NCT01087554

A Phase I Trial of Sirolimus or Everolimus or Temsirolimus (mTOR Inhibitor) and Vorinostat (Histone Deacetylase Inhibitor) in Patients With Advanced Cancer

Active, enrolled Phase 1 Last updated 14 January 2026

What this trial tests

Phase 1 trial testing Sirolimus in Advanced Cancer in 249 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

1 March 2010

Primary endpoint
18 August 2026

18 August 2026

Quick facts

Lead sponsor	M.D. Anderson Cancer Center
Phase	Phase 1
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	249
Start date	1 March 2010
Primary completion	18 August 2026
Estimated completion	18 August 2026
Sites	1 location across United States

Drugs / interventions tested

• Sirolimus (sirolimus) — full drug profile →
• Vorinostat
• Everolimus (everolimus) — full drug profile →
• Temsirolimus (temsirolimus) — full drug profile →

Conditions studied

• Advanced Cancer — all drugs for Advanced Cancer →

Sponsor

M.D. Anderson Cancer Center — full company profile →

Who can join

Eligibility, any sex, with Advanced Cancer. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Maximum Tolerated Dose (MTD)
  Time frame: 28 days
  Maximum tolerated dose (MTD) defined by dose-limiting toxicities (DLTs) that 1) occur during the first four weeks of therapy, 2) are related to the study medications (attributions: possible, probable, and likely) and 3) fulfill one of the following criteria (as graded by the NCI Common Terminology Criteria for Adverse Events). MTD is defined as highest dose level in which 6 patients have been trea

Sponsor's own description

The goal of this clinical research study is to find the highest tolerable dose of the combination vorinostat given in combination with either sirolimus, everolimus or temsirolimus that can be given to patients with advanced cancer. The safety of this drug combination will also be studied.

The Study Drugs:

Vorinostat is designed to prevent or slow down the growth of cancer cells by blocking proteins.

Everolimus is designed to stop cells from dividing. This may stop or slow the growth or spread of cancer cells.

Temsirolimus is designed to block a protein called mTOR (a protein that is thought to cause cancer cells to grow) inside the cancer cell. This may interfere with the growth or spread of cancer cells or possibly kill them.

Sirolimus is designed to block a protein called mTOR inside the cancer cell. This may interfere with the growth or spread of cancer cells or possibly kill the cancer cells.

This is an investigational study. Sirolimus is FDA approved and commercially available as an anti-rejection drug for kidney transplant recipients. Everolimus is FDA-approved and commercially available for the treatment of pancreatic neuroendocrine tumor, subependymal giant cell astrocytoma, and renal cell carcinoma. Temsirolimus is FDA approved and commercially available for the treatment of renal cell carcinoma. Vorinostat is FDA approved and commercially available for the treatment of cutaneous T-cell lymphoma. The combination of these drugs is investigational.

Up to 249 patients will take part in this study. All will be enrolled at MD Anderson.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Histone deacetylase 6 in cancer.
   Li T, Zhang C, Hassan S, Liu X, et al · · 2018 · cited 261× · PMID 30176876 · DOI 10.1186/s13045-018-0654-9
2. Inhibition of BET Proteins and Histone Deacetylase (HDACs): Crossing Roads in Cancer Therapy.
   Manzotti G, Ciarrocchi A, Sancisi V. · · 2019 · cited 60× · PMID 30841549 · DOI 10.3390/cancers11030304
3. KRASness and PIK3CAness in patients with advanced colorectal cancer: outcome after treatment with early-phase trials with targeted pathway inhibitors.
   Garrido-Laguna I, Hong DS, Janku F, Nguyen LM, et al · · 2012 · cited 42× · PMID 22675430 · DOI 10.1371/journal.pone.0038033
4. Phase I dose-escalation study of the mTOR inhibitor sirolimus and the HDAC inhibitor vorinostat in patients with advanced malignancy.
   Park H, Garrido-Laguna I, Naing A, Fu S, et al · · 2016 · cited 41× · PMID 27589687 · DOI 10.18632/oncotarget.11750
5. PI3K/AKT/mTOR Axis in Cancer: From Pathogenesis to Treatment.
   Jiang M, Zhang K, Zhang Z, Zeng X, et al · · 2025 · cited 40× · PMID 40740483 · DOI 10.1002/mco2.70295
6. New targeted therapies in pancreatic cancer.
   Seicean A, Petrusel L, Seicean R. · · 2015 · cited 38× · PMID 26034349 · DOI 10.3748/wjg.v21.i20.6127
7. The Epigenetic Profile of Tumor Endothelial Cells. Effects of Combined Therapy with Antiangiogenic and Epigenetic Drugs on Cancer Progression.
   Ciesielski O, Biesiekierska M, Panthu B, Vialichka V, et al · · 2020 · cited 36× · PMID 32283668 · DOI 10.3390/ijms21072606
8. The role of metabolic ecosystem in cancer progression - metabolic plasticity and mTOR hyperactivity in tumor tissues.
   Sebestyén A, Dankó T, Sztankovics D, Moldvai D, et al · · 2021 · cited 35× · PMID 35029792 · DOI 10.1007/s10555-021-10006-2