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

M.D. Anderson Cancer Center logo

M.D. Anderson Cancer Center

Status and phase

Active, not recruiting
Phase 1

Conditions

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

Treatments

Biological: Bevacizumab
Drug: Valproic Acid
Biological: Cetuximab
Other: Pharmacological Study
Drug: Temsirolimus
Other: Laboratory Biomarker Analysis

Study type

Interventional

Funder types

Other
NIH

Identifiers

NCT01552434
2012-0061 (Other Identifier)
NCI-2012-00347 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

155 patients

Sex

All

Volunteers

No Healthy Volunteers

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 design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

155 participants in 3 patient groups

Group I (temsirolimus, bevacizumab, cetuximab)
Experimental group
Description:
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.
Treatment:
Other: Laboratory Biomarker Analysis
Drug: Temsirolimus
Other: Pharmacological Study
Biological: Cetuximab
Biological: Bevacizumab
Group II (temsirolimus, bevacizumab, valproic acid)
Experimental group
Description:
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.
Treatment:
Other: Laboratory Biomarker Analysis
Drug: Temsirolimus
Other: Pharmacological Study
Drug: Valproic Acid
Biological: Bevacizumab
Group III (temsirolimus, bevacizumab)
Experimental group
Description:
Patients receive temsirolimus and bevacizumab as in Group I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Treatment:
Other: Laboratory Biomarker Analysis
Drug: Temsirolimus
Other: Pharmacological Study
Biological: Bevacizumab

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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