Trial record 1 of 1 for:    NCT01087554
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Sirolimus and Vorinostat in Advanced Cancer

This study is currently recruiting participants.
Verified February 2014 by M.D. Anderson Cancer Center
Information provided by (Responsible Party):
M.D. Anderson Cancer Center Identifier:
First received: March 15, 2010
Last updated: February 19, 2014
Last verified: February 2014

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.

Condition Intervention Phase
Advanced Cancer
Drug: Sirolimus
Drug: Vorinostat
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Sirolimus (mTOR Inhibitor) and Vorinostat (Histone Deacetylase Inhibitor) in Patients With Advanced Cancer

Resource links provided by NLM:

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Sirolimus and Vorinostat [ Time Frame: Every 28 day cycle ] [ Designated as safety issue: Yes ]
    MTD defined as highest dose level in which 6 patients have been treated with less than 2 DLTs in the first cycle (4 weeks) of treatment. 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.

Estimated Enrollment: 219
Study Start Date: March 2010
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sirolimus + Vorinostat
Sirolimus starting oral dose level 1 mg daily on Days 1-28. Vorinostat starting dose level 100 mg orally on Days 7-28 of Cycle 1; For all other cycles, dose of 100 mg Days 1-28.
Drug: Sirolimus
Starting oral dose level 1 mg daily on Days 1-28
Other Name: Rapamune
Drug: Vorinostat
Starting dose level 100 mg orally on Days 7-28 of Cycle 1; For all other cycles, dose of 100 mg Days 1-28.
Other Names:
  • SAHA
  • Suberoylanilide Hydroxamic Acid
  • MSK-390
  • Zolinza

  Show Detailed Description


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 in the absence of Gilbert's 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:
  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
  Contacts and Locations
Please refer to this study by its identifier: NCT01087554

Contact: Filip Janku, MD, PHD 713-563-1930

United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Principal Investigator: Filip Janku, MD, PHD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01087554     History of Changes
Other Study ID Numbers: 2009-0729
Study First Received: March 15, 2010
Last Updated: February 19, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
mTOR Inhibitor
Histone Deacetylase Inhibitor
Suberoylanilide Hydroxamic Acid

Additional relevant MeSH terms:
Histone Deacetylase Inhibitors
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on April 23, 2014