Clinical Trials /

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

NCT01552434

Description:

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 Conditions:
  • Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 2012-0061
  • SECONDARY ID: NCI-2012-00347
  • SECONDARY ID: 2012-0061
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT01552434

Conditions

  • 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

Interventions

DrugSynonymsArms
BevacizumabAnti-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-VEGFGroup I (temsirolimus, bevacizumab, cetuximab)
CetuximabCetuximab Biosimilar CMAB009, Chimeric Anti-EGFR Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225, Erbitux, IMC-C225Group I (temsirolimus, bevacizumab, cetuximab)
TemsirolimusCCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog, Rapamycin Analog CCI-779, ToriselGroup I (temsirolimus, bevacizumab, cetuximab)
Valproic AcidDepakene, Stavzor, ValproateGroup II (temsirolimus, bevacizumab, valproic acid)

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. 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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Group I (temsirolimus, bevacizumab, cetuximab)ExperimentalPatients 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.
  • Bevacizumab
  • Cetuximab
  • Temsirolimus
Group II (temsirolimus, bevacizumab, valproic acid)ExperimentalPatients 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.
  • Bevacizumab
  • Temsirolimus
  • Valproic Acid
Group III (temsirolimus, bevacizumab)ExperimentalPatients receive temsirolimus and bevacizumab as in Group I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Bevacizumab
  • Temsirolimus

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure:Levels of surrogate anti-angiogenesis markers
Time Frame:Up to week 4 of course 1
Safety Issue:
Description:Correlated with anti-tumor activity.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Temsirolimus
  • CCI-779
  • Torisel
  • Bevacizumab
  • Avastin
  • rhuMAb-VEGF
  • Anti-VEGF Monoclonal Antibody
  • Advanced Cancers
  • Advanced Malignancy
  • Metastatic
  • cancer
  • Cetuximab
  • C225
  • Erbitux
  • IMC-C225
  • Valproic Acid

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