A Phase I Trial of Bevacizumab, Temsirolimus Alone and in Combination With Valproic Acid or Cetuximab in Patients With Advanced Malignancy
N/A
N/A
Both
Advanced Cancers
Trial Information
A Phase I Trial of Bevacizumab, Temsirolimus Alone and in Combination With Valproic Acid or Cetuximab in Patients With Advanced Malignancy
Study Groups:
If you are found to be eligible, you will be assigned to a study drug combination that the
study doctor thinks is in your best interest:
- Drug Combination 1: Temsirolimus, bevacizumab, and cetuximab
- Drug Combination 2: Temsirolimus, bevacizumab, and valproic acid
- Drug Combination 3: Temsirolimus and bevacizumab
Dose Escalation Group:
You will be assigned to a dose level of your study drug combination based on when you joined
this study.
Up to 11 dose levels will be tested for Study Drug Combination 1. Up to 10 dose levels will
be tested for Study Drug Combinations 2 and 3. Three (3) participants will be enrolled at
each dose level of each combination. 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 study drug combination is found.
Dose Expansion Group:
After the highest tolerable dose is found, up to an additional 10 participants, called the
"dose expansion group," will receive each study drug combination at that dose.
Study Drug Administration:
The study drugs will be given in cycles. Cycles will be about 28 days or longer, depending
on any side effects you may have.
You will be given bevacizumab by vein on Days 1 and 15 of each cycle. On Day 1 of Cycle 1,
you will receive it over 90 minutes. If you tolerate it well in Cycle 1, you will receive
it over 60 minutes in Cycle 2. If you then tolerate it well in Cycle 2, you will receive it
over 30 minutes in Cycle 3. As long as you still tolerate it well, you will receive it over
30 minutes in Cycle 4 and further cycles.
You will be given temsirolimus by vein on Days 1, 8, 15, and 22 of each cycle. During Day 1
of Cycle 1, you will receive it over 60 minutes. If you tolerate it well on Day 1 of Cycle
1, it will be given over 30 minutes for all future doses, as long you continue to tolerate
it well.
If you are taking Drug Combination 1, you will be given cetuximab by vein 1 time every week.
The first time you receive cetuximab, it will be given over 2 hours. Every time you
receive cetuximab after that, it will be given over 1 hour.
If you are taking Drug Combination 2, you will take valproic acid by mouth 1 time each day
in each cycle. The drug can be taken with or without food.
Study Visits:
One (1) time each week during Cycle 1, the following tests and procedures will be performed:
- You will have a physical exam, including measurement of your weight and vital signs.
- Blood (about 1 tablespoon) will be collected for routine tests.
- Urine will be collected for routine tests only during the first week of Cycle 1.
Every 4 weeks during Cycles 2 and beyond:
- You will have a physical exam, including measurement of your weight and vital signs.
- Blood (about 1 tablespoon) and urine will be collected for routine tests.
After Cycle 2, you will have a CT or MRI scan after every 2 cycles to check the status of
the disease.
Length of Study:
You may continue taking the study drug combination for as long as the doctor thinks it is in
your best interest. You will no longer be able to take the study drugs if the disease gets
worse, if intolerable side effects occur, or if you are unable to follow study directions.
This is an investigational study. Bevacizumab is FDA approved and commercially available
for the treatment of colorectal cancer and a type of lung cancer. Temsirolimus is FDA
approved and commercially available for the treatment of kidney cancer that has spread.
Cetuximab is FDA approved and commercially available for the treatment of colorectal cancer
and a type of head and neck cancer. Valproic acid is FDA approved and commercially
available to help control seizures.
The combination of bevacizumab and temsirolimus is not FDA approved to treat advanced
cancer. The combination of bevacizumab and temsirolimus with cetuximab or valproic acid is
not FDA approved to treat advanced cancer. At this time, each study drug combination is
being used for research only.
Up to 216 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 therapy,
relapsed after standard therapy, or have no standard therapy that induces a CR
(Complete Response) rate of at least 10% or improves survival by at least three
months.
2. Patients should be at least four weeks from the last day of therapeutic radiation or
cytotoxic chemotherapy or from antibody therapy, or at least five half-lives from
non-cytotoxic targeted or biologic therapy. Patients may have received palliative
radiation immediately before (or during) treatment provided radiation is not to the
only target lesion available.
3. ECOG performance status /= 60%).
4. Lansky performance status of >/= 60% for participants 16 years old or younger.
5. Patients must have allowable organ and marrow function defined as: absolute
neutrophil count >/= 1,000/mL; platelets >/=50,000/mL; creatinine bilirubin cholesterol of no more than 350mg/dL; triglyceride level of no more than 400mg/dL.
6. Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 90 days after the last dose.
7. Ability to understand and the willingness to sign a written informed consent
document.
8. Patients may not be receiving any other investigational agents and/or any other
concurrent anticancer agents or therapies.
Exclusion Criteria:
1. Patients with clinically significant unexplained bleeding within 28 days prior to
entering the study.
2. Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg,
diastolic blood pressure > 90 mmHg on medication).
3. Patients with clinically significant cardiovascular disease: History of CVA
(cerebrovascular accident) within 6 months, Myocardial infarction or unstable angina
within 6 months, Unstable angina pectoris
4. Pregnant or breast-feeding women.
5. History of hypersensitivity to bevacizumab, murine products, or any component of the
formulation.
6. History of hypersensitivity to Temsirolimus or its metabolites (including sirolimus),
polysorbate 80, or to any component of the formulation.
7. History of hypersensitivity to cetuximab, murine products, or any component of the
formulation.
8. Patients that are taking CYP3A4 inducers and/or inhibitors. Please see section "Drug
Information" for details. If a patient has a history of taking CYP3A4 inducers and/or
inhibitors prior to enrollment on the protocol, it is strongly recommended that the
patient stops the drug and waits at least 5 half-lives of said drug before initiating
therapy on protocol.
9. Colorectal cancer patients with known KRAS mutation (for the arm combining
bevacizumab, temsirolimus and cetuximab)
10. Patients who have had major surgery within 6 weeks of enrollment in the study.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum Tolerated Dose (MTD)
Outcome Description:
MTD defined as dose level below dose at which 2 of 6 patients experience drug-related dose limiting toxicity (DLT) in first cycle. DLT defined as any grade 3 or 4 non-hematologic toxicity as defined in NCI CTC v3.0, any Grade 4 hematologic toxicity lasting 2 weeks or longer, any Grade 4 nausea or vomiting > 5 days despite maximum anti-nausea regimens, and any other Grade 3 non-hematologic toxicity including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in the NCI-CTCAE that is attributable to therapy.
Outcome Time Frame:
56 days
Safety Issue:
Yes
Principal Investigator
Sarina Piha-Paul, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
UT MD Anderson Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
2012-0061
NCT ID:
NCT01552434
Start Date:
March 2012
Completion Date:
Related Keywords:
- Advanced Cancers
- Advanced Cancers
- Advanced Malignancy
- Metastatic cancer
- Temsirolimus
- CCI-779
- Torisel
- Bevacizumab
- Avastin
- rhuMAb-VEGF
- Anti-VEGF Monoclonal Antibody
- Cetuximab
- C225
- Erbitux
- IMC-C225
- Valproic Acid
- Depakene
- Neoplasms
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
