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Bevacizumab, Temsirolimus, Valproic Acid, Cetuximab

Information source: M.D. Anderson Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Advanced Cancers

Intervention: Temsirolimus (Drug); Bevacizumab (Drug); Valproic Acid (Drug); Cetuximab (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Sarina Piha-Paul, MD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center

Overall contact:
Sarina Piha-Paul, MD, Phone: 713-563-1930

Summary

The goal of this clinical research study is to find the highest tolerable dose of Avastin (bevacizumab) and Torisel (temsirolimus) that can be given in combination with either valproic acid or cetuximab to patients with advanced cancer that is refractory. The safety of this drug combination will also be studied. Bevacizumab is designed to block the growth of blood vessels, which may help to slow or block the growth of cancer. Temsirolimus is designed to block the growth of cancer cells, which may cause cancer cells to die. Valproic acid is an anti-seizure drug that may be able to activate tumor-fighting genes, causing cancer cells to die. Cetuximab is designed to block a certain protein, called EGFR, that is thought to cause cancer cells to grow. This may cause cancer cells to die.

Clinical Details

Official title: A Phase I Trial of Bevacizumab, Temsirolimus Alone and in Combination With Valproic Acid or Cetuximab in Patients With Advanced Malignancy

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Maximum Tolerated Dose (MTD) of Bevacizumab and Temsirolimus and/or Cetuximab or Valproic Acid

Secondary outcome: Tumor Response

Detailed description: 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.

Eligibility

Minimum age: N/A. Maximum age: N/A. Gender(s): Both.

Criteria:

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 complete response of at least 10% or improves survival by at least three months. In addition, patients with diseases that are "benign" by pathology, but relentlessly progressive, leading to disability, pain, and premature death in the majority of cases (including but not limited to lymphangioleiomyomatosis (LAM), type 2 neurofibromatosis (NF), Erdheim Chester disease, and Castleman's disease) may also be considered for enrollment 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 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.

Locations and Contacts

Sarina Piha-Paul, MD, Phone: 713-563-1930

University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Additional Information

University of Texas MD Anderson Cancer Center Website

Starting date: March 2012
Last updated: April 23, 2015

Page last updated: August 23, 2015

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