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Sapanisertib and Metformin in Treating Patients With Advanced or Metastatic Relapsed or Refractory Cancers | Clinical Trials | Clareo Health

COMPLETEDPHASE1

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

Phase I Study of TAK-228 (MLN0128) in Combination With Metformin in Patients With Advanced Cancers

NCT03017833•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Inclusion:
•1. Male or female patients 18 years or older.
•2. 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of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
•3. Female patients 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 1 highly effective method of contraception and one additional effective (barrier) method at the same time, from the time of signing the informed consent through 90 days (or longer as mandated by local labeling \[eg USPI, SmPC, etc\] 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 patient (Periodic abstinence \[e.g, calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.) MUST have a negative serum or urine pregnancy test within 7 days of initiating protocol treatment unless prior hysterectomy or menopause (defined as 12 consecutive months without menstrual activity).
•4. CONTINUED FROM #3: Patients should not become pregnant or breastfeed while on this study. The effects of TAK-228 and metformin on the developing human fetus are unknown. Should a woman become pregnant or suspect she is pregnant, she should inform her treatment physician immediately. Male patients, even if surgically sterilized (ie, status post-vasectomy), who: Agree to practice highly effective barrier contraception during the entire study treatment period and through 120 days 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 patient, as described in #3 above. Agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of study drug.
•5. Patients must have a diagnosis of advanced or metastatic malignancy that is refractory to standard therapies, who have relapsed after standard therapy, or whose cancers have no standard therapy that induces a CR rate of at least 10% or improves survival by at least three months.
•6. Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status \</= 1.
•7. Adequate organ function, as specified below, within 7 days before the first dose of study drug: a) Bone marrow reserve consistent with: absolute neutrophil count (ANC) \>/= 1.5 x 10\^9/L; platelet count \>/= 100 x 10\^9/L; hemoglobin \>/= 9 g/dL without transfusion within 1 week preceding study drug administration; b) Hepatic: total bilirubin \</= 1.5 x upper limit of normal (ULN), transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase-AST/SGOT and alanine aminotransferase/serum glutamic pyruvic transaminase-ALT/SGPT) \</= 2.5 x ULN (\</= 5 x ULN if liver metastases are present); c) Renal: creatinine clearance \>/=50 mL/min based either on Cockroft-Gault estimate or based on urine collection (12 or 24 hour); d) Metabolic: fasting serum glucose (\</= 130 mg/dL) and fasting triglycerides \</= 300 mg/dL.
•8. Ability to swallow oral medications.
•9. Patients with diabetes are allowed and may be on antidiabetic treatment other than Metformin. The diabetes must be under control within normal range (HbA1C \</=7%).
+8 more criteria

Exclusion Criteria

•6. History of any of the following within the last 6 months prior to study entry: Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures; Ischemic cerebrovascular event, including TIA and artery revascularization procedures; Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia); Placement of a pacemaker for control of rhythm; New York Heart Association (NYHA) Class III or IV heart failure; Pulmonary embolism.
•7. Significant active cardiovascular or pulmonary disease at the time of study entry, including: Uncontrolled high blood pressure (i.e., systolic blood pressure \>150mm Hg, diastolic blood pressure \> 90 mm Hg). Use of anti-hypertensive agents to control hypertension before Cycle1 Day 1 is allowed.; Pulmonary hypertension; Uncontrolled asthma or O2 saturation \< 90% by ABG (Arterial Blood Gas) analysis or pulse oximetry on room air; Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement; Medically significant (symptomatic) bradycardia; History of arrhythmia requiring an implantable cardiac defibrillator; Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval \> 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes).
•8. Previous treatment with dual PI3K/mTOR inhibitors, TORC1/2 inhibitors or TORC1 inhibitors
•9. Patients receiving corticosteroids (either IV or oral steroids, excluding inhalers or low-dose hormone replacement therapy) within 1 week before administration of the first dose of study drug.
•10. Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise participation of the patient in the study.
•11. Patients with major surgery within 30 days prior to entering the study.
•12. History of hypersensitivity to TAK-228 or metformin.
•13. Patients who have a history of brain metastasis are eligible for the study provided that all the following criteria are met: A. Brain metastases which have been treated B. No evidence of disease progression for \>/= 3 months before the first dose of study drug. C. No hemorrhage after treatment D. Off-treatment with dexamethasone for 4 weeks before administration of the first dose of TAK-228 E. No ongoing requirement for dexamethasone or anti-epileptic drugs
•14. Known human immunodeficiency virus infection.
•15. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection.
+2 more criteria

Locations (1)

M D Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

March 12, 2018

Primary Completion Date

December 21, 2022

Completion Date

December 21, 2022

Last Updated

October 4, 2023

Enrollment

ACTUAL participants

Conditions

Advanced Malignant Solid NeoplasmMetastatic Malignant Solid NeoplasmRecurrent Malignant Solid NeoplasmRefractory Neoplasm

Interventions

Laboratory Biomarker Analysis

OTHER

Metformin

DRUG

Pharmacological Study

OTHER

Sapanisertib

DRUG

Testing the Safety and Efficacy of the Combination of Two Anti-cancer Drugs, ZEN003694 and Abemaciclib, for Adult and Pediatric Patients (12-17 Years) With Metastatic or Unresectable NUT Carcinoma, Breast Cancer and Other Solid Tumors

NCT05372640

Anatomic Stage III Breast Cancer AJCC v8Anatomic Stage IV Breast Cancer AJCC v8+6 more

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RECRUITINGPHASE2

Testing the Use of Neratinib or the Combination of Neratinib and Palbociclib Targeted Treatment for HER2+ Solid Tumors (A ComboMATCH Treatment Trial)

NCT06126276

Malignant Female Reproductive System NeoplasmMalignant Solid Neoplasm+2 more

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: October 4, 2023Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

Testing the Safety and Efficacy of the Combination of Two Anti-cancer Drugs, ZEN003694 and Abemaciclib, for Adult and Pediatric Patients (12-17 Years) With Metastatic or Unresectable NUT Carcinoma, Breast Cancer and Other Solid Tumors

Testing the Use of Neratinib or the Combination of Neratinib and Palbociclib Targeted Treatment for HER2+ Solid Tumors (A ComboMATCH Treatment Trial)

Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial

IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors

Testing A New Anti-cancer Drug Combination, Entinostat and ZEN003694, for Advanced and Refractory Solid Tumors

Personalized Antibody-Drug Conjugate Therapy Based on RNA and Protein Testing for the Treatment of Advanced or Metastatic Solid Tumors (The ADC MATCH Screening and Treatment Trial)