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Trial record 1 of 1 for:    NCT02864992
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Tepotinib Phase II in NSCLC Harbouring MET Exon 14 (METex14) Skipping Alterations (VISION)

This study is currently recruiting participants.
Verified November 2017 by EMD Serono ( EMD Serono Research & Development Institute, Inc. )
Sponsor:
ClinicalTrials.gov Identifier:
NCT02864992
First Posted: August 12, 2016
Last Update Posted: November 27, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Merck KGaA
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )
  Purpose
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.

Condition Intervention Phase
Advanced (Stage IIIB/IV) Non-small Cell Lung Cancer With MET Exon 14 (METex14) Skipping Alterations Drug: tepotinib Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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 (VISION)

Resource links provided by NLM:


Further study details as provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]
  • Number of subjects with markedly abnormal clinical laboratory tests (hematology and coagulation, biochemistry and urinalysis). [ Time Frame: Baseline up to 20 months ]

Estimated Enrollment: 120
Actual Study Start Date: September 13, 2016
Estimated Study Completion Date: December 31, 2019
Estimated Primary Completion Date: June 30, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: tepotinib Drug: tepotinib
Subjects receive 500 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.

  Eligibility

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.


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

Inclusion Criteria:

  • Histologically confirmed advanced (Stage IIIB/IV) NSCLC (all histologies including squamous and sarcomatoid)
  • Treatment naive patients in first-line or pre-treated patients with no more than 2 lines of prior therapy
  • METex14 skipping alterations, as determined by the central laboratory (plasma and/or tumor biopsy sample)
  • 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, if the age of majority is > 18 years of age); [i.e. >= 20 years of age in Japan])
  • Measurable disease in accordance with RECIST version 1.1
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
  • A female subjects 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 as defined in Appendix VIII OR
  • A woman of childbearing potential who agrees to use a highly effective contraception (i.e., methods with a failure rate of less than 1 % per year) as detailed in in Appendix VII of this protocol 2 weeks before start of first dose of study treatment, during the treatment period and for at least 4 weeks after the last dose of study treatment. Women of childbearing potential must have a negative pregnancy test (β-HCG test in serum) prior to enrollment.
  • A male subject must agree to use and to have their female partners of childbearing potential to use a highly effective contraception (i.e., methods with a failure rate of less than 1 % per year) as detailed in Appendix VII of this protocol from the first dose of study treatment, during the treatment period and for at least 3 months after the last dose of study treatment and refrain from donating sperm during this period. Male subjects should always use a barrier method such as condom concomitantly.

Exclusion Criteria:

  • Subjects with characterized Epidermal Growth Factor Receptor (EGFR) activating mutations that predict sensitivity to anti-EGFR-therapy, including, but not limited to exon 19 deletions and exon 21 alterations
  • Subjects with characterized Anaplastic Lymphoma Kinase (ALK) rearrangements that predict sensitivity to anti-ALK therapy
  • Active brain metastases (defined as neurologically stable for less than (<) 4 weeks and/or symptomatic and/or requiring treatment with steroids and/or leptomeningeal disease) Subjects must have completed any prior treatment for brain metastases >= 4 weeks prior to start of therapy (>= 2 weeks for stereotactic radiosurgery/gamma knife). Subjects who are neurologically stable on symptomatic therapy with anticonvulsants with low drug interaction risk or whose steroids are being tapered are eligible. Asymptomatic untreated brain metastases less than or equal to (<=) 1 cm of longest diameter are eligible
  • 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 measureable lesion
  • Inadequate hematological, liver, renal, cardiac function
  • Prior treatment with other agents targeting the HGF/c-Met pathway
  • 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
  Contacts and Locations
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): NCT02864992


Contacts
Contact: US Medical Information 888-275-7376
Contact: Merck KGaA Communication Center +49 6151 72 5200 service@merckgroup.com

  Show 92 Study Locations
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA
Investigators
Study Director: Medical Responsible EMD Serono Research & Development Institute, Inc, a business of Merck KGaA, Darmstadt, Germany
  More Information

Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT02864992     History of Changes
Other Study ID Numbers: MS200095-0022
2015-005696-24 ( EudraCT Number )
First Submitted: July 29, 2016
First Posted: August 12, 2016
Last Update Posted: November 27, 2017
Last Verified: November 2017

Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
lung
neoplasm
cancer
tumor
adenocarcinoma
MET exon 14
METex14
pulmonary
stage III
stage IV
c-Met
cMET
NSCLC
advanced non-small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms