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


Phase 1
N/A
N/A
Open (Enrolling)
Both
Advanced Cancer

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Trial Information

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


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.

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 9 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 7 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, you will have a blood (about 1 teaspoon) drawn or urine collected for a
pregnancy test if you 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.

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 107 patients will take part in this study. All will be enrolled at M. D. Anderson.


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 absence of Gilbert's syndrome, ALT present, creatinine
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 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

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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome Time Frame:

Every 28 day cycle

Safety Issue:

Yes

Principal Investigator

Filip Janku, MD, PHD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2009-0729

NCT ID:

NCT01087554

Start Date:

March 2010

Completion Date:

Related Keywords:

  • Advanced Cancer
  • Sirolimus
  • Rapamune
  • mTOR Inhibitor
  • Histone Deacetylase Inhibitor
  • Vorinostat
  • SAHA
  • Suberoylanilide Hydroxamic Acid
  • MSK-390
  • Zolinza
  • Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030