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Trial of Temozolomide, Bevacizumab Plus Bortezomib for Recurrent Glioblastoma Multiforme

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Emory University
Sponsor:
Information provided by (Responsible Party):
Jeffrey James Olson, Emory University
ClinicalTrials.gov Identifier:
NCT01435395
First received: September 14, 2011
Last updated: June 18, 2014
Last verified: June 2014
  Purpose

This is a single-center (Emory University), open-label, single arm, phase I study to assess safety and toxicity of bortezomib in combination with bevacizumab and escalating doses of temozolomide for patients with recurrent glioblastoma multiforme. Patients requiring anti-epileptic medications will have to be at least 10 days off EIAEDs. Only non-EIAEDs are accepted.


Condition Intervention Phase
Glioblastoma Multiforme
Drug: Temozolomide, bevacizumab and bortezomib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: WCI1837-10: Phase I Trial of Temozolomide, Bevacizumab Plus Bortezomib for Patients With Recurrent Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Determination of progressive disease,Complete or partial responses [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    Complete or partial responses will be based upon major changes in tumor size on the Gd-MRI scan compared to the baseline scan. Determination of progressive disease is based upon comparison to the previous scan with the smallest measurements.


Secondary Outcome Measures:
  • Assess the time to progression [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    six month progression free survival and overall survival of patients completing one cycle of the investigational therapy


Estimated Enrollment: 18
Study Start Date: December 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Therapy
Therapy with temozolomide, bevacizumab and bortezamib
Drug: Temozolomide, bevacizumab and bortezomib
Escalating temozolomide with standard dose bevacizumab and bortezomib

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Each patient must meet all of the following inclusion criteria to be enrolled in the study:

    1. Age 18 years or more.
    2. Patients must have histologically confirmed diagnosis of a recurrent/progressive WHO grade IV malignant gliomas (glioblastoma multiforme and gliosarcoma).
    3. Patients must have measurable progressive or recurrent disease by MRI within 2 weeks of starting treatment.
    4. No prior bortezomib is allowed.
    5. An interval of at least 6 weeks between prior surgical resection, 4 weeks from the end of prior radiotherapy.
    6. Patients must be at least 10 days off any Enzyme inducing Anti-Epileptic Drugs (EIAEDs) of the CYP-450 such as phenytoin, carbamazepine, phenobarbital.
    7. Karnofsky performance status score of 60 or mre, and a MMSE > 15.
    8. Patients must have recovered from toxicity of prior therapy.
    9. Hematocrit > 29%, ANC > 1,500 cells/microliter, platelets > 125,000 cells/microliter for 14 days prior to enrollment.
    10. Serum creatinine < 1.5 mg/dl, serum SGOT and bilirubin < 1.5 times upper limit of normal.
    11. An interval of at least 3 months from the completion of most recent radiation therapy. At least 4 weeks from a non-nitrosourea chemotherapy regimen and at least 6 weeks from a nitrosourea containing regimen.
    12. For patients on corticosteroids, they must have been on a stable dose for 1 week prior to entry if clinically recommended.
    13. May have up to three biological therapies
    14. Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
    15. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
    16. Male subject agrees to use an acceptable method for contraception for the duration of the study.

Exclusion Criteria:

  • Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

    1. Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids.
    2. Greater than three prior recurrences.
    3. Enzyme inducing Anti-Epileptic Drugs (EIAEDs) of the CYP-450 such as phenytoin, carbamazepine, phenobarbital.
    4. Patients receiving concurrent investigational drugs.
    5. Evidence of CNS hemorrhage on baseline MRI or CT scan (except for grade 1 hemorrhage that has been stable for at least 3 months).
    6. History of stroke within six months.
    7. Requires therapeutic anti-coagulation.
    8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics and psychiatric illness/social situations that would limit compliance with study requirements, or disorders associated with significant immunocompromised state.
    9. Patient has a calculated or measured creatinine clearance of <20 mL/minute within 14 days before enrollment.
    10. Patient has greater or equal to Grade 2 peripheral neuropathy within 14 days before enrollment.
    11. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (Appendix), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
    12. Patient has hypersensitivity to bortezomib, boron or mannitol.
    13. Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
    14. Patient has received other investigational drugs with 14 days before enrollment
    15. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
    16. Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy. Patients with prior malignancies must be disease free for at least 5 years.
    17. Serious, non-healing wound, active ulcer, or untreated bone fracture. Bone fractures must be healed.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01435395

Contacts
Contact: Katarzyna Kopcewicz 404-778-2981 kkopcew@emory.edu

Locations
United States, Georgia
Emory University Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Jeffrey Olson    404-778-5770      
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Jeffrey J Olson, MD Emory University
  More Information

No publications provided

Responsible Party: Jeffrey James Olson, MD, Emory University
ClinicalTrials.gov Identifier: NCT01435395     History of Changes
Other Study ID Numbers: IRB00014595, WCII1837-10
Study First Received: September 14, 2011
Last Updated: June 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Emory University:
Single-center, open-label, single arm, phase I study to assess safety and toxicity of bortezomib in combination with bevacizumab and temozolomide
Patients requiring anti-epileptic medications will have to be at least 10 days off EIAEDs.
Only non-EIAEDs are accepted

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Bevacizumab
Bortezomib
Dacarbazine
Temozolomide
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014