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Phase I Study of Temsirolimus in Combination With Metformin in Patients With Advanced Cancers


Phase 1
14 Years
N/A
Open (Enrolling)
Both
Advanced Cancers

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Trial Information

Phase I Study of Temsirolimus in Combination With Metformin in Patients With Advanced Cancers


Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose
level of temsirolimus and metformin based on when you join this study. Up to 6 dose levels
of temsirolimus and metformin will be tested. Up to 6 participants will be enrolled at each
dose level. The first group of participants will receive the lowest dose level. 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
temsirolimus and metformin is found.

When the highest tolerable dose or most appropriate combination dose level is found, 14 more
participants will take the study drugs at this dose level.

Study Drug Administration:

Each study cycle is 28 days. Before you start taking both drugs in Cycle 1, you will take
metformin only for 2 weeks. This is called a titration period.

On Days 1, 8, 15, and 21 of each cycle, you will receive temsirolimus by vein over 30-60
minutes.

Before you receive temsirolimus, you will receive Benadryl (diphenhydramine) by vein over
30-60 minutes to help lower the risk of allergic reactions.

You will take metformin by mouth every day at about the same time each day with a meal and
cup of water (about 8 ounces). You should take it at home except on the days when you have a
study visit. Depending on your dose, you may take metformin 1-3times daily. Your study
doctor will tell you how to take this drug.

You will be given a letter to take to your home doctor(s) about your study drug
administration as part of your care provided outside of MD Anderson.

Study Visits:

At every study visit, you will be asked about your health, any other drugs you are taking,
and if you have had any side effects.

Exams and tests will be performed before you receive the study drugs that day. Cycle 1 Week
1 tests and exams may not have to be repeated if done within 7 days.

During Week 1 of the titration period:

- You will have a physical exam, including measurement of your weight and vital signs.

- Your performance status will be recorded.

- Blood (about 2 teaspoons) will be drawn for routine tests.

- During Week 1 only, urine will be collected for routine tests.

During Week 2 of the titration period:

-Blood (about 2 teaspoons) will be drawn for routine tests.

During Weeks 1 and 3 of Cycle 1:

- You will have a physical exam, including measurement of your weight and vital signs.

- Your performance status will be recorded.

- Blood (about 2 teaspoons) will be drawn for routine tests.

- During Week 1 only, urine will be collected for routine tests.

During Weeks 2 and 4 of Cycle 1, blood (about 2 teaspoons) will be drawn for routine tests.

During Week 1 of Cycles 2 and beyond:

- You will have a physical exam, including measurement of your weight and vital signs.

- Your performance status will be recorded.

- Blood (about 2 teaspoons) and urine will be collected for routine tests.

During Week 3 of Cycles 2 and beyond, blood (about 2 teaspoons) will be drawn for routine
tests.

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

After about 6 months (about 6 cycles) of taking the study drugs, you will have the CT scan
or MRI scan every 2-4 cycles if your study doctor thinks it is needed.

Length of Study Participation:

You may continue taking the study drugs for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drug if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over when you have completed the end-of-study visit.

End-of-Study Visit:

Within 30 days after your last dose of study drugs, you will return to the clinic. The
following tests and procedures will be performed:

- You will have a physical exam, including measurement of your weight and vital signs.

- Your performance status will be recorded.

- Blood (about 2 teaspoons) and urine will be collected for routine tests.

This is an investigational study. Temsirolimus is FDA approved and commercially available
for the treatment of renal cell carcinoma. Metformin is FDA approved and commercially
available for the treatment of diabetes mellitus. The combination of these drugs to treat
advanced cancer is investigational.

Up to 64 patients will take part in this study. All will be enrolled at MD Anderson.


Inclusion Criteria:



1. Patients with advanced or metastatic cancer that is refractory to standard therapies,
who have relapsed after standard therapy, or whose cancers have no standard therapy
that induces a complete response (CR) rate of at least 10% or improves survival by at
least three months.

2. Patients must have evaluable or measurable disease by RECIST criteria.

3. Patients must be >/= 4 weeks beyond treatment of any chemotherapy, other
investigational therapy, hormonal, biological, targeted agents or radiotherapy, and
must have recovered to Patients may have received palliative low dose radiotherapy to the limbs 1-4 weeks
before this therapy provided pelvis, sternum, scapulae, vertebrae, or skull were not
included in the radiotherapy field. Patients who have received non-chemotherapeutic
biological agents will need to wait at least 5 half-lives or 4 wks, whichever is
shorter, from the last day of treatment.

4. Patients must be >/= 4 weeks beyond treatment with metformin and currently not taking
metformin

5. Patients may be on antidiabetic treatment other than Metformin

6. ECOG performance status
7. Abnormal organ function is permitted. However, patients must have absolute neutrophil
count >/= 1000/mL; platelets >/= 75,000/mL; creatinine < 1.5 mg/dl in males and < 1.4
in females;T. Bilirubin ALT(SGPT)
8. Women of child-bearing potential MUST have a negative serum or urine HCG test unless
prior hysterectomy or menopause (defined as 12 consecutive months without menstrual
activity). Patients should not become pregnant or breastfeed while on this study.
Sexually active patients must agree to use contraception prior to study entry, for
the duration of study participation, and for 30 days after the last dose

9. Ability to understand and willingness to sign a written informed consent document.

10. Patients must be >/= 14 years of age.

11. Patients in the expansion cohort must have any diagnosed molecular aberrations that
activate the PI3K/mTOR or MEK pathways, including but not limited to alterations in
one or more of the following genes: PTEN, BRAF, KRAS, NRAS, PI3KCA, ErbB1, ErbB2,
MET, RET, c-KIT GNAQ, GNA11 and ALK.

Exclusion Criteria:

1. Patients who are pregnant or breastfeeding.

2. Uncontrolled intercurrent illness including, but not limited to, active infection
requiring hospitalization.

3. History of hypersensitivity to temsirolimus or metformin.

4. History of CVA, myocardial infarction or unstable angina within the previous six
months before starting therapy

5. New York Heart Association Class III or greater congestive heart failure.

6. Patients with major surgery within 30 days prior to entering the study.

7. Patients unable to swallow oral medications or with pre-existing gastrointestinal
disorders that might interfere with proper absorption of oral drugs.

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) of Temsirolimus and Metformin

Outcome Description:

MTD defined as highest dose studied in which incidence of dose limiting toxicity (DLT) less than 33%. DLTs defined as adverse events (AEs) related to study agents which occur during first cycle of treatment. Toxicity must have possible, probable or definite attribution to study drugs.

Outcome Time Frame:

10 weeks

Safety Issue:

Yes

Principal Investigator

Aung Naing, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2011-0923

NCT ID:

NCT01529593

Start Date:

March 2012

Completion Date:

Related Keywords:

  • Advanced Cancers
  • Advanced Cancers
  • Metastatic cancer
  • Tumor response
  • Dose limiting toxicity
  • DLT
  • Maximum tolerated dose
  • MTD
  • Temsirolimus
  • CCI-779
  • Torisel
  • Metformin
  • Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030