Clinical trial NCT02197572: Effect of Sapanisertib (MLN0128) on the QTc Interval in Participants With Advanced Solid Tumors
Official title: A Phase 1 Study to Evaluate the Effect of MLN0128 on the QTc Interval in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Drug therapy
Lead sponsor: Calithera Biosciences, Inc
Sponsor class: INDUSTRY
First posted: 2014-07-22
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

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.

Primary outcomes:
measure: Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval
timeFrame: 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 outcomes:
measure: Number of Participants With Atleast One Adverse Event (AE) and Serious Adverse Event (SAE)
timeFrame: From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months)
measure: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Reported as AE
timeFrame: From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months)
measure: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Reported as AE
timeFrame: From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months)
measure: Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB)
timeFrame: 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
measure: Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF)
timeFrame: 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
measure: Change From Time-Matched Baseline in QRS Interval
timeFrame: 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
measure: Change From Time-Matched Baseline in PR Interval
timeFrame: 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
measure: Change From Time-Matched Baseline in Heart Rate
timeFrame: 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
measure: Cmax: Maximum Observed Plasma Concentration for Sapanisertib
timeFrame: Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose
measure: Tmax: Time to Reach Cmax for Sapanisertib
timeFrame: Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose
measure: AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Measurable Concentration for Sapanisertib
timeFrame: Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose
measure: AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for Sapanisertib
timeFrame: Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose
measure: T1/2: Terminal Elimination Half-life for Sapanisertib
timeFrame: Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose
Other outcomes:
Locations:
city: Sarasota
country: United States
state: Florida
city: Saint Louis
country: United States
state: Missouri
city: Bronx
country: United States
state: New York
city: Oklahoma City
country: United States
state: Oklahoma
city: Dallas
country: United States
state: Texas
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Patel C, Goel S, Patel MR, Rangachari L, Wilbur JD, Shou Y, Venkatakrishnan K, Lockhart AC. Phase 1 Study to Evaluate the Effect of the Investigational Anticancer Agent Sapanisertib on the QTc Interval in Patients With Advanced Solid Tumors. Clin Pharmacol Drug Dev. 2020 Oct;9(7):876-888. doi: 10.1002/cpdd.808. Epub 2020 Jun 2.