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Efficacy of Hypofractionated XRT w/Bev. + Temozolomide for Recurrent Gliomas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01478321
Recruitment Status : Terminated (Slow accrual to some cohorts)
First Posted : November 23, 2011
Results First Posted : March 12, 2020
Last Update Posted : March 12, 2020
Sponsor:
Information provided by (Responsible Party):
Northwestern University

Tracking Information
First Submitted Date  ICMJE November 17, 2011
First Posted Date  ICMJE November 23, 2011
Results First Submitted Date  ICMJE January 30, 2020
Results First Posted Date  ICMJE March 12, 2020
Last Update Posted Date March 12, 2020
Actual Study Start Date  ICMJE December 14, 2011
Actual Primary Completion Date September 12, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 27, 2020)
Overall Survival (OS) for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab. [ Time Frame: From treatment initiation and every 8 weeks for up to 53.5 months ]
Data will be analyzed using Kaplan-Meier curves. OS is defined as the time from first re-irradiation treatment until death from any cause.
Original Primary Outcome Measures  ICMJE
 (submitted: November 21, 2011)
OS [ Time Frame: Every 2 months or up to 90 days ]
Data will be analyzed using Kaplan-Meier curves. Defined as the time from first re-irradiation treatment until death from any cause.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 27, 2020)
  • Patient Reported Quality of Life (QOL) [ Time Frame: Completed before treatment (baseline) after Cycle 1 (approximately week 15) and Cycle 2 (approximately week 23)of adjuvant treatment and at the end of treatment (up to 7 cycles of adjuvant treatment, where 1 cycle =8 weeks) ]
    Questionnaires were completed before treatment (baseline) at the end of treatment (EOT) and after Cycle 1 and Cycle 2 of treatment (Initial phase of treatment =5 weeks + approximately 2 weeks recovery then adjuvant therapy where 1 cycle = 8 weeks). The following questionnaires were completed by patients to evaluate quality of life (QOL) at these timepoints: FACT-Fatigue - scores from 1 to 4 with 1=not at all and 4=very much, the higher the score the more fatigue reported by the patient. FACT-Brain (FACT Br) which included - Physcial Well-being (PWB), Social/Family Well-being (SWB), Emotional Well-being (EWB), and Functional Well-being (FWB). Patients gave scores from 0 to 4 with 0=not at all and 4=very much, the higher the score the better the QOL reported by the patient.
  • Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab [ Time Frame: Completed weekly during initial phase of 5 weeks and 2 weeks recovery, then every cycle during adjuvant therapy where 1 cycle =8 weeks (for up to 7 cycles) ]
    Toxicity will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria on Day 1 of every treatment cycle and by patient report while on study treatment and up to 30 days after the last treatment. Grade 1 - 4 adverse events (AE) where the relationship between the AE and at least one of the study drugs were considered to be definite, probable or possible, were collected and graded as: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
  • Percentage of Patients With Progression Free Survival (PFS) at 6 Months and 12 Months [ Time Frame: At 6 and 12 months after the start of treatment ]
    Progression Free Survival is defined as the time from the first study treatment to the first occurrence of disease progression or death. Data will be analyzed using Kaplan-Meier curves. Tumor measurements and assessments will be based on Updated Response Assessment Criteria of High Grade Gliomas- Neuro-Oncology Working Group (RANO criteria). Tumor assessments may include either a CT or MRI scan of the brain, however the same method should be used throughout the treatment period for each patient. In general, progressive disease is defined as any of the following: ≥ 25% increase in T1 gadolinium enhancing disease, increase in T2/Flair, new lesions present or decrease in clinical status
Original Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2011)
  • Change in neurological status [ Time Frame: Baseline, weekly during radiation therapy, monthly during adjuvant phase, and then every 2 months or up to 90 days post-treatment ]
    Determined by examinations, patient-reported outcomes, and performance status.
  • Safety profile [ Time Frame: Baseline, weekly during radiation therapy, and prior to each course ]
    Assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria.
  • PFS [ Time Frame: At 3, 6, and 12 months ]
    Defined as the time from the first study treatment to the first occurrence of disease progression or death. Data will be analyzed using Kaplan-Meier curves.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Hypofractionated XRT w/Bev. + Temozolomide for Recurrent Gliomas
Official Title  ICMJE A Phase II Study of the Efficacy of Hypofractionated Radiation Therapy With Bevacizumab and Temozolomide Followed by Maintenance Temozolomide and Bevacizumab for Recurrent High-Grade Gliomas
Brief Summary This phase II trial studies how well giving hypofractionated radiation therapy together with temozolomide and bevacizumab works in treating patients with high-grade glioblastoma multiforme or anaplastic glioma. Specialized radiation therapy, such as hypofractionated radiation therapy, that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving hypofractionated radiation therapy together with temozolomide and bevacizumab may kill more tumor cells.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine the overall survival (OS) for patients with recurrent high grade malignant gliomas treated with concurrent radiation, temozolomide, and bevacizumab followed by adjuvant temozolomide and bevacizumab.

SECONDARY OBJECTIVES:

I. Determine the impact of this regimen on neurologic symptoms via Functional Assessment of Cancer Therapy-Brain (FACT-Br) and FACT-Fatigue scales and Eastern Cooperative Oncology Group (ECOG) performance status.

II. Determine the safety profile of this regimen. III. Determine the progression free survival (PFS) at 6 and 12 months (all patients) as well as at 3 months (bevacizumab-exposed patients only).

OUTLINE:

CONCURRENT THERAPY: Patients undergo hypofractionated radiation therapy 5 days a week beginning on day 0. Patients also receive temozolomide orally (PO) once daily (QD) and bevacizumab intravenously (IV) over 30-90 minutes once every 2 weeks beginning on days -3 to 0. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity.

ADJUVANT THERAPY: Beginning 2 weeks after completion of radiation therapy, patients receive temozolomide PO QD for 6 weeks and bevacizumab IV over 30-90 minutes once every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2-3 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Adult Anaplastic Astrocytoma
  • Adult Anaplastic Ependymoma
  • Adult Anaplastic Oligodendroglioma
  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
Intervention  ICMJE
  • Drug: Temozolomide
    Given PO
    Other Name: TMZ
  • Radiation: hypofractionated radiation therapy
    Undergo hypofractionated radiation therapy
  • Biological: bevacizumab
    Given IV
    Other Name: anti-VEGF humanized monoclonal antibody,
  • Other: questionnaire administration
    Ancillary studies
Study Arms  ICMJE Experimental: Treatment (radiation, chemotherapy, monoclonal antibody)

CONCURRENT THERAPY: Patients undergo hypofractionated radiation therapy 5 days a week beginning on day 0. Patients also receive temozolomide PO QD and bevacizumab IV over 30-90 minutes once every 2 weeks beginning on days -3 to 0. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity.

ADJUVANT THERAPY: Beginning 2 weeks after completion of radiation therapy, patients receive temozolomide PO QD for 6 weeks and bevacizumab IV over 30-90 minutes once every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

Interventions:
  • Drug: Temozolomide
  • Radiation: hypofractionated radiation therapy
  • Biological: bevacizumab
  • Other: questionnaire administration
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 27, 2020)
54
Original Estimated Enrollment  ICMJE
 (submitted: November 21, 2011)
80
Actual Study Completion Date  ICMJE September 12, 2018
Actual Primary Completion Date September 12, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must have histologically confirmed diagnosis of glioblastoma multiforme (GBM) or anaplastic glioma, World Health Organization (WHO) grade 3 or 4

    • Patients must have measurable or non-measurable (evaluable) disease recurrence
    • Recurrence must be documented based on a combination of clinical and imaging parameters, consistent with routine clinical practice, with or without histologic confirmation
    • Patients may have had any number of relapses and be eligible for the study
    • Patients must have been previously treated with radiation therapy and temozolomide (bevacizumab-naïve - Groups 1 and 3) or radiation therapy, temozolomide and bevacizumab (bevacizumab-exposed -Groups 2 and 4); therapy with these agents may be given together or sequentially in the past
    • All patients may have had prior surgery, chemotherapy, and radiation therapy; prior biologic therapy is permitted only for bevacizumab-exposed patients (Groups 2 and 4); prior treatment with Gliadel is permitted for all groups
    • For bevacizumab-naïve patients (Groups 1 and 3) a minimum of 6 months must have elapsed since completion of radiation therapy for study entry, and there is no minimum time since completion of last chemotherapy; for bevacizumab-exposed patients (Groups 2 and 4) no minimum time since completion of last radiation therapy, biologic agents, or chemotherapy will be required for study entry
    • Patients must have an ECOG performance status of =< 2
    • Hemoglobin >= 10
    • Platelets >= 100,000/mm^3
    • Absolute neutrophil count >= 1500/mm^3
    • Bilirubin =< 1.5 x upper limit of normal range (ULN)
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN
    • Blood urea nitrogen (BUN) =< 1.5 x ULN
    • Creatinine =< 1.5 x ULN
    • Urine protein/creatinine ratio should be =< 1
    • Patients' baseline blood pressure must be adequately controlled with or without antihypertensive medications prior to enrollment (systolic < 140 mmHg, diastolic < 90 mmHg)
    • Patients must have a baseline evaluation including history and physical examination with neurological evaluation and magnetic resonance imaging (MRI) of the brain (with and without gadolinium-based contrast), all completed within 30 days prior to initiation of treatment
    • Female patients of child-bearing potential must have a negative pregnancy test within 14 days prior to enrollment on study; child-bearing potential is defined as any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets one of the following criteria:

      • Has not undergone a hysterectomy or bilateral oophorectomy
      • Or has not been naturally postmenopausal for at least 12 consecutive months (i.e. has had menses at any time in the preceding consecutive 12 months)
    • Females of child-bearing potential and sexually-active males must consent to follow acceptable birth control methods to avoid contraception while on treatment
    • All subjects must have given signed, informed consent prior to registration on study
    • Patients previously treated outside of Northwestern must have their pathology slides sent to Northwestern for review and confirmation - NOTE: a copy of the pathology report is sufficient for registration

Exclusion Criteria:

  • • Patients who are pregnant or breast-feeding will NOT be eligible for participation

    • Patients with a prior malignancy will NOT be eligible for participation aside from the following exception:

  • Patients who have had any curatively treated malignancy and have been disease free without treatment for 1 year prior to study entry ARE eligible for participation

    • Patients with an active second malignancy (other than non-melanoma skin cancer or cervical cancer in situ) are NOT eligible for participation
    • Patients with uncontrolled hypertension (>= 140/90 mmHg) are NOT eligible for participation
    • Patients who exhibit any other serious concurrent infection or other medical illness which would jeopardize their ability to receive the therapy outlined in this protocol with reasonable safety will NOT be eligible for participation
    • The eligibility criteria listed above are interpreted literally and cannot be waived
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01478321
Other Study ID Numbers  ICMJE NU 11C02
STU00053636 ( Other Identifier: Northwestern University IRB )
NCI CTRP# ( Other Identifier: NCI-2011-02904 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Northwestern University
Study Sponsor  ICMJE Northwestern University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jeffrey Raizer, MD Northwestern University
PRS Account Northwestern University
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP