Sirolimus or Everolimus or Temsirolimus and Vorinostat in Advanced Cancer

NCT01087554 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2009-0729NCI-2011-00562
• Study Type: interventional
• Target: 249
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Cancer

Keywords

Advanced Cancer; Sirolimus; Rapamune; mTOR Inhibitor; Histone Deacetylase Inhibitor; Vorinostat; SAHA; Suberoylanilide Hydroxamic Acid; MSK-390; Zolinza; Everolimus; Afinitor; Zortress; RAD001; Temsirolimus; CCI-779; Torisel

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  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 treated with less than 2 DLTs.

  28 days

Secondary Outcomes (1)

• Tumor Response

  After 4, 28 day cycles

Study Arms (3)

Arm A: Vorinostat + Sirolimus

EXPERIMENTAL

Escalation Phase: Vorinostat starting dose 100 mg by mouth on Days 7 - 28 of Cycle 1; For all other cycles, dose of 100 mg Days 1-28. Expansion Phase starting dose: MTD from Escalation Phase. Escalation Phase: Sirolimus starting dose1 mg by mouth on Days 1 - 28. Expansion Phase starting dose: MTD from Escalation Phase.

Drug: Sirolimus; Drug: Vorinostat

Arm B: Vorinostat + Everolimus

EXPERIMENTAL

Escalation and Expansion Phase: Vorinostat dose 300 mg by mouth on Days 7 - 28. Rest of cycles: 300 mg by mouth on Days 1 - 28. Escalation Phase: Everolimus starting dose 5 mg by mouth on Days 1 - 28. Expansion Phase: MTD from Escalation Phase.

Drug: Vorinostat; Drug: Everolimus

Arm C: Vorinostat + Temsirolimus

EXPERIMENTAL

Escalation and Expansion Phase: Vorinostat dose 300 mg by mouth on Days 7 - 28. Rest of cycles: 300 mg by mouth on Days 1 - 28. Escalation Phase: Temsirolimus starting dose 12.5 mg by vein on Days 1, 8, 15, 22. Expansion Phase: MTD from Escalation Phase.

Drug: Vorinostat; Drug: Temsirolimus

Interventions

Sirolimus DRUG

Escalation Phase: Sirolimus starting dose1 mg by mouth on Days 1 - 28. Expansion Phase starting dose: MTD from Escalation Phase.

Also known as: Rapamune

Arm A: Vorinostat + Sirolimus

Vorinostat DRUG

Arm A - Escalation Phase: Vorinostat starting dose 100 mg by mouth on Days 7 - 28 of Cycle 1; For all other cycles, dose of 100 mg Days 1-28. Expansion Phase starting dose: MTD from Escalation Phase. Arm B + Arm C - Escalation and Expansion Phase: Vorinostat dose 300 mg by mouth on Days 7 - 28. Rest of cycles: 300 mg by mouth on Days 1 - 28.

Also known as: SAHA, Suberoylanilide Hydroxamic Acid, MSK-390, Zolinza

Arm A: Vorinostat + Sirolimus; Arm B: Vorinostat + Everolimus; Arm C: Vorinostat + Temsirolimus

Everolimus DRUG

Escalation Phase: Everolimus starting dose 5 mg by mouth on Days 1 - 28. Expansion Phase: MTD from Escalation Phase.

Also known as: Afinitor, Zortress, RAD001

Arm B: Vorinostat + Everolimus

Temsirolimus DRUG

Escalation Phase: Temsirolimus starting dose 12.5 mg by vein on Days 1, 8, 15, 22. Expansion Phase: MTD from Escalation Phase.

Also known as: CCI-779, Torisel

Arm C: Vorinostat + Temsirolimus

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a histologically-confirmed metastatic or locally advanced cancer that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy that increases survival by at least three months does not exist
• There is no limit on the number of prior treatment regimens
• Patients must be off prior cytotoxic chemotherapy for at least three weeks. For biologic or targeted therapy, there should be five half lives or three weeks, whichever is shorter, between their last treatment and the first dose on this trial.
• Patients may receive palliative radiation therapy before or during treatment on protocol, provided that there is measurable or evaluable disease out of the radiation field. Patients may receive palliative radiation therapy, if needed, 48 hours after last dose of investigational drug. In addition patients may be enrolled on trial seven days following palliative radiation. We will closely monitor for the appearance of radiation recall reactions. Hormonal therapy may continue in patients who have been on such treatment for three months or longer.
• ECOG performance status 0-3
• Patients must have adequate organ and marrow function as defined by: absolute neutrophil count \>/= 1000uL, platelets \>/= 50,000uL, bilirubin \</=2mg/dL (exceptions may apply to benign non-malignant indirect hyperbilirubinemia such as Gilbert syndrome), ALT \</= 2 x ULN or \</=5x ULN if liver metastases present, creatinine \</= 2mg/dL
• As the effect of sirolimus or everolimus or temsirolimus and vorinostat in combination on the developing human fetus is not known, women of child-bearing potential and men must agree to use adequate contraception (abstinence; hormonal or barrier method of birth control) for the study and at least 3 months after completion
• Female patients with child-bearing potential must have a negative serum or urine pregnancy test within 7 days of study enrollment. Nursing mothers should discontinue nursing
• Ability to understand and the willingness to sign a written informed consent document
• Measurable or evaluable disease
• Patient must be able to swallow pills

You may not qualify if:

• Myocardial infarction within 3 months prior to starting treatment
• Concomitant use of phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital or St. Johns wort, cyclosporine, diltiazem, ketoconazole should be discontinued if possible. The list of CYP3A4 inhibitors: http://medicine.iupui.edu/clinpharm/ddis/clinical-table/
• Patient has a known hypersensitivity to the components of study drugs, its analogues, or drugs of similar chemical or biologic composition
• Patient is pregnant or breastfeeding
• Major surgical procedure within 28 days of day 1 of therapy

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Janku F, Park H, Call SG, Madwani K, Oki Y, Subbiah V, Hong DS, Naing A, Velez-Bravo VM, Barnes TG, Hagemeister FB, Falchook GS, Karp DD, Wheler JJ, Piha-Paul SA, Garrido-Laguna I, Shpall EJ, Fayad LE, Neelapu SS, Meric-Bernstam F, Kurzrock R, Fanale MA. Safety and Efficacy of Vorinostat Plus Sirolimus or Everolimus in Patients with Relapsed Refractory Hodgkin Lymphoma. Clin Cancer Res. 2020 Nov 1;26(21):5579-5587. doi: 10.1158/1078-0432.CCR-20-1215. Epub 2020 Oct 14.

  PMID: 33055173 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Interventions

Sirolimus; Vorinostat; Everolimus; temsirolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• David S Hong, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2010
• First Posted: March 16, 2010
• Study Start: March 1, 2010
• Primary Completion (Estimated): August 18, 2026
• Study Completion (Estimated): August 18, 2026
• Last Updated: January 16, 2026

Record last verified: 2026-01

Locations

US (1)