Brief Summary
The purpose of this study is to characterize the effect of a single dose of 40 mg sapanisertib (MLN0128) on the electrocardiographic QT/QTc interval in participants with advanced solid tumors.
Brief Title
Effect of Sapanisertib (MLN0128) on the QTc Interval in Participants With Advanced Solid Tumors
Detailed Description
The drug being tested in this study is called sapanisertib (MLN0128). Sapanisertib is being tested to determine the effect of a single 40 mg dose on the electrocardiographic measure of the time between the start of the Q wave and the end of the T wave in the electrical cycle of the heart (QT)/rate corrected QT (QTc) interval in patients with advanced solid tumors. This study will look at electrocardiogram (ECG) results before and after a single dose of sapanisertib.
The study will enroll approximately 30 patients. All participants will receive a single 40 mg dose of sapanisertib capsules on Day 1. Participants may continue to receive sapanisertib for up to 1 year at a dose of up to 30 mg once weekly if a clinical benefit is being derived.
This multi-centre trial will be conducted in the United States. The overall time to participate in this study is up to 14 months. Participants will make 6 visits to the clinic and end of study visit 30 to 40 days after last dose of study drug for a follow-up assessment. Participants that continue treatment with sapanisertib will continue to make additional visits to the clinic once or twice every 4 weeks and the end of study visit 30 to 40 days after last dose of study drug for a follow-up assessment.
The study will enroll approximately 30 patients. All participants will receive a single 40 mg dose of sapanisertib capsules on Day 1. Participants may continue to receive sapanisertib for up to 1 year at a dose of up to 30 mg once weekly if a clinical benefit is being derived.
This multi-centre trial will be conducted in the United States. The overall time to participate in this study is up to 14 months. Participants will make 6 visits to the clinic and end of study visit 30 to 40 days after last dose of study drug for a follow-up assessment. Participants that continue treatment with sapanisertib will continue to make additional visits to the clinic once or twice every 4 weeks and the end of study visit 30 to 40 days after last dose of study drug for a follow-up assessment.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Advanced Solid Tumors
Eligibility Criteria
Inclusion Criteria
* Men or women participants 18 years or older.
* Must have a radiographically or clinically evaluable solid tumor Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Female participants who are postmenopausal for at least 1 year before the screening visit, OR are surgically sterile, OR if they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 3 months after the last dose of study drug, OR agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post ovulation methods\] and withdrawal are not acceptable methods of contraception.)
* Male participants, even if surgically sterilized (i.e., status post vasectomy), who agree to practice effective barrier contraception during the entire study treatment period and through 3 months after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post ovulation methods for the female partner\] and withdrawal are not acceptable methods of contraception.)
* Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
* Ability to swallow oral medications, willingness to perform mucositis prophylaxis, and suitable venous access for the study-required blood sampling.
Exclusion Criteria
* Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the screening period.
* Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
* Treatment with any investigational products within 14 days before the first dose of study drug and systemic anticancer therapy within 28 days before the first dose of study drug.
* Untreated brain metastasis or history of leptomeningeal disease or spinal cord compression.
* Tumors with involvement of the mediastinum.
* Failure to recover from the reversible effects of prior anticancer therapies with the exception of alopecia, and after-effects associated with prior tyrosine kinase inhibitor therapy such as hair depigmentation, hypothyroidism, and/or splinter hemorrhage.
* Systemic corticosteroid (inhalers are allowed) within 7 days before the first dose of study drug.
* Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown or other reason that may alter the absorption of Sapanisertib.
* Diagnosis of diabetes mellitus; participants with a history of transient glucose intolerance due to corticosteroid administration may be enrolled if all other inclusion/exclusion criteria are met.
* Significant active cardiovascular or pulmonary disease at study entry
* History of arrhythmia requiring an implantable cardiac defibrillator
* Clinically significant comorbidities such as uncontrolled pulmonary disease, active central nervous system disease, active infection, serious infection within 14 days before the first dose of study drug, or any other condition that could compromise study participation by the participant.
* Men or women participants 18 years or older.
* Must have a radiographically or clinically evaluable solid tumor Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Female participants who are postmenopausal for at least 1 year before the screening visit, OR are surgically sterile, OR if they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 3 months after the last dose of study drug, OR agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post ovulation methods\] and withdrawal are not acceptable methods of contraception.)
* Male participants, even if surgically sterilized (i.e., status post vasectomy), who agree to practice effective barrier contraception during the entire study treatment period and through 3 months after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post ovulation methods for the female partner\] and withdrawal are not acceptable methods of contraception.)
* Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
* Ability to swallow oral medications, willingness to perform mucositis prophylaxis, and suitable venous access for the study-required blood sampling.
Exclusion Criteria
* Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the screening period.
* Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
* Treatment with any investigational products within 14 days before the first dose of study drug and systemic anticancer therapy within 28 days before the first dose of study drug.
* Untreated brain metastasis or history of leptomeningeal disease or spinal cord compression.
* Tumors with involvement of the mediastinum.
* Failure to recover from the reversible effects of prior anticancer therapies with the exception of alopecia, and after-effects associated with prior tyrosine kinase inhibitor therapy such as hair depigmentation, hypothyroidism, and/or splinter hemorrhage.
* Systemic corticosteroid (inhalers are allowed) within 7 days before the first dose of study drug.
* Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown or other reason that may alter the absorption of Sapanisertib.
* Diagnosis of diabetes mellitus; participants with a history of transient glucose intolerance due to corticosteroid administration may be enrolled if all other inclusion/exclusion criteria are met.
* Significant active cardiovascular or pulmonary disease at study entry
* History of arrhythmia requiring an implantable cardiac defibrillator
* Clinically significant comorbidities such as uncontrolled pulmonary disease, active central nervous system disease, active infection, serious infection within 14 days before the first dose of study drug, or any other condition that could compromise study participation by the participant.
Inclusion Criteria
Inclusion Criteria
* Men or women participants 18 years or older.
* Must have a radiographically or clinically evaluable solid tumor Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Female participants who are postmenopausal for at least 1 year before the screening visit, OR are surgically sterile, OR if they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 3 months after the last dose of study drug, OR agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post ovulation methods\] and withdrawal are not acceptable methods of contraception.)
* Male participants, even if surgically sterilized (i.e., status post vasectomy), who agree to practice effective barrier contraception during the entire study treatment period and through 3 months after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post ovulation methods for the female partner\] and withdrawal are not acceptable methods of contraception.)
* Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
* Ability to swallow oral medications, willingness to perform mucositis prophylaxis, and suitable venous access for the study-required blood sampling.
inclusion/
* Men or women participants 18 years or older.
* Must have a radiographically or clinically evaluable solid tumor Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Female participants who are postmenopausal for at least 1 year before the screening visit, OR are surgically sterile, OR if they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 3 months after the last dose of study drug, OR agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post ovulation methods\] and withdrawal are not acceptable methods of contraception.)
* Male participants, even if surgically sterilized (i.e., status post vasectomy), who agree to practice effective barrier contraception during the entire study treatment period and through 3 months after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post ovulation methods for the female partner\] and withdrawal are not acceptable methods of contraception.)
* Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
* Ability to swallow oral medications, willingness to perform mucositis prophylaxis, and suitable venous access for the study-required blood sampling.
inclusion/
Gender
All
Gender Based
false
Keywords
Drug therapy
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02197572
Org Class
Industry
Org Full Name
Calithera Biosciences, Inc
Org Study Id
C31002
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 1 Study to Evaluate the Effect of MLN0128 on the QTc Interval in Patients With Advanced Solid Tumors
Primary Outcomes
Outcome Description
The mean changes of QTcI from time-matched baseline was measured by electrocardiogram (ECG) to evaluate the potential effect of drug on QTc interval duration. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measures mixed effects linear model. A negative change from baseline indicates shortening and a positive change from baseline indicates prolongation of QTcI interval.
Outcome Measure
Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval
Outcome Time Frame
Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose
Secondary Ids
Secondary Id
U1111-1156-4099
Secondary Outcomes
Outcome Description
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent.
Outcome Time Frame
From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months)
Outcome Measure
Number of Participants With Atleast One Adverse Event (AE) and Serious Adverse Event (SAE)
Outcome Description
The laboratory parameters included clinical chemistry, hematology, and urinalysis. Any abnormal change in the laboratory values were assessed by Investigator and reported as AE. An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.
Outcome Time Frame
From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months)
Outcome Measure
Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Reported as AE
Outcome Description
Vital sign measurements included blood pressure (diastolic and systolic), heart rate, and temperature. Any abnormal change in the vital sign values were assessed by Investigator and reported as AE. An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.
Outcome Time Frame
From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months)
Outcome Measure
Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Reported as AE
Outcome Description
The mean changes of QTcB from time-matched baseline was measured by ECG to evaluate the potential effect of drug on QTc interval duration. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measures mixed effects linear model. A negative change from baseline indicates shortening and a positive change from baseline indicates prolongation of QTcB interval.
Outcome Time Frame
Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose
Outcome Measure
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB)
Outcome Description
The mean changes of QTcF from time-matched baseline was measured by ECG to evaluate the potential effect of drug on QTc interval duration. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measures mixed effects linear model. A negative change from baseline indicates shortening and a positive change from baseline indicates prolongation of QTcF interval.
Outcome Time Frame
Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose
Outcome Measure
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF)
Outcome Description
QRS interval is defined as the time between the start of the Q wave and end of the S wave on ECG. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measures mixed effects linear model. A negative change from baseline indicates shortening and a positive change from baseline indicates prolongation of QRS interval.
Outcome Time Frame
Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose
Outcome Measure
Change From Time-Matched Baseline in QRS Interval
Outcome Description
PR interval is defined as the time between the start of the P wave and the beginning of the QRS complex on ECG. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measures mixed effects linear model. A negative change from baseline indicates shortening and a positive change from baseline indicates prolongation of PR interval.
Outcome Time Frame
Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose
Outcome Measure
Change From Time-Matched Baseline in PR Interval
Outcome Description
Heart rate was assessed using the ECG. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measure mixed effects linear model. A negative change from baseline indicates decrease in heart rate.
Outcome Time Frame
Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose
Outcome Measure
Change From Time-Matched Baseline in Heart Rate
Outcome Time Frame
Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose
Outcome Measure
Cmax: Maximum Observed Plasma Concentration for Sapanisertib
Outcome Time Frame
Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose
Outcome Measure
Tmax: Time to Reach Cmax for Sapanisertib
Outcome Time Frame
Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose
Outcome Measure
AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Measurable Concentration for Sapanisertib
Outcome Time Frame
Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose
Outcome Measure
AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for Sapanisertib
Outcome Time Frame
Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose
Outcome Measure
T1/2: Terminal Elimination Half-life for Sapanisertib
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Nicole Nevadunsky
Investigator Email
nnevadun@montefiore.org
Investigator Phone
718-405-8082