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 Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

155 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-03-16

Study Completion Date

2026-03-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Bevacizumab and Temsirolimus in Patients With Advanced Malignancy

NCT00610493

Advanced Cancer

COMPLETED PHASE1

Bevacizumab and Temsirolimus in Treating Patients With Recurrent or Persistent Endometrial Cancer

NCT00723255

Recurrent Endometrial Carcinoma

COMPLETED PHASE2

Bevacizumab in Combination With Temozolomide in Patients With Neuroendocrine Tumors

NCT00137774

Neuroendocrine Tumors

COMPLETED PHASE2

Bevacizumab in Treating Patients With Relapsed or Refractory Multiple Myeloma

NCT00482495

Multiple Myeloma and Plasma Cell Neoplasm

COMPLETED PHASE2

TORC1/2 Inhibitor MLN0128 and Bevacizumab in Treating Patients With Recurrent Glioblastoma or Advanced Solid Tumors

NCT02142803

Adult Glioblastoma Endometrial Clear Cell Adenocarcinoma Endometrial Serous Adenocarcinoma +21 more

ACTIVE_NOT_RECRUITING PHASE1

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

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 Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type BIOLOGICAL

Given IV

Cetuximab

Intervention Type BIOLOGICAL

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Optional correlative studies

Pharmacological Study

Intervention Type OTHER

Optional correlative studies

Temsirolimus

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type BIOLOGICAL

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Optional correlative studies

Pharmacological Study

Intervention Type OTHER

Optional correlative studies

Temsirolimus

Intervention Type DRUG

Given IV

Valproic Acid

Intervention Type DRUG

Given PO

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.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type BIOLOGICAL

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Optional correlative studies

Pharmacological Study

Intervention Type OTHER

Optional correlative studies

Temsirolimus

Intervention Type DRUG

Given IV

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Bevacizumab

Given IV

Intervention Type BIOLOGICAL

Cetuximab

Given IV

Intervention Type BIOLOGICAL

Laboratory Biomarker Analysis

Optional correlative studies

Intervention Type OTHER

Pharmacological Study

Optional correlative studies

Intervention Type OTHER

Temsirolimus

Given IV

Intervention Type DRUG

Valproic Acid

Given PO

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Anti-VEGF Anti-VEGF Humanized Monoclonal Antibody Anti-VEGF rhuMAb Avastin Bevacizumab Biosimilar BEVZ92 Bevacizumab Biosimilar BI 695502 Bevacizumab Biosimilar CBT 124 Bevacizumab Biosimilar FKB238 Bevacizumab Biosimilar MIL60 Bevacizumab Biosimilar QL 1101 BEVACIZUMAB, LICENSE HOLDER UNSPECIFIED Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer Recombinant Humanized Anti-VEGF Monoclonal Antibody rhuMab-VEGF Cetuximab Biosimilar CMAB009 Chimeric Anti-EGFR Monoclonal Antibody Chimeric MoAb C225 Chimeric Monoclonal Antibody C225 Erbitux IMC-C225 CCI-779 CCI-779 Rapamycin Analog Cell Cycle Inhibitor 779 Rapamycin Analog Rapamycin Analog CCI-779 Torisel Depakene Stavzor Valproate

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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

Eligible Sex

ALL

Accepts Healthy Volunteers

No