Bevacizumab, Temsirolimus, Valproic Acid, Cetuximab
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Advanced Cancers |
Drug: Temsirolimus Drug: Bevacizumab Drug: Valproic Acid Drug: Cetuximab |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I Trial of Bevacizumab, Temsirolimus Alone and in Combination With Valproic Acid or Cetuximab in Patients With Advanced Malignancy |
- Maximum Tolerated Dose (MTD) [ Time Frame: 56 days ] [ Designated as safety issue: Yes ]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.
- Tumor Response [ Time Frame: After two 28 day cycles. ] [ Designated as safety issue: No ]Tumor response defined as one or more of the following: (1) stable disease for more than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by RECIST criteria, (3) decrease in tumor markers by more than or equal to 25% (for example, a >/= 25% decrease in CA125 for patients with ovarian cancer), or (4) a partial response according to Choi criteria, i.e. decrease in size by 10% or more, or a decrease in tumor density, as measured in Hounsfield units (HU), by more than or equal to 15% (28).
| Estimated Enrollment: | 216 |
| Study Start Date: | March 2012 |
| Estimated Primary Completion Date: | March 2020 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Temsirolimus + Bevacizumab + Cetuximab
Dose Escalation Group: Starting dose of Temsirolimus 5 mg by vein on Days 1, 8, 15, and 22 of each 28 day cycle. Starting dose of Bevacizumab 2.5 mg/kg by vein on Days 1 and 15 of each 28 day cycle. Starting dose of Cetuximab loading dose 100 mg/m2, and maintenance dose 75 mg/m2 by vein on Days 1, 8, 15, and 22 of each 28 day cycle. Dose Expansion Group Starting dose: Maximum tolerated dose (MTD) from Dose Escalation Group. |
Drug: Temsirolimus
Dose Escalation Group: Starting dose of Temsirolimus 5 mg by vein on Days 1, 8, 15, and 22 of each 28 day cycle. Dose Expansion Group Starting dose: Maximum tolerated dose (MTD) from Dose Escalation Group. Other Names:
Drug: Bevacizumab
Starting dose of Bevacizumab 2.5 mg/kg by vein on Days 1 and 15 of each 28 day cycle. Dose Expansion Group Starting dose: Maximum tolerated dose (MTD) from Dose Escalation Group. Other Names:
Drug: Cetuximab
Starting dose of Cetuximab loading dose 100 mg/m2, and maintenance dose 75 mg/m2 by vein on Days 1, 8, 15, and 22 of each 28 day cycle. Dose Expansion Group Starting dose: Maximum tolerated dose (MTD) from Dose Escalation Group. Other Names:
|
|
Experimental: Temsirolimus + Bevacizumab + Valproic Acid
Dose Escalation Group: Starting dose of Temsirolimus 5 mg by vein on Days 1, 8, 15, and 22 of each 28 day cycle. Starting dose of Bevacizumab 2.5 mg/kg by vein on Days 1 and 15 of each 28 day cycle. Starting dose of Valproic Acid 5 mg/kg rounded to nearest 250 mg by mouth on Days 1 - 7 and 15 - 21 of each 28 day cycle. Dose Expansion Group Starting dose: Maximum tolerated dose (MTD) from Dose Escalation Group. |
Drug: Temsirolimus
Dose Escalation Group: Starting dose of Temsirolimus 5 mg by vein on Days 1, 8, 15, and 22 of each 28 day cycle. Dose Expansion Group Starting dose: Maximum tolerated dose (MTD) from Dose Escalation Group. Other Names:
Drug: Bevacizumab
Starting dose of Bevacizumab 2.5 mg/kg by vein on Days 1 and 15 of each 28 day cycle. Dose Expansion Group Starting dose: Maximum tolerated dose (MTD) from Dose Escalation Group. Other Names:
Drug: Valproic Acid
Starting dose of Valproic Acid 5 mg/kg rounded to nearest 250 mg by mouth on Days 1 - 7 and 15 - 21 of each 28 day cycle. Dose Expansion Group Starting dose: Maximum tolerated dose (MTD) from Dose Escalation Group Other Name: Depakene
|
|
Experimental: Temsirolimus + Bevacizumab
Dose Escalation Group: Starting dose of Temsirolimus 5 mg by vein on Days 1, 8, 15, and 22 of each 28 day cycle. Starting dose of Bevacizumab 2.5 mg/kg by vein on Days 1 and 15 of each 28 day cycle. Dose Expansion Group Starting dose: Maximum tolerated dose (MTD) from Dose Escalation Group. |
Drug: Temsirolimus
Dose Escalation Group: Starting dose of Temsirolimus 5 mg by vein on Days 1, 8, 15, and 22 of each 28 day cycle. Dose Expansion Group Starting dose: Maximum tolerated dose (MTD) from Dose Escalation Group. Other Names:
Drug: Bevacizumab
Starting dose of Bevacizumab 2.5 mg/kg by vein on Days 1 and 15 of each 28 day cycle. Dose Expansion Group Starting dose: Maximum tolerated dose (MTD) from Dose Escalation Group. Other Names:
|
Show Detailed Description Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
- 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.
- ECOG performance status </= 2 (Karnofsky >/= 60%).
- Lansky performance status of >/= 60% for participants 16 years old or younger.
- Patients must have allowable organ and marrow function defined as: absolute neutrophil count >/= 1,000/mL; platelets >/=50,000/mL; creatinine </= 3 X ULN; total bilirubin </= 3.0; AST(SGOT)/ALT(SGPT) </= 5 X ULN; fasting level of total cholesterol of no more than 350mg/dL; triglyceride level of no more than 400mg/dL.
- 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.
- Ability to understand and the willingness to sign a written informed consent document.
- Patients may not be receiving any other investigational agents and/or any other concurrent anticancer agents or therapies.
Exclusion Criteria:
- Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.
- Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg on medication).
- 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
- Pregnant or breast-feeding women.
- History of hypersensitivity to bevacizumab, murine products, or any component of the formulation.
- History of hypersensitivity to Temsirolimus or its metabolites (including sirolimus), polysorbate 80, or to any component of the formulation.
- History of hypersensitivity to cetuximab, murine products, or any component of the formulation.
- 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.
- Colorectal cancer patients with known KRAS mutation (for the arm combining bevacizumab, temsirolimus and cetuximab)
- Patients who have had major surgery within 6 weeks of enrollment in the study.
Contacts and Locations| Contact: Sarina Piha-Paul, MD | 713-794-4225 |
| United States, Texas | |
| UT MD Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
| Principal Investigator: | Sarina Piha-Paul, MD | UT MD Anderson Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01552434 History of Changes |
| Other Study ID Numbers: | 2012-0061 |
| Study First Received: | March 7, 2012 |
| Last Updated: | December 10, 2012 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by M.D. Anderson Cancer Center:
|
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 |
Additional relevant MeSH terms:
|
Neoplasms Antibodies Antibodies, Monoclonal Sirolimus Everolimus Valproic Acid Bevacizumab Cetuximab Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Anticonvulsants Central Nervous System Agents Therapeutic Uses Enzyme Inhibitors |
Molecular Mechanisms of Pharmacological Action GABA Agents Neurotransmitter Agents Antimanic Agents Tranquilizing Agents Central Nervous System Depressants Psychotropic Drugs Antibiotics, Antineoplastic Antineoplastic Agents Antifungal Agents Anti-Infective Agents Immunosuppressive Agents Anti-Bacterial Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents |
ClinicalTrials.gov processed this record on May 16, 2013