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History of Changes for Study: NCT01087554
Sirolimus and Vorinostat in Advanced Cancer
Latest version (submitted April 10, 2020) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 March 15, 2010 None (earliest Version on record)
2 September 15, 2010 Study Status and Study Description
3 February 18, 2011 Study Description, Study Status and Eligibility
4 June 24, 2011 Study Status
5 August 30, 2011 Contacts/Locations, Sponsor/Collaborators, Study Status, Eligibility and Study Description
6 September 23, 2011 Study Status and Eligibility
7 March 26, 2012 Study Status and Study Design
8 August 1, 2012 Study Description, Study Status, Arms and Interventions and Study Design
9 November 26, 2012 Study Status
10 May 10, 2013 Study Status, Eligibility and Study Description
11 November 11, 2013 Outcome Measures and Study Status
12 January 9, 2014 Study Description, Study Status, Eligibility and Study Design
13 February 19, 2014 Study Status, Eligibility and Study Description
14 May 13, 2014 Arms and Interventions, Outcome Measures, Study Design, Study Identification, Study Status, Eligibility and Conditions
15 November 14, 2014 Contacts/Locations, Study Status and References
16 March 26, 2015 Study Status and Eligibility
17 September 28, 2015 Study Status
18 February 11, 2016 Study Status
19 May 18, 2016 Recruitment Status, Study Status and Contacts/Locations
20 May 19, 2017 Study Status and Oversight
21 November 8, 2017 Study Description and Study Status
22 November 12, 2018 Study Status
23 May 14, 2019 Study Status
24 April 10, 2020 Recruitment Status and Study Status
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Study NCT01087554
Submitted Date:  March 15, 2010 (v1)

Open or close this module Study Identification
Unique Protocol ID: 2009-0729
Brief Title: Sirolimus and Vorinostat in Advanced Cancer
Official Title: A Phase I Trial of Sirolimus (mTOR Inhibitor) and Vorinostat (Histone Deacetylase Inhibitor) in Patients With Advanced Cancer
Secondary IDs:
Open or close this module Study Status
Record Verification: March 2010
Overall Status: Recruiting
Study Start: March 2010
Primary Completion: March 2014 [Anticipated]
Study Completion:
First Submitted: March 15, 2010
First Submitted that
Met QC Criteria:
March 15, 2010
First Posted: March 16, 2010 [Estimate]
Last Update Submitted that
Met QC Criteria:
March 15, 2010
Last Update Posted: March 16, 2010 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: M.D. Anderson Cancer Center
Responsible Party:
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: No
Open or close this module Study Description
Brief Summary:

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

PRIMARY OBJECTIVE:

To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of combination treatment with sirolimus and vorinostat in patients with advanced cancer who have progressed on standard therapy.

SECONDARY OBJECTIVES:

  • Determine preliminary assessment of antitumor efficacy of the combination of sirolimus and vorinostat in advanced cancer.
  • Define the pharmacokinetic (PK) profile of the combination of sirolimus and vorinostat.
  • Define the pharmacodynamic (PD) profile of the combination of sirolimus and vorinostat.
Detailed Description:

The Study Drugs:

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

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.

Screening Tests:

Signing this consent form does not mean that you will be able to take part in this study. You will have "screening tests" to help the doctor decide if you are eligible to take part in this study. The following tests and procedures will be performed:

  • Your medical history will be recorded, including any drugs you may be taking and your use of tobacco, alcohol, and/or recreational drugs.
  • You will have a physical exam, including measurement of your weight, height, and vital signs (blood pressure, breathing rate, temperature, and heart rate).
  • You will be asked how well you are able to perform the normal activities of daily living (performance status).
  • You will have an x-ray, computed tomography (CT) scan, magnetic resonance imaging (MRI), and/or positron emission tomography (PET)/CT to check the status of the disease.
  • Blood (about 2 teaspoons) will be drawn for routine tests. This routine blood draw will include a pregnancy test for women who are able to have children. To take part in this study, the pregnancy test must be negative.

The study doctor will discuss the screening test results with you. If the screening tests show that you are not eligible to take part in the study, you will not be enrolled. Other options will be discussed with you.

Study Drug Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of sirolimus and vorinostat based on when you joined this study. Up to 8 dose levels of sirolimus and vorinostat will be tested. Three (3) to 9 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level of the study drug combination. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the combination of sirolimus and vorinostat is found.

Once the highest tolerated dose of the combination of sirolimus and vorinostat is found, up to 14 participants with the tumor type that is most likely to respond to the study drug combination will receive the study drugs at that dose level.

Study Drug Administration:

Each study "cycle" is 28 days.

Everyday, you will take sirolimus by mouth 1 time a day. You should take it at about the same time each day with food and a cup (8 ounces) of water.

On Day 8 of Cycle 1, you will start taking vorinostat by mouth 1 time a day. You should take it at about the same time each day with food and a cup (8 ounces) of water.

Once you start taking vorinostat, you will take both drugs everyday while you are on study, unless told otherwise by your doctor.

Study Visits:

At every study visit, you will be asked about any current health conditions you have, drugs you may be taking, and if you have had any side effects.

About Days 8 and 22 of Cycle 1:

  • You will have a physical exam.
  • Blood (about 2 teaspoons) will be drawn for routine tests.

About Day 15 of Cycle 1, blood (about 2 teaspoons) will be drawn for routine tests.

About Day 22 of Cycles 2 and beyond:

  • You will have a physical exam.
  • Blood (about 2 teaspoons) will be drawn for routine tests.

Every 4 weeks, a routine blood draw will include a pregnancy test for women who are able to become pregnant.

Every 8 weeks, you will have an x-ray, CT scan, MRI, and/or PET/CT to check the status of the disease. If the study doctor thinks it is needed, they will be performed more often.

Length of Study:

You may continue taking the study drugs for as long as you are benefitting. You will be taken off study if you experience intolerable side effects, the study doctor thinks it is in your best interest, or the disease gets worse.

Additional Information:

  • You should not drink grapefruit juice or eat grapefruit products while on study.
  • You should not take any herbal drugs.
  • You must tell the study doctor about any drugs you take (prescription or over-the-counter).
  • You should tell the study doctor about any changes in how you are feeling or about any problems you have during the study.

This is an investigational study. Sirolimus is FDA approved and commercially available as an anti-rejection drug for kidney transplant recipients. Vorinostat is FDA approved and commercially available for the treatment of cutaneous T-cell lymphoma. The combination of these drugs is investigational.

Up to 65 patients will take part in this study. All will be enrolled at M. D. Anderson.

Open or close this module Conditions
Conditions: Advanced Cancer
Keywords: Sirolimus
Rapamune
mTOR Inhibitor
Histone Deacetylase Inhibitor
Vorinostat
SAHA
Suberoylanilide Hydroxamic Acid
MSK-390
Zolinza
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 65 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Sirolimus + Vorinostat Drug: Sirolimus
Starting oral dose level 1 mg daily on Days 1-28
Other Names:
  • 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
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Maximum Tolerated Dose (MTD)
[ Time Frame: Every 28 day cycle ]

Open or close this module Eligibility
Minimum Age:
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

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 >/= 75000uL, 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 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 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
  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
Open or close this module Contacts/Locations
Central Contact Person: Razelle Kurzrock, MD, BS
Telephone: 713-794-1226
Study Officials: Razelle Kurzrock, MD, BS
Study Chair
UT MD Anderson Cancer Center
Locations: United States, Texas
UT MD Anderson Cancer Center
[Recruiting]
Houston, Texas, United States, 77030
Contact:Principal Investigator: Razelle Kurzrock, MD
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links: Description: UT MD Anderson Cancer Center website
Available IPD/Information:

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