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A Pharmacodynamic Study of Sirolimus and Metformin in Patients With Advanced Solid Tumors

NCT02145559 · Status: COMPLETED · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 24

Last updated 2019-04-22

No results posted yet for this study

Summary

Given the role of mTOR signaling and probable synergistic activity of combining sirolimus and metformin in patients with advanced solid tumors, the investigators hypothesize that:

1. The combination of metformin plus sirolimus will result in reduction of p4EBP1, p70S6K and pAKT more than sirolimus alone in peripheral blood T cells (PBTC).
2. The combination of metformin plus sirolimus will result in decreased levels of serum biomarkers including fasting insulin, C-peptide, glucose, triglycerides, LDH, IGF-1, IGF-1R, IGF-BP and leptin, but an increase in adiponectin in peripheral blood.
3. Expression of active forms of AMPK, mTOR, PI3K, PTEN loss, AKT, LKB1, P62, LC3, and/or ULK1 in the tumor tissue (original pathology) will be predictive of response to combination therapy. This will be an exploratory hypothesis for this study.
4. Sirolimus induced toxicity, especially hyperglycemia and hypertriglyceridemia, will be mitigated by combining sirolimus with metformin.
5. Metformin plus sirolimus will have promising anti-cancer activity and this activity will correlate with decreases in the above biomarkers. This will be an exploratory hypothesis for this study.

Conditions

  • Breast Neoplasms
  • Lung Neoplasms
  • Cancer of Liver
  • Lymphoma
  • Cancer of Kidney

Interventions

DRUG

Metformin XR

DRUG

Delayed Metformin

DRUG

Sirolimus

Sponsors & Collaborators

  • University of Chicago

    lead OTHER

Principal Investigators

  • Manish Sharma, M.D. · University of Chicago

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2014-04-30
Primary Completion
2016-11-15
Completion
2018-07-31

Countries

  • United States

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02145559 on ClinicalTrials.gov