M8891 First in Human in Solid Tumors (M8891)
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|ClinicalTrials.gov Identifier: NCT03138538|
Recruitment Status : Recruiting
First Posted : May 3, 2017
Last Update Posted : April 7, 2020
|Condition or disease||Intervention/treatment||Phase|
|Advanced Solid Tumors||Drug: M8891||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-label, Phase I Dose Escalation Trial of Methionine Aminopeptidase 2 Inhibitor M8891 in Subjects With Advanced Solid Tumors|
|Actual Study Start Date :||August 8, 2017|
|Estimated Primary Completion Date :||July 9, 2020|
|Estimated Study Completion Date :||July 9, 2020|
Subjects will receive M8891 orally once daily or twice daily at escalated dose levels for consecutive 21-day cycles of continuous treatment until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
- Number of Subjects Experienced Any Dose-Limiting Toxicity (DLT) Over the DLT period [ Time Frame: From Cycle Day 1 up to Cycle 1 Day 21 ]DLTs are defined as any pre-defined set of adverse events (AEs) which are defined in the protocol, observed in the first 21-day treatment cycle and judged to be M8891 related or clinically relevant (excluding events to be related to underlying disease, medical history or concomitant medications/ procedures in the opinion of the safety monitoring committee).
- Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation and Death [ Time Frame: Up to 7 months ]AE is defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE is any untoward medical occurrence that at any dose results in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or considered medically important.
- Number of Subjects With Clinical Significant Changes in Laboratory, Electrocardiogram measures, vital signs, Eastern Cooperative Oncology Group Performance status (ECOG PS) [ Time Frame: Up to 8 months ]Clinical laboratory assessments will include hematology, biochemistry and coagulation parameters. Vital sign assessments will include assessments of heart rate, diastolic blood pressure, systolic blood pressure, weight and temperature, ECG and ECOG PS will also be assessed.
- Maximum Observed Plasma Concentration (Cmax) of M8891 [ Time Frame: Day 1, 2, 8, 15, 16 of Cycle 1; Day 1 of Cycle 2 and Cycle 3 ]Cmax will be obtained directly from the concentration versus time curve.
- Time to Reach Maximum Plasma Concentration (Tmax) of M8891 [ Time Frame: Day 1, 2, 8, 15, 16 of Cycle 1; Day 1 of Cycle 2 and Cycle 3 ]Time to reach the maximum plasma concentration (Tmax) will be obtained directly from the concentration versus time curve.
- Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of M8891 [ Time Frame: Day 1, 2, 8, 15, 16 of Cycle 1; Day 1 of Cycle 2 and Cycle 3 ]Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration is at or above the lower limit of quantification (LLQ). AUC0-t will be to be calculated according to the mixed log-linear trapezoidal rule.
- Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of M8891 [ Time Frame: Day 1, 2, 8, 15, 16 of Cycle 1; Day 1 of Cycle 2 and Cycle 3 ]AUC0-inf will be calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLQ) and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
- Area under the plasma concentration versus time curve within one dosing interval (AUC0-tau) of M8891 [ Time Frame: Day 1, 2, 8, 15, 16 of Cycle 1; Day 1 of Cycle 2 and Cycle 3 ]AUC 0-tau is defined as the area under the concentration-time curve from 0 to dosing interval.
- Apparent Terminal Half-life (t1/2) of M8891 [ Time Frame: Day 1, 2, 8, 15, 16 of Cycle 1; Day 1 of Cycle 2 and Cycle 3 ]Terminal half-life is the time measured for the concentration of drug to decrease by one half.
- Apparent Body Clearance From Plasma Following Extravascular Administration (CL/f) of M8891 [ Time Frame: Day 1, 2, 8, 15, 16 of Cycle 1; Day 1 of Cycle 2 and Cycle 3 ]Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed.
- Apparent Volume of Distribution Following Extravascular Administration of M8891 [ Time Frame: Day 1, 2, 8, 15, 16 of Cycle 1; Day 1 of Cycle 2 and Cycle 3 ]Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
- Apparent Terminal Rate Constant of M8891 [ Time Frame: Day 1, 2, 8, 15, 16 of Cycle 1; Day 1 of Cycle 2 and Cycle 3 ]Apparent Terminal Rate Constant is defined as the rate at which drug is cleared from the body.
- Accumulation ratio for AUCtau (Racc(AUCtau)) of M8891 [ Time Frame: Day 1, 2, 8, 15, 16 of Cycle 1; Day 1 of Cycle 2 and Cycle 3 ]Accumulation ratio will be calculated from AUCtau at steady state and AUCtau after single dosing.
- Accumulation ratio for Cmax (Racc(Cmax))of M8891 [ Time Frame: Day 1, 2, 8, 15, 16 of Cycle 1; Day 1 of Cycle 2 and Cycle 3 ]Accumulation ratio will be calculated from Cmax at steady state and Cmax after single dosing.
- Apparent Body Clearance of Drug Following Extravascular Administration at Steady State (CLss/F) of M8891 [ Time Frame: Day 1, 2, 8, 15, 16 of Cycle 1; Day 1 of Cycle 2 and Cycle 3 ]Clearance (CLss/F) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes at steady state.
- Best Overall Response (BOR) [ Time Frame: Time from date of randomization up to end of the treatment or until disease progression (assessed up to 8 months) ]BOR will be determined according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as assessed by investigators. BOR is defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression. 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 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
- Number of Subjects With Clinical Benefit [ Time Frame: Time from date of randomization up to end of the treatment or until disease progression (assessed up to 8 months) ]Clinical benefit defined as Complete Response [CR], Partial Response [PR] or Stable Disease [SD] for >= 12 weeks. Clinical benefit will be assessed according to RECIST Version 1.1. CR: defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: defined as at least a 30% decrease in sum of longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Progressive disease (PD) :defined as at least a 20% increase in sum of longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions. SD: defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of longest diameter while on study.
- Progression-free survival [ Time Frame: Time from date of randomization until disease progression or death (assessed up to 8 months) ]Progression-free survival time (PFS) is defined as the time from first study drug administration to either first observation of disease progression (as assessed by RECIST v 1.1) or occurrence of death due to any cause, whichever occurs first.
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): NCT03138538
|Contact: US Medical Informationemail@example.com|
|United States, Connecticut|
|Smilow Cancer Hospital - Yale||Recruiting|
|New Haven, Connecticut, United States, 06510|
|United States, Indiana|
|Indiana University Health Hospital||Active, not recruiting|
|Indianapolis, Indiana, United States, 46202|
|United States, Maryland|
|Sidney Kimmel Cancer Center - Johns Hopkins||Recruiting|
|Baltimore, Maryland, United States, 21205-1911|
|United States, Michigan|
|Henry Ford Health System||Recruiting|
|Detroit, Michigan, United States, 48202|
|United States, Nevada|
|Comprehensive Cancer Centers of Nevada||Terminated|
|Las Vegas, Nevada, United States, 89169|
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey||Completed|
|New Brunswick, New Jersey, United States, 08901|
|Study Director:||Medical Responsible||EMD Serono Research & Development Institute, Inc., a business of Merck KGaA, Darmstadt, Germany|