A Phase I Study Of The Pharmacokinetics And Safety Of Ipatasertib In Chinese Patients With Locally Advanced Or Metastatic Solid Tumors.
Overview
- Phase
- Phase 1
- Intervention
- Ipatasertib
- Conditions
- Solid Tumors
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- AUC (0-inf) after a single dose and AUC (0-24) after single and multiple doses of Ipatasertib
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
A Phase I, Open-Label study designed to assess the pharmacokinetics (PK), safety and tolerability of ipatasertib in Chinese participants. Approximately 20 Chinese participants (12 PK-evaluable participants) with locally advanced or metastatic solid tumors for whom standard therapy either does not exist or has proven ineffective will be enrolled to provide sufficient data. Participants will receive a 400-mg ipatasertib dose (two 200-mg tablets) daily orally (PO). Participants deriving clinical benefit may be offered continued treatment with ipatasertib until disease progression, at the discretion of the investigator (as assessed by the investigator) or until the study is terminated by the Sponsor.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically documented locally advanced or metastatic solid tumor that has progressed or failed to respond to at least one prior regimen.
- •Not a candidate for regimens known to provide clinical benefit.
- •Evaluable or measurable disease according to RECIST, v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
- •Life expectancy of \>= 12 weeks.
- •Adequate haematologic and organ function within 14 days prior to initiation of study treatment.
- •Women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating eggs.
- •Men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.
- •Participants must reside in the People's Republic of China
Exclusion Criteria
- •Leptomeningeal disease as the only manifestation of the current tumor.
- •Type 1 or 2 diabetes mellitus requiring insulin at study entry.
- •Inability or unwillingness to swallow pills.
- •Malabsorption syndrome or other condition that would interfere with enteral absorption.
- •Known and untreated, or active CNS metastases (progressing or requiring anticonvulsants for symptomatic control).
- •Congenital long QT syndrome or corrected QT interval (QTc) \> 480 ms.
- •Active congestive heart failure or ventricular arrhythmia requiring medication.
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring weekly paracentesis for 3 consecutive weeks prior to initiation of ipatasertib treatment.
- •Severe infections within 4 weeks prior to screening including but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
- •Requirement for any daily supplemental oxygen.
Arms & Interventions
Ipatasertib as a Single Agent
Participants will receive a 400-mg Ipatasertib dose (two 200-mg tablets) orally (PO) daily (QD). This study has three study periods: a screening period (up to 14 days in length), followed by a treatment period of up to approximately 2 years (Cycle 1 will be 35 days in length, all subsequent cycles will be 28 days in length) and a 28-day follow-up period after the treatment discontinuation or study completion.
Intervention: Ipatasertib
Outcomes
Primary Outcomes
AUC (0-inf) after a single dose and AUC (0-24) after single and multiple doses of Ipatasertib
Time Frame: Up to 25 months
Maximum plasma concentration (Cmax) of Ipatasertib
Time Frame: Up to 25 months
Minimum plasma concentration (Cmin) of Ipatasertib after multiple doses of Ipatasertib
Time Frame: Up to 25 months
Time to maximum plasma concentration (tmax) of Ipatasertib
Time Frame: Up to 25 months
Terminal half-life (t1/2) of Ipatasertib and GO37220
Time Frame: Up to 25 months
Apparent clearance (CL/F) of Ipatasertib and GO37220 after single and multiple doses of Ipatasertib
Time Frame: Up to 25 months
Accumulation ratio at steady state (Rcmax) of Ipatasertib
Time Frame: Up to 25 months
Accumulation ratio will be calculated as follows: Rcmax = AUC24h,ss/AUC0-24 of Day 1.
Secondary Outcomes
- Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to 25 months)
- Percentage of Participants with Adverse Events leading to Study Treatment Discontinuation, Modification or Interruption(Up to 25 months)
- Number of Deaths(Up to 25 months)