baseline until death, assessed up to 20 months ]
    Overall survival is defined as the time (in months) from first trial treatment administration to the date of death.
  • Occurrence of Treatment emergent adverse event (TEAEs) and deaths [ Time Frame: From the first dose of study drug administration until 33 days after the last dose of study drug administration, assessed up to 20 Months ]
    This outcome measure will be presented as the percentage of subjects with any (serious) adverse event (AE). Percentages are calculated using total number of subjects per treatment cohort as the denominator.
  • Percentage of subjects with of markedly abnormal clinical laboratory tests, vital signs, Electrocardiogram (ECG) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) [ Time Frame: Baseline up to 20 months ]
    This outcome measure will be presented as the percentage of subjects with markedly abnormal vital sign measurements. Percentages are calculated using total number of subjects per treatment cohort as the denominator. Abnormalities in clinical laboratory tests will be measured as hematology and coagulation, biochemistry and urinalysis. Abnormalities in Systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, body temperature as a part of vital signs; electrocardiogram (ECG) wave, body weight, and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), and clinical laboratory tests (hematology and coagulation, biochemistry and urinalysis) will be assessed.
  • European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [ Time Frame: Baseline up to 20 months ]
  • European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) [ Time Frame: Baseline up to 20 months ]
  • EuroQol Five Dimension Five Level Scale (EQ5D5L) [ Time Frame: Baseline up to 20 months ]
  • Maximum Plasma concentration (Cmax) of drug [ Time Frame: pre-dose, at 1.5 hours post-dose and at 4 hours post-dose on Cycle 1, Day 1 and on Cycle 2, Day 1 ]
  • Trough plasma concentration (Ctrough) of drug [ Time Frame: pre-dose, at 1.5 hours post-dose and at 4 hours post-dose on Cycle 1, Day 1 and on Cycle 2, Day 1 ]
  • Number of subjects with markedly abnormal clinical laboratory tests (hematology and coagulation, biochemistry and urinalysis). [ Time Frame: Baseline up to 20 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2016)
  • Objective response assessed as per Investigator [ Time Frame: Baseline up to 20 months ]
    Objective response will be determined according to RECIST 1.1 and as per investigator's discretion. Objective response is defined as either a confirmed complete response (CR) or partial response (PR) from first administration of trial treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
  • Duration of response as assessed by independent review committee [ Time Frame: Baseline until PD/ death within 84 days of last tumor assessment; assessed up to 20 months ]
    Duration of response according to RECIST 1.1 and as adjudicated by an Independent review committee is the time from when the CR/PR (whichever is first) criteria are first met until progression of disease (PD) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
  • Duration of response as assessed by investigator [ Time Frame: Baseline until PD/ death within 84 days of last tumor assessment; assessed up to 20 months ]
    Duration of response according to RECIST 1.1 and as per investigator's discretion is the time from when the CR/PR (whichever is first) criteria are first met until progression of disease (PD) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
  • Objective disease control as assessed by independent review committee [ Time Frame: Baseline up to 20 months ]
    Objective disease control will be determined according to RECIST 1.1 and as adjudicated by an Independent review committee. Objective disease control is defined as either a confirmed CR or PR, or stable disease (SD) lasting at least 12 weeks (84 days) as assessed by independent review committee. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
  • Objective disease control as assessed by investigator [ Time Frame: Baseline up to 20 months ]
    Objective disease control will be determined according to RECIST 1.1 and as per investigator's discretion. Objective disease control is defined as either a confirmed CR or PR, or stable disease (SD) lasting at least 12 weeks (84 days) as assessed by investigator. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
  • Progression free survival as assessed by independent review committee [ Time Frame: Baseline until PD or death within 84 days of last tumor assessment; assessed up to 20 months ]
    Progression free survival as assessed by independent review committee is defined as the time (in months) from the first administration of trial treatment to the date of the first documentation of PD (based on independent review) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
  • Progression free survival as assessed by investigator [ Time Frame: Baseline until PD or death within 84 days of last tumor assessment; assessed up to 20 months ]
    Progression free survival as assessed by investigator is defined as the time (in months) from the first administration of trial treatment to the date of the first documentation of PD (as assessed by investigator) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
  • Overall survival [ Time Frame: Baseline until death, assessed up to 20 months ]
    Overall survival is defined as the time (in months) from first trial treatment administration to the date of death.
  • Occurrence of Treatment emergent adverse event (TEAEs) and deaths [ Time Frame: From the first dose of study drug administration until 33 days after the last dose of study drug administration, assessed up to 20 Months ]
    This outcome measure will be presented as the percentage of subjects with any (serious) adverse event (AE). Percentages are calculated using total number of subjects per treatment cohort as the denominator.
  • Percentage of subjects with of markedly abnormal clinical laboratory tests (hematology and coagulation, biochemistry and urinalysis), vital signs, Electrocardiogram (ECG), and Eastern Cooperative Oncology Group Performance Status (ECOG PS) [ Time Frame: Baseline up to 20 months ]
    This outcome measure will be presented as the percentage of subjects with markedly abnormal vital sign measurements. Percentages are calculated using total number of subjects per treatment cohort as the denominator. Abnormalities in Systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, body temperature as a part of vital signs; electrocardiogram (ECG) wave, body weight, and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), and clinical laboratory tests (hematology and coagulation, biochemistry and urinalysis) will be assessed.
  • European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [ Time Frame: Baseline up to 20 months ]
  • European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) [ Time Frame: Baseline up to 20 months ]
  • EuroQol Five Dimension Five Level Scale (EQ5D5L [ Time Frame: Baseline up to 20 months ]
  • Maximum Plasma concentration (Cmax) of drug [ Time Frame: pre-dose, at 1.5 hours post-dose and at 4 hours post-dose on Cycle 1, Day 1 and on Cycle 2, Day 1 ]
  • Trough plasma concentration (Ctrough) of drug [ Time Frame: pre-dose, at 1.5 hours post-dose and at 4 hours post-dose on Cycle 1, Day 1 and on Cycle 2, Day 1 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tepotinib Phase II in Non-small Cell Lung Cancer (NSCLC) Harboring MET Alterations
Official Title  ICMJE A Phase II, Single-arm Trial to Investigate Tepotinib in Advanced ( Stage IIIB/IV) Non-small Cell Lung Cancer With MET-exon-14 (METex14) Skipping Alterations or MET Amplification (VISION)
Brief Summary This study will look at how effective the study drug (tepotinib) is at stopping the growth and spread of lung cancer. This study will also measure a number of other things including safety of the study drug and the side effects, how body processes the study drug, or how the study drug affects your quality of life. The study also has an optional pharmacogenetic research part. Pharmacogenetic research is an important way to try to understand the role of genetics in human disease and how genes impact the effectiveness of drugs, because differences in genes can change the way a person responds to a particular drug.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced (Stage IIIB/IV) Non-small Cell Lung Cancer With MET Exon 14 (METex14) Skipping Alterations or MET Amplification
Intervention  ICMJE Drug: Tepotinib
Subjects will receive 500 milligram (mg) of tepotinib once daily in cycles of 21-day duration until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.
Study Arms  ICMJE Experimental: Tepotinib
Intervention: Drug: Tepotinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 12, 2018)
120
Original Estimated Enrollment  ICMJE
 (submitted: August 9, 2016)
60
Estimated Study Completion Date  ICMJE December 31, 2019
Estimated Primary Completion Date June 25, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed, written informed consent by subject or legal representative prior to any trial-specific screening procedure
  • Male or female, greater than or equal to (>=) 18 years of age (or having reached the age of majority according to local laws and regulations
  • Measurable disease in accordance with RECIST version 1.1
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
  • A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
  • Not a woman of childbearing potential OR
  • A woman of childbearing potential who agrees to use a highly effective contraception
  • A male subject must agree to use and to have their female partners of childbearing potential to use a highly effective contraception
  • Histologically confirmed advanced (Stage IIIB/IV) Non-small Cell Lung Cancer NSCLC (all histologies including squamous and sarcomatoid)
  • Treatment naïve patients in first-line or pretreated patients with no more than 2 lines of prior therapy
  • Subjects with MET alterations, namely METex14 skipping alterations in plasma and/or tissue, or MET amplification only in plasma and/or tumor biopsy samplet

Exclusion Criteria:

  • Subjects with characterized Epidermal Growth Factor Receptor (EGFR) activating mutations that predict sensitivity to anti-EGFR-therapy
  • Subjects with characterized Anaplastic Lymphoma Kinase (ALK) rearrangements that predict sensitivity to anti-ALK therapy
  • Active brain metastases
  • Any unresolved toxicity Grade 2 or more according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) from previous anticancer therapy
  • Need for transfusion within 14 days prior to the first dose of trial treatment
  • Prior chemotherapy, biological therapy, radiation therapy, hormonal therapy for anti-cancer purposes, targeted therapy, or other investigational anticancer therapy (not including palliative radiotherapy at focal sites) within 21 days prior to the first dose of trial treatment;
  • Subjects who have brain metastasis as the only measurable lesion
  • Inadequate hematological, liver, renal, cardiac function
  • Prior treatment with other agents targeting the Hepatocyte Growth Factor c(HGF/c) -Met pathway
  • Hypertension uncontrolled by standard therapies (not stabilized to < 150/90 mmHg)
  • Past or current history of neoplasm other than Non-small Cell Lung Cancer (NSCLC), except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least 5 years
  • Medical history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the test product
  • Major surgery within 28 days prior to Day 1 of trial treatment
  • Known infection with human immunodeficiency virus, or an active infection with hepatitis B or hepatitis C virus
  • Substance abuse, active infection, or other acute or chronic medical or psychiatric condition or laboratory abnormalities that might increase the risk associated with trial participation at the discretion of Investigators
  • Known hypersensitivity to any of the trial treatment ingredients
  • Legal incapacity or limited legal capacity
  • Any other reason that, in the opinion of the Principal Investigator, precludes the subject from participating in the trial
  • Participation in another clinical trial within the past 30 days
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US Medical Information 888-275-7376
Contact: Merck KGaA Communication Center +49 6151 72 5200 service@merckgroup.com
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Italy,   Japan,   Poland,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02864992
Other Study ID Numbers  ICMJE MS200095-0022
2015-005696-24 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party EMD Serono ( EMD Serono Research & Development Institute, Inc. )
Study Sponsor  ICMJE EMD Serono Research & Development Institute, Inc.
Collaborators  ICMJE Merck KGaA, Darmstadt, Germany
Investigators  ICMJE
Study Director: Medical Responsible EMD Serono Research & Development Institute, Inc, a business of Merck KGaA, Darmstadt, Germany
PRS Account EMD Serono
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP