Bevacizumab and Temsirolimus Alone or in Combination With Valproic Acid or Cetuximab in Treating Patients With Advanced or Metastatic Malignancy or Other Benign Disease

Study Purpose

This phase I trial studies the side effects and best dose of bevacizumab and temsirolimus alone or in combination with valproic acid or cetuximab in treating patients with a malignancy that has spread to other places in the body or other disease that is not cancerous. Immunotherapy with bevacizumab and cetuximab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as valproic acid, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether bevacizumab and temsirolimus work better when given alone or with valproic acid or cetuximab in treating patients with a malignancy or other disease that is not cancerous.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.

An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.

Searching Both is inclusive of interventional and observational studies.

Eligible Ages N/A and Over
Gender All
More Inclusion & Exclusion Criteria

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 complete response of at least 10% or improves survival by at least three months; in addition, patients with disease 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.
  • - 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.
  • - Eastern Cooperative Oncology Group (ECOG) performance status =< 2.
  • - Karnofsky >= 60% - Lansky performance status of >= 60% for participants 16 years old or younger.
  • - Absolute neutrophil count >= 1,000/mL.
  • - Platelets >= 50,000/mL.
  • - Creatinine =< 3 X upper limit of normal (ULN) - Total bilirubin =< 3.0.
  • - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 X ULN.
  • - Fasting level of total cholesterol of no more than 350 mg/dL.
  • - Triglyceride level of no more than 400 mg/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 cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inducers and/or inhibitors; 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 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation (for the arm combining bevacizumab, temsirolimus and cetuximab) - Patients who have had major surgery within 6 weeks of enrollment in the study

Trial Details

Trial ID:

This trial id was obtained from, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.


Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

M.D. Anderson Cancer Center
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Sarina A Piha-Paul
Principal Investigator Affiliation M.D. Anderson Cancer Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Overall Status Recruiting
Countries United States

The disease, disorder, syndrome, illness, or injury that is being studied.

Advanced Malignant Neoplasm, Castleman Disease, Digestive System Carcinoma, Erdheim-Chester Disease, Lip and Oral Cavity Carcinoma, Lymphangioleiomyomatosis, Malignant Endocrine Neoplasm, Malignant Female Reproductive System Neoplasm, Malignant Male Reproductive System Neoplasm, Malignant Neoplasm, Malignant Respiratory Tract Neoplasm, Malignant Thoracic Neoplasm, Malignant Urinary System Neoplasm, Mesothelial Neoplasm, Metastatic Malignant Neoplasm, Metastatic Urothelial Carcinoma, Neurofibromatosis Type 2, Recurrent Adult Soft Tissue Sarcoma, Recurrent Breast Carcinoma, Recurrent Childhood Soft Tissue Sarcoma, Recurrent Digestive System Carcinoma, Recurrent Female Reproductive System Carcinoma, Recurrent Male Reproductive System Carcinoma, Recurrent Malignant Neoplasm, Recurrent Pharyngeal Carcinoma, Recurrent Thyroid Gland Carcinoma, Refractory Malignant Neoplasm, Soft Tissue Neoplasm, Stage III Breast Cancer AJCC v7, Stage III Pharyngeal Cancer, Stage IIIA Breast Cancer AJCC v7, Stage IIIB Breast Cancer AJCC v7, Stage IIIC Breast Cancer AJCC v7, Stage IV Breast Cancer AJCC v6 and v7, Stage IV Pharyngeal Cancer, Stage IVA Pharyngeal Cancer, Stage IVB Pharyngeal Cancer, Stage IVC Pharyngeal Cancer, Thyroid Gland Neoplasm
Study Website: View Trial Website
Additional Details


  • I. To determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of treatment with bevacizumab and temsirolimus in combination and plus valproic acid or cetuximab.
  • I. Preliminary descriptive assessment of anti-tumor efficacy of each combination.
  • II. Preliminary assessment of the pharmacokinetic, pharmacodynamic markers of target inhibition and correlates of response (optional).
OUTLINE: This is a dose-escalation study of bevacizumab and temsirolimus. Patients are assigned to 1 of 3 treatment groups. GROUP I: Patients receive temsirolimus intravenously (IV) over 30-60 minutes on days 1, 8, 15, and 22; bevacizumab IV over 30-90 minutes on days 1 and 15; and cetuximab IV over 1-2 hours on days 1, 8, 15, and 22. GROUP II: Patients receive temsirolimus and bevacizumab as in Group I and valproic acid orally (PO) daily on days 1-7 and 15-21. GROUP III: Patients receive temsirolimus and bevacizumab as in Group
  • I. In all groups, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Arms & Interventions


Experimental: Group I (temsirolimus, bevacizumab, cetuximab)

Patients receive temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22; bevacizumab IV over 30-90 minutes on days 1 and 15; and cetuximab IV over 60-120 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Experimental: Group II (temsirolimus, bevacizumab, valproic acid)

Patients receive temsirolimus and bevacizumab as in Group I and valproic acid PO on days 1-7 and 15-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Experimental: Group III (temsirolimus, bevacizumab)

Patients receive temsirolimus and bevacizumab as in Group I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.


Biological: - Bevacizumab

Given IV

Biological: - Cetuximab

Given IV

Other: - Laboratory Biomarker Analysis

Optional correlative studies

Other: - Pharmacological Study

Optional correlative studies

Drug: - Temsirolimus

Given IV

Drug: - Valproic Acid

Given PO

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

M D Anderson Cancer Center, Houston, Texas




M D Anderson Cancer Center

Houston, Texas, 77030

Site Contact

Sarina A. Piha-Paul


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