Effect of Sapanisertib (MLN0128) on the QTc Interval in Participants With Advanced Solid Tumors

NCT02197572 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: C31002U1111-1156-4099
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 5

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.

Conditions

Advanced Solid Tumors

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval

  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.

  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 (13)

• Number of Participants With Atleast One Adverse Event (AE) and Serious Adverse Event (SAE)

  From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months)

• Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Reported as AE

  From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months)

• Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Reported as AE

  From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months)

• Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB)

  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

• Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF)

  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

Study Arms (1)

Sapanisertib

EXPERIMENTAL

Sapanisertib starting dose of 40 mg, capsules, orally, once, on Day 1, Cycle 1 (28 days cycle) followed by sapanisertib 30 mg, capsules, orally, once weekly (QW) starting on Cycle 1, Day 8 based on safety and tolerability and as per investigator's discretion up to disease progression, unacceptable sapanisertib-related toxicity, withdrawal of consent, or for up to 12 months (whichever occurred first).

Drug: Sapanisertib

Interventions

Sapanisertib DRUG

Sapanisertib capsules.

Also known as: MLN0128, INK128, TAK-228

Sapanisertib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Calithera Biosciences, Inc: lead

Study Sites (5)

Unknown Facility

Sarasota, Florida, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

The Bronx, New York, United States

Location

Unknown Facility

Oklahoma City, Oklahoma, United States

Location

Unknown Facility

Dallas, Texas, United States

Location

Related Publications (1)

• 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.

  PMID: 32488989 DERIVED

MeSH Terms

Interventions

sapanisertib

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2014
• First Posted: July 22, 2014
• Study Start: September 15, 2014
• Primary Completion: June 10, 2016
• Study Completion: February 28, 2019
• Last Updated: January 23, 2023
• Results First Posted: March 3, 2020

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

US (5)