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Sapanisertib and Metformin in Treating Patients With Advanced or Metastatic Relapsed or Refractory Cancers

Phase 1
Completed
Conditions
Advanced Malignant Solid Neoplasm
Metastatic Malignant Solid Neoplasm
Recurrent Malignant Solid Neoplasm
Refractory Neoplasm
Interventions
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Registration Number
NCT03017833
Lead Sponsor
M.D. Anderson Cancer Center
Brief Summary

This phase I trial studies the side effects and best dose of sapanisertib and metformin in treating patients with cancers that have spread to other parts of the body (advanced/metastatic), have come back (recurrent), or do not respond to treatment (refractory). Sapanisertib and metformin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability and to determine maximum tolerated dose (MTD) of the combination of sapanisertib (TAK-228) with metformin in patients with advanced cancers refractory to standard therapy.

SECONDARY OBJECTIVES:

I. To assess the clinical tumor response of this combination. II. To characterize the pharmacokinetic (PK) profile of metformin and TAK-228.

OUTLINE: This is a dose escalation study.

Patients receive metformin orally (PO) 1-3 times daily on days 1-42 and sapanisertib PO daily on days 15-42 of cycle 1. Patients then receive metformin PO daily and sapanisertib PO daily on days 1-28 of cycle 2 and beyond. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up within 30 days.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
31
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (metformin, sapanisertib)Laboratory Biomarker AnalysisPatients receive metformin PO 1-3 times daily on days 1-42 and sapanisertib PO daily on days 15-42 of cycle 1. Patients then receive metformin PO daily and sapanisertib PO daily on days 1-28 of cycle 2 and beyond. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Treatment (metformin, sapanisertib)Pharmacological StudyPatients receive metformin PO 1-3 times daily on days 1-42 and sapanisertib PO daily on days 15-42 of cycle 1. Patients then receive metformin PO daily and sapanisertib PO daily on days 1-28 of cycle 2 and beyond. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Treatment (metformin, sapanisertib)MetforminPatients receive metformin PO 1-3 times daily on days 1-42 and sapanisertib PO daily on days 15-42 of cycle 1. Patients then receive metformin PO daily and sapanisertib PO daily on days 1-28 of cycle 2 and beyond. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Treatment (metformin, sapanisertib)SapanisertibPatients receive metformin PO 1-3 times daily on days 1-42 and sapanisertib PO daily on days 15-42 of cycle 1. Patients then receive metformin PO daily and sapanisertib PO daily on days 1-28 of cycle 2 and beyond. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Primary Outcome Measures
NameTimeMethod
Incidence of serious adverse eventsUp to 4 years

Assessed by Common Terminology Criteria for Adverse Events version 4.0. Descriptive statistics will be provided on the grade and type of toxicity by dose level.

Clinical and laboratory valuesUp to 4 years

Wilcoxon's Signed-Rank Test and Fisher's exact test will be used. A mixed model accounting for patient effects will be used to analyze longitudinal data (including biomarker data) over time.

Vital sign measurementsUp to 4 years

Wilcoxon's Signed-Rank Test and Fisher's exact test will be used. A mixed model accounting for patient effects will be used to analyze longitudinal data (including biomarker data) over time.

GI symptomsUp to 4 years

Wilcoxon's Signed-Rank Test and Fisher's exact test will be used. A mixed model accounting for patient effects will be used to analyze longitudinal data (including biomarker data) over time.

Incidence of neurotoxicityUp to 4 years

Descriptive statistics will be provided on the grade and type of toxicity by dose level.

Secondary Outcome Measures
NameTimeMethod
The peak plasma concentration (Cmax)Up to 4 years

Will be determined by observation of the data.

The area under the plasma concentration-time curve (AUC)Up to 4 years

The AUC from 0 to 24 hours postdose (AUC0-24) will be calculated using the linear trapezoidal.

Elimination half-life (t1/2)Up to 4 years

Will be calculated by 0.693/k

Incidence and grade of adverse eventsUp to 4 years

Assessed by Common Terminology Criteria for Adverse Events version 4.0. Descriptive statistics will be provided on the grade and type of toxicity by dose level.

Incidence of dose limiting toxicitiesUp to 4 years

Descriptive statistics will be provided on the grade and type of toxicity by dose level.

Withdrawals from study due to adverse eventsUp to 4 years

Wilcoxon's Signed-Rank Test and Fisher's exact test will be used. A mixed model accounting for patient effects will be used to analyze longitudinal data (including biomarker data) over time.

Change in treatment regimen due to adverse eventsUp to 4 years

Wilcoxon's Signed-Rank Test and Fisher's exact test will be used. A mixed model accounting for patient effects will be used to analyze longitudinal data (including biomarker data) over time.

Death during studyUp to 4 years

Wilcoxon's Signed-Rank Test and Fisher's exact test will be used. A mixed model accounting for patient effects will be used to analyze longitudinal data (including biomarker data) over time.

Establishment of recommended phase 2 dosageUp to 42 days

Wilcoxon's Signed-Rank Test and Fisher's exact test will be used. A mixed model accounting for patient effects will be used to analyze longitudinal data (including biomarker data) over time.

Best tumor responses by dose levelUp to 4 years

Will be measured according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Wilcoxon's Signed-Rank Test and Fisher's exact test will be used. A mixed model accounting for patient effects will be used to analyze longitudinal data (including biomarker data) over time.

Overall survival by dose levelUp to 4 years

Will be measured according to RECIST version 1.1. Wilcoxon's Signed-Rank Test and Fisher's exact test will be used. A mixed model accounting for patient effects will be used to analyze longitudinal data (including biomarker data) over time.

Progression free survival by dose levelUp to 4 years

Will be measured according to RECIST version 1.1. Wilcoxon's Signed-Rank Test and Fisher's exact test will be used. A mixed model accounting for patient effects will be used to analyze longitudinal data (including biomarker data) over time.

Trial Locations

Locations (1)

M D Anderson Cancer Center

🇺🇸

Houston, Texas, United States

M D Anderson Cancer Center
🇺🇸Houston, Texas, United States

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