NCT03154294

Evaluation of the Safety and Tolerability of TAK-228 With TAK-117 and Paclitaxel in Advanced Solid Tumors

A Phase 1 Evaluation of the Safety and Tolerability of TAK-228 in Combination With TAK-117 and Paclitaxel in Advanced Solid Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: Avera McKennan Hospital & University Health Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label, cohort study to determine the feasibility and tolerability of the combination of TAK-228 and TAK-117 given on days 2-4, 9-11, 16-18, and 23-25 with paclitaxel on days 1, 8, and 15 for one 28-day cycle in patients with advanced solid tumors.

Detailed description

The goal of this study is to determine a tolerated dose of the combination of TAK-228, TAK-117 and paclitaxel. To do this, investigators will estimate the maximum tolerated dose that is defined as the dose level at which less than one-third of patients will experience a dose-limiting toxicity. A traditional dose escalation design will be used, beginning with the lowest dose level and escalating to the maximum allowable dose level as specified in the protocol. Three patients will be treated one at a time at a given dose level. A maximum of 5 dosing levels results in a maximum sample size of n=30 subjects. Adverse events will be defined using the Common Toxicity Criteria v. 4.0. dose-limiting toxicity is defined as: * Grade 3 or higher nonhematologic toxicity, despite adequate treatment, except for the following: * Grade 3 hyperglycemia lasting ≤14 days (all patients should receive optimal antiglycemic treatment, including insulin, as clinically indicated). * Grade 3 rash lasting ≤3 days (all patients should receive topical steroid treatment, oral antihistamines, and oral steroids, if necessary). * Inadequately treated Grade 3 nausea and/or vomiting and Grade 3 diarrhea (all patients should receive optimal antiemetic and/or antidiarrheal prophylaxis and/or treatment). * Grade 4 neutropenia lasting \>7 days in the absence of growth factor support. * Grade 4 neutropenia of any duration accompanied by fever ≥38.5°C and/or systemic infection. * Any other ≥Grade 4 hematologic toxicity. * Inability to administer at least 75% of planned doses of TAK-228 within Cycle 1, due to study drug-related toxicity. * Any clinically significant occurrence that the investigator and sponsor agree would place patients at an undue safety risk. Patients experiencing any grade 3 or more hematologic toxicity attributed to the treatment will hold all therapy until resolution of the toxicity to grade 2 or less. If toxicity persists, the patients will be removed from the study. Upon resolution of the toxicity, the patient will restart treatment at the original dose at the discretion of the investigators. One of the following outcomes will determine the treatment of subsequent patients: * If none of the three patients experiences a dose-limiting toxicity, the next group of patients will be entered in the next higher dose cohort. All patients within a cohort must have completed at least once cycle (28 days) prior to initiation of the next cohort of patients. * If one of the three patients experiences a dose-limiting toxicity, three more patients will be accrued at the current dose level. Subsequently, if only one of the six patients treated at this level experiences a dose-limiting toxicity, the dose will be escalated to the next higher dose in the next group of patients. If two or more of the six patients experiences a dose-limiting toxicity, the maximum tolerated dose has been exceeded and is defined as the previous dose at which no more than 1/3 experienced a dose-limiting toxicity. * If at least two of the three experience a dose-limiting toxicity, the maximum tolerated dose has been exceeded and is defined as the previous dose at which no more than 1/3 experienced a dose-limiting toxicity. If the lowest allowable dose level exceeds the maximum tolerated dose, the study will be terminated and the combination will not be deemed safe for use in this population. Additionally, the highest dose level will not be exceeded, even if no dose-limiting toxicities are experienced at that dose. The adverse events overall and by individual adverse events categories will be summarized. Serious adverse events will be summarized in a similar manner. These summaries will be performed overall and for each dose cohort. Investigators will summarize all events as well as the highest grade for a given subject. Investigators will summarize the number of subjects that exhibit a dose-limiting toxicity at each dose cohort and describe the dose-limiting toxicity for each subject, if applicable.

Conditions

• Advanced Solid Tumor

Interventions

Type	Name	Description
DRUG	paclitaxel	Paclitaxel will be diluted prior to infusion in 0.9% Sodium Chloride for Injection, USP; 5% Dextrose Injection, USP; 5% Dextrose and 0.9% Sodium Chloride Injection, USP; or 5% Dextrose in Ringer's Injection to a final concentration of 0.3 to 1.2mg/mL. At ambient temperature (approximately 25°C) and room lighting conditions the solution is physically and chemically stable for up to 27 hours. The diluted product will be prepared and stored in glass, polypropylene, or polyolefin containers; DEHP-containing (polyvinyl chloride (PCV)) containers should not be used. Paclitaxel will be administered using a vented Paclitaxel set with in-line 0.22-micron filter and run over 1 hour.
DRUG	TAK-228	TAK-228 will be provided in 30-ct, 60-cc high density polyethylene (HDPE) bottles with polypropylene, child-resistant caps and induction seal. TAK-228 will be administered on an empty stomach. It is recommended that each dose of TAK-228 + TAK-117 be given PO with 8 ounces (240 mL) of water. Patients should be instructed to refrain from eating and drinking (except for water and prescribed medications) for 2 hours before and 1 hour after each dose.
DRUG	TAK-117	TAK-117 will be provided in 30-ct, 60-cc high density polyethylene (HDPE) bottles with polypropylene, child-resistant caps and induction seal. TAK-117 will be administered on an empty stomach. It is recommended that each dose of TAK-228 + TAK-117 be given PO with 8 ounces (240 mL) of water. Patients should be instructed to refrain from eating and drinking (except for water and prescribed medications) for 2 hours before and 1 hour after each dose.

Timeline

• Start date: 2017-07-06
• Primary completion: 2020-11-20
• Completion: 2022-11-20
• First posted: 2017-05-16
• Last updated: 2024-07-26
• Results posted: 2024-07-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study