Sapanisertib and Metformin in Treating Patients With Advanced or Metastatic Relapsed or Refractory Cancers
- Conditions
- Advanced Malignant Solid NeoplasmMetastatic Malignant Solid NeoplasmRecurrent Malignant Solid NeoplasmRefractory Neoplasm
- Interventions
- 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
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (metformin, sapanisertib) Laboratory Biomarker Analysis Patients 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 Study Patients 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) Metformin Patients 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) Sapanisertib Patients 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
Name Time Method Incidence of serious adverse events Up 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 values Up 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 measurements Up 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 symptoms Up 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 neurotoxicity Up to 4 years Descriptive statistics will be provided on the grade and type of toxicity by dose level.
- Secondary Outcome Measures
Name Time Method 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 events Up 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 toxicities Up to 4 years Descriptive statistics will be provided on the grade and type of toxicity by dose level.
Withdrawals from study due to adverse events Up 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 events Up 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 study Up 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 dosage Up 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 level Up 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 level Up 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 level Up 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