Clinical trial · Interventional
Sirolimus or Everolimus or Temsirolimus and Vorinostat in Advanced Cancer
A Phase I Trial of Sirolimus or Everolimus or Temsirolimus (mTOR Inhibitor) and Vorinostat (Histone Deacetylase Inhibitor) in Patients With Advanced Cancer
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Advanced Cancer | Malignant Neoplasm | CURATED_BROADER | 0.78 |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Everolimus | Drug | Everolimus | ALIAS |
| Sirolimus | Drug | Sirolimus | ALIAS |
| Temsirolimus | Drug | Temsirolimus | ALIAS |
| Vorinostat | Drug | Vorinostat | ALIAS |
Design
Arms and outcomes
Arms (3)
- type
- EXPERIMENTAL
- label
- Arm A: Vorinostat + Sirolimus
- description
- 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.
- interventionNames
- Drug: Sirolimus
- Drug: Vorinostat
- type
- EXPERIMENTAL
- label
- Arm B: Vorinostat + Everolimus
- description
- 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.
- interventionNames
- Drug: Vorinostat
- Drug: Everolimus
Eligibility
Eligibility (as posted)
- Sex
- All
Show eligibility criteria text
Inclusion Criteria: 1. 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 2. There is no limit on the number of prior treatment regimens 3. 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. 4. 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. 5. ECOG performance status 0-3 6. 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 7. 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 8. 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 9. Ability to understand and the willingness to sign a written informed consent document 10. Measurable or evaluable disease 11. Patient must be able to swallow pills Exclusion Criteria: 1. Myocardial infarction within 3 months prior to starting treatment 2. 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/ 3. Patient has a known hypersensitivity to the components of study drugs, its analogues, or drugs of similar chemical or biologic composition 4. Patient is pregnant or breastfeeding 5. Major surgical procedure within 28 days of day 1 of therapy 6. Use of any other concurrent investigational agents or anticancer agents except for hormonal therapy as outlined in inclusion criteria
References
Publications (1)
- DERIVEDJanku 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