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Trial record 12 of 211 for:    Oral Cancer | Recruiting Studies | NIH

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

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ClinicalTrials.gov Identifier: NCT01552434
Recruitment Status : Recruiting
First Posted : March 13, 2012
Last Update Posted : September 17, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
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. Monoclonal antibodies, such as bevacizumab and cetuximab, 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.

Condition or disease Intervention/treatment Phase
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 Biological: Bevacizumab Biological: Cetuximab Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Temsirolimus Drug: Valproic Acid Phase 1

Detailed 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 216 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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 and Other Indications
Actual Study Start Date : March 16, 2012
Estimated Primary Completion Date : March 31, 2020
Estimated Study Completion Date : March 31, 2021


Arm Intervention/treatment
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.
Biological: Bevacizumab
Given IV
Other Names:
  • 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

Biological: Cetuximab
Given IV
Other Names:
  • Cetuximab Biosimilar CMAB009
  • Chimeric Anti-EGFR Monoclonal Antibody
  • Chimeric MoAb C225
  • Chimeric Monoclonal Antibody C225
  • Erbitux
  • IMC-C225

Other: Laboratory Biomarker Analysis
Optional correlative studies

Other: Pharmacological Study
Optional correlative studies

Drug: Temsirolimus
Given IV
Other Names:
  • CCI-779
  • CCI-779 Rapamycin Analog
  • Cell Cycle Inhibitor 779
  • Rapamycin Analog
  • Rapamycin Analog CCI-779
  • Torisel

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.
Biological: Bevacizumab
Given IV
Other Names:
  • 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

Other: Laboratory Biomarker Analysis
Optional correlative studies

Other: Pharmacological Study
Optional correlative studies

Drug: Temsirolimus
Given IV
Other Names:
  • CCI-779
  • CCI-779 Rapamycin Analog
  • Cell Cycle Inhibitor 779
  • Rapamycin Analog
  • Rapamycin Analog CCI-779
  • Torisel

Drug: Valproic Acid
Given PO
Other Names:
  • Depakene
  • Stavzor
  • Valproate

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
Other Names:
  • 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

Other: Laboratory Biomarker Analysis
Optional correlative studies

Other: Pharmacological Study
Optional correlative studies

Drug: Temsirolimus
Given IV
Other Names:
  • CCI-779
  • CCI-779 Rapamycin Analog
  • Cell Cycle Inhibitor 779
  • Rapamycin Analog
  • Rapamycin Analog CCI-779
  • Torisel




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) of bevacizumab, defined as the dose level below the dose at which 2 of 6 patients experience drug-related dose limiting toxicity (DLT) [ Time Frame: 4 weeks ]
    Graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

  2. MTD of temsirolimus, defined as the dose level below the dose at which 2 of 6 patients experience DLT [ Time Frame: 4 weeks ]
    Graded by the NCI CTCAE version 3.0.


Secondary Outcome Measures :
  1. Anti-tumor efficacy of each combination (objective response by Response Evaluation Criteria In Solid Tumors [RECIST] and World Health Organization [WHO] criteria) [ Time Frame: Up to 6 years ]
  2. Levels of surrogate anti-angiogenesis markers [ Time Frame: Up to week 4 of course 1 ]
    Correlated with anti-tumor activity.


Other Outcome Measures:
  1. Tissue microvascular parameters [ Time Frame: Up to week 4 of course 1 ]
    For the parameters, an exploratory analysis of change from baseline will be conducted which will include mean, median, standard deviation, and 95% confidence limits.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01552434


Contacts
Contact: Sarina Piha-Paul 713-563-1930 spihapau@mdanderson.org

Locations
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Sarina A. Piha-Paul    713-563-1930      
Principal Investigator: Sarina A. Piha-Paul         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Sarina Piha-Paul M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01552434     History of Changes
Other Study ID Numbers: 2012-0061
NCI-2012-00347 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2012-0061 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: March 13, 2012    Key Record Dates
Last Update Posted: September 17, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancers
Advanced Malignancy
cancer
Temsirolimus
CCI-779
Torisel
Bevacizumab
Avastin
rhuMAb-VEGF
Anti-VEGF Monoclonal Antibody
Metastatic
Cetuximab
C225
Erbitux
IMC-C225
Valproic Acid

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms, Second Primary
Thoracic Neoplasms
Thyroid Neoplasms
Respiratory Tract Neoplasms
Genital Neoplasms, Female
Soft Tissue Neoplasms
Pharyngeal Neoplasms
Endocrine Gland Neoplasms
Genital Neoplasms, Male
Lip Neoplasms
Urologic Neoplasms
Neoplasms, Mesothelial
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Connective and Soft Tissue
Nerve Sheath Neoplasms
Neoplasms, Nerve Tissue
Neoplastic Syndromes, Hereditary
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Lymphatic Vessel Tumors
Perivascular Epithelioid Cell Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Otorhinolaryngologic Neoplasms
Cranial Nerve Neoplasms