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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02544633




Registration number
NCT02544633
Ethics application status
Date submitted
4/09/2015
Date registered
9/09/2015
Date last updated
4/03/2020

Titles & IDs
Public title
Phase 2 Study of MGCD265 in Patients With Non-Small Cell Lung Cancer With Activating Genetic Alterations in MET
Scientific title
Phase 2, Parallel-Arm Study of MGCD265 in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer With Activating Genetic Alterations in Mesenchymal-Epithelial Transition Factor
Secondary ID [1] 0 0
265-109
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MGCD265

Experimental: Arm 1 - MGCD265 in patients with MET activating mutations in tumor tissue

Experimental: Arm 2 - MGCD265 in patients with MET gene amplifications in tumor tissue

Experimental: Arm 3 - MGCD265 in patients with MET activating mutations in blood (circulating tumor DNA)

Experimental: Arm 4 - MGCD265 in patients with MET gene amplifications in blood (circulating tumor DNA)


Treatment: Drugs: MGCD265
MGCD265 is a small molecule multi-targeted receptor tyrosine kinase inhibitor

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate - Objective disease response is defined as the percent of patients documented by investigator assessment to have a confirmed Complete Response (CR) or Partial Response (PR) in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for target and non-target lesions as assessed by CT or MRI. CR is defined as complete disappearance of all target lesions with the exception of nodal disease; PR is defined as >=30% decrease under baseline of the sum of diameters of all target measurable lesions; Stable Disease (SD) is concluded when the response does not qualify for CR, PR or Progression; Progressive Disease (PD) is defined as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions.
Timepoint [1] 0 0
Up to 3 months
Secondary outcome [1] 0 0
Duration of Response - Duration of Response (DR) will be defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of Objective Progression of Disease (PD) or to death due to any cause in the absence of documented PD.
Timepoint [1] 0 0
From date of the first documentation of objective tumor response (CR or PR) to the first documentation of Objective Progression of Disease (PD) or to death due to any cause in the absence of documented PD, assessed up to 24 months.
Secondary outcome [2] 0 0
Progression Free Survival - Progression-free survival (PFS) will be defined as the time from date of first study treatment to first PD or death due to any cause in the absence of documented PD. Per RECIST 1.1, Progressive Disease (PD) is defined as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions.
Timepoint [2] 0 0
The time from date of first study treatment to first PD or death due to any cause in the absence of documented PD, up to 24 months.
Secondary outcome [3] 0 0
1-Year Survival Rate - 1-Year Survival will be defined as the probability of survival at 1 year after the first dose.
Timepoint [3] 0 0
From date of first study treatment to death due to any cause, assessed up to 12 months
Secondary outcome [4] 0 0
Overall Survival - Overall Survival will be defined as the time from date of first study treatment to death due to any cause
Timepoint [4] 0 0
From date of first study treatment to death due to any cause, assessed up to 24 months.
Secondary outcome [5] 0 0
Number of Patients Experiencing Treatment-emergent Adverse Events - Number of patients experiencing treatment-emergent adverse events.
Timepoint [5] 0 0
Date of first dose to 28 days after the last dose, up to an average of 5.1 months on treatment.
Secondary outcome [6] 0 0
Blood Plasma Concentration of MGCD265 - AUC0-6 - Blood samples for PK assessment were to be taken on Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. The number of patients reported for each PK parameter was dependent on the actual number of blood samples collected post-dose.
Timepoint [6] 0 0
Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose.
Secondary outcome [7] 0 0
Blood Plasma Concentration of MGCD265 - Cmax - Blood samples for PK assessment were to be taken on Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. On Cycle 2, samples were collected on Day 1 and Day 15 at pre-dose and at 6 hours post-dose (4-8 hours). Note: Assessment of Cmax and Tmax are limited by the sparse blood sampling schedule post dose (i.e., only 2 blood draws post-dose in Cycle 1 and only 1 sample collected post-dose in Cycle 2). The number of patients reported for each PK parameter was dependent on the actual number of blood samples collected post-dose.
Timepoint [7] 0 0
Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. Cycle 2, Day 1 and Day 15 at pre-dose and at 6 hours post-dose (4-8 hours).
Secondary outcome [8] 0 0
Blood Plasma Concentration of MGCD265 - Ctrough - Blood samples for PK assessment were to be taken on Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. On Cycle 2, samples were collected on Day 1 and Day 15 at pre-dose and at 6 hours post-dose (4-8 hours). The number of patients reported for each PK parameter was dependent on the actual number of blood samples collected post-dose.
Timepoint [8] 0 0
Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. Cycle 2, Day 1 and Day 15 at pre-dose and at 6 hours post-dose (4-8 hours).
Secondary outcome [9] 0 0
Blood Plasma Concentration of MGCD265 - Accumulation Ratio AUC0-6 - Blood samples for PK assessment were to be taken on Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. The number of patients reported for each PK parameter was dependent on the actual number of blood samples collected post-dose. Accumulation Ratio AUC0-6 = AUC0-6 C1D15/ AUC0-6 C1D1.
Timepoint [9] 0 0
Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose.
Secondary outcome [10] 0 0
Blood Plasma Concentration of MGCD265 - Accumulation Ratio Cmax - Blood samples for PK assessment were to be taken on Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. The number of patients reported for each PK parameter was dependent on the actual number of blood samples collected post-dose. Accumulation Ration Cmax = Cmax C1D15/ Cmax C1D1.
Timepoint [10] 0 0
Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose.
Secondary outcome [11] 0 0
Blood Plasma Concentration of MGCD265 - Peak to Trough Ratio - Blood samples for PK assessment were to be taken on Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. The number of patients reported for each PK parameter was dependent on the actual number of blood samples collected post-dose. Peak to trough ratio calculated as C1D15 Cmax/Ctrough.
Timepoint [11] 0 0
Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose.
Secondary outcome [12] 0 0
Blood Plasma Concentration of MGCD265 - Tmax - Blood samples for PK assessment were to be taken on Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. Note: Assessment of Cmax and Tmax are limited by the sparse blood sampling schedule post dose (i.e., only 2 blood draws post-dose in Cycle 1 and only 1 sample collected post-dose in Cycle 2). The number of patients reported for each PK parameter was dependent on the actual number of blood samples collected post-dose.
Timepoint [12] 0 0
Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose.
Secondary outcome [13] 0 0
Assess Correlation Between Selected Tumor Gene Alterations Using Different Analytical Techniques in Tumor Tissue and Circulating Tumor Deoxyribonucleic Acid (ctDNA) - MET Activating Mutations - Only a sub-set of patients had different molecular techniques completed, therefore a correlation analysis was not performed. Patients with positive identification by two different analytical techniques are tabulated for MET Activating Mutations.
Timepoint [13] 0 0
At baseline
Secondary outcome [14] 0 0
Assess Correlation Between Selected Tumor Gene Alterations Using Different Analytical Techniques in Tumor Tissue and Circulating Tumor Deoxyribonucleic Acid (ctDNA) - MET Gene Amplifications - Only a sub-set of patients had different molecular techniques completed, therefore a correlation analysis was not performed. Patients with positive identification by two different analytical techniques are tabulated for MET Gene Amplifications.
Timepoint [14] 0 0
At baseline
Secondary outcome [15] 0 0
Assess Change in Genetic Alteration Status in ctDNA With MGCD265 Treatment Over Time in the Selected Population
Timepoint [15] 0 0
At baseline and at time of confirmation of response to treatment
Secondary outcome [16] 0 0
Blood Plasma Concentration of Soluble MET (sMET) Biomarker - MET Activating Mutations in ctDNA. Change from Baseline - Cycle 2 Day 15 - Pre-Dose Standard Deviation not evaluable
Timepoint [16] 0 0
Cycle 1 and Cycle 2

Eligibility
Key inclusion criteria
- Diagnosis of non-small cell lung cancer

- Metastatic or locally advanced disease

- Prior platinum chemotherapy or immunotherapy

- Test result showing genetic change in MET tumor gene

- At least one tumor that can be measured on a radiographic scan
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior treatment with inhibitor of MET or HGF

- Prior positive test for EGFR mutation or ALK gene rearrangement

- Uncontrolled tumor in the brain

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,TAS,VIC
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Saint George Hospital - Kogarah
Recruitment hospital [3] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment hospital [4] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [5] 0 0
Monash Cancer Centre - Clayton
Recruitment hospital [6] 0 0
Austin Health - Heidelberg
Recruitment hospital [7] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [8] 0 0
Monash Health - Clayton
Recruitment hospital [9] 0 0
The Tweed Hospital - Tweed Heads
Recruitment hospital [10] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [4] 0 0
7000 - Hobart
Recruitment postcode(s) [5] 0 0
3165 - Clayton
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
5042 - Bedford Park
Recruitment postcode(s) [8] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [9] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Iowa
Country [11] 0 0
United States of America
State/province [11] 0 0
Kentucky
Country [12] 0 0
United States of America
State/province [12] 0 0
Louisiana
Country [13] 0 0
United States of America
State/province [13] 0 0
Massachusetts
Country [14] 0 0
United States of America
State/province [14] 0 0
Michigan
Country [15] 0 0
United States of America
State/province [15] 0 0
Minnesota
Country [16] 0 0
United States of America
State/province [16] 0 0
Missouri
Country [17] 0 0
United States of America
State/province [17] 0 0
New Jersey
Country [18] 0 0
United States of America
State/province [18] 0 0
New Mexico
Country [19] 0 0
United States of America
State/province [19] 0 0
New York
Country [20] 0 0
United States of America
State/province [20] 0 0
Ohio
Country [21] 0 0
United States of America
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Pennsylvania
Country [22] 0 0
United States of America
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South Carolina
Country [23] 0 0
United States of America
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Tennessee
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United States of America
State/province [24] 0 0
Texas
Country [25] 0 0
United States of America
State/province [25] 0 0
Washington
Country [26] 0 0
Canada
State/province [26] 0 0
Montréal
Country [27] 0 0
Hungary
State/province [27] 0 0
Komarom-esztergom
Country [28] 0 0
Hungary
State/province [28] 0 0
Budapest
Country [29] 0 0
Italy
State/province [29] 0 0
Firenze
Country [30] 0 0
Italy
State/province [30] 0 0
Lucca
Country [31] 0 0
Italy
State/province [31] 0 0
Milano
Country [32] 0 0
Italy
State/province [32] 0 0
Piacenza
Country [33] 0 0
Italy
State/province [33] 0 0
Ravenna
Country [34] 0 0
Italy
State/province [34] 0 0
Torino
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Chungcheongbuk-do
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Gyeonggi-do
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Daegu
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Seoul
Country [39] 0 0
Poland
State/province [39] 0 0
Pomorskie
Country [40] 0 0
Poland
State/province [40] 0 0
Warminsko-mazurskie
Country [41] 0 0
Poland
State/province [41] 0 0
Wielkopolskie
Country [42] 0 0
Taiwan
State/province [42] 0 0
Tainan CITY
Country [43] 0 0
Taiwan
State/province [43] 0 0
Tainan
Country [44] 0 0
Taiwan
State/province [44] 0 0
Hualien City
Country [45] 0 0
Taiwan
State/province [45] 0 0
Kaohsiung
Country [46] 0 0
Taiwan
State/province [46] 0 0
Taichung
Country [47] 0 0
Taiwan
State/province [47] 0 0
Taipei
Country [48] 0 0
United Kingdom
State/province [48] 0 0
England
Country [49] 0 0
United Kingdom
State/province [49] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Mirati Therapeutics Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
MGCD265 is an orally administered receptor tyrosine kinase inhibitor that targets MET and
other receptors. This study is a Phase 2 trial of MGCD265 in patients with locally advanced,
unresectable or metastatic non-small cell lung cancer (NSCLC) that has activating genetic
changes of the MET gene (mutation or amplification [increase number of gene copies]). Testing
for tumor gene changes can be performed in tumor tissue or blood samples. Patients must have
previously received treatment with chemotherapy. The number of patients to be enrolled will
depend on how many enrolled patients experience tumor size reduction. MGCD265 will be
administered orally, twice daily. The study is designed to evaluate whether the number of
patients experiencing tumor size reduction is substantially higher than would be expected
with other available treatments.
Trial website
https://clinicaltrials.gov/show/NCT02544633
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications