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Whole Brain Radiation Therapy With Standard Temozolomide Chemo-Radiotherapy and Plerixafor in Treating Patients With Glioblastoma

Primary Purpose

Glioblastoma, Glioblastoma With Primitive Neuronal Component, Gliosarcoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Plerixafor
Temozolomide
Whole-Brain Radiotherapy (WBRT)
Radiation Therapy
Sponsored by
Lawrence D Recht
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have tissue confirmation of high grade (World Health Organization (WHO) grade IV) glioma including but not limited to glioblastoma, gliosarcoma, glioblastoma with oligodendroglial features, glioblastoma with primitive neuroectodermal tumor (PNET) features.
  • The patient must have post-operative contrast enhanced imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) unless only biopsy performed. For patients having biopsy alone, post-operative imaging is not routinely obtained and therefore the preoperative study will serve as baseline.
  • Patient should have surgery (biopsy, partial resection or gross total resection) and no additional anti-cancer therapy except the chemo-radiation as specified in the protocol.
  • Patients must have Karnofsky performance score >= 60.
  • Absolute neutrophil count (ANC) >= 1500 (at time of screening).
  • Platelets >= 100,000 ml (at time of screening).
  • Serum creatinine =< 1.5mg/dl (at time of screening).
  • Creatinine (Cr) clearance should be > 50 mL/min (at time of screening).
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 times the upper limit of normal (at time of screening).
  • If female of childbearing potential, negative pregnancy test (at time of screening).
  • The patient or his/her legal representative must have the ability to understand and willingness to sign a written informed consent document.
  • Patient agrees to use an effective method of contraception (hormonal or two barrier methods) while on study and for at least 3 months following the plerixafor infusion.

Exclusion Criteria:

  • Prior or concurrent treatment with Avastin (bevacizumab).
  • Prior exposure to plerixafor.
  • Prior use of other investigational agents to treat the brain tumor.
  • Recent history of myocardial infarct (less than 3 months) or history of active angina.
  • Prior malignancy except for non-melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 3 years prior to 1st dose of investigational drug.
  • Prior sensitivity to plerixafor.
  • Pregnant or patients who are breastfeeding.

Sites / Locations

  • Stanford Cancer Institute Palo AltoRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy

Arm Description

After completion maximal safe surgical resection, patients undergo radiation therapy for 42 days, initiating whole brain radiation therapy at day 21 (dose 16 of radiation therapy) and receive temozolomide daily on days 1 to 42. Beginning 7 days before the completion of whole brain radiation therapy, patients receive plerixafor by continuous infusion on days to 1 to 28. Beginning 1 week after completion of plerixafor infusion and 35 days after completion of whole brain radiation therapy, patients receive temozolomide monthly for 6 to 12 courses in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Progression-free survival (PFS) at six months
Progression free survival will be measured at 6 months post initiation of chemoradiation. Simon 2-stage design will be use to assess progression-free survival. Will be computed from start of induction therapy and summarized with Kaplan-Meier estimates.

Secondary Outcome Measures

Median Survival
Median survival will be assessed at 32 months of subjects who have completed the 28 day Plerixafor infusion. Will be computed from start of induction therapy and summarized with Kaplan-Meier estimates.
Toxicity associated with Plerixafor/WBRT
Incidence of adverse events will be graded and recorded per Common Terminology Criteria for Adverse Events version 5.0. Will assess reported toxicities up until 30 days of treatment. Adverse events and qualifying dose limiting toxicities (DLTs) will be tabulated by cohort, site and severity.
Patterns of treatment failure
Will assess pattern of failure (out-of-field occurrence or occurrence outside of the brain) over time. Local treatment failure is defined as within the 95% isodose region

Full Information

First Posted
November 7, 2018
Last Updated
April 13, 2023
Sponsor
Lawrence D Recht
Collaborators
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT03746080
Brief Title
Whole Brain Radiation Therapy With Standard Temozolomide Chemo-Radiotherapy and Plerixafor in Treating Patients With Glioblastoma
Official Title
A Follow-Up Study to Add Whole Brain Radiotherapy (WBRT) to Standard Temozolomide Chemo-Radiotherapy in Newly Diagnosed Glioblastoma (GBM) Treated With 4 Weeks of Continuous Infusion Plerixafor
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 4, 2018 (Actual)
Primary Completion Date
January 26, 2024 (Anticipated)
Study Completion Date
July 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Lawrence D Recht
Collaborators
Sanofi

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial studies how well whole brain radiation therapy works with standard temozolomide chemo-radiotherapy and plerixafor in treating patients with glioblastoma (brain tumor). Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as temozolomide, 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. Plerixafor is a drug that may prevent recurrence of glioblastoma after radiation treatment. Giving whole brain radiation therapy with standard temozolomide chemo-radiotherapy and plerixafor may work better in treating patients with glioblastoma.
Detailed Description
PRIMARY OBJECTIVES: I. The primary purpose of this Phase II study is to evaluate the efficacy of Plerixafor administered with a modified radiation regimen that includes a component of WBRT. The primary endpoint is 6-month progression free survival post initiation of Chemoradiation. SECONDARY OBJECTIVES: I. To assess the median survival of patients treated with continuous infusion plerixafor/WBRT. II. To assess the toxicities both short and long term of continuous infusion plerixafor/WBRT. III. To assess the patterns of failure (in and out of irradiated brain field, out of brain) of continuous infusion plerixafor/WBRT. OUTLINE: After completion maximal safe surgical resection, patients undergo radiation therapy for 42 days, initiating whole brain radiation therapy at day 21 (dose 16 of radiation therapy) and receive temozolomide daily on days 1-42. Beginning 7 days before the completion of whole brain radiation therapy, patients receive plerixafor by continuous infusion on days 1-28. Beginning 1 week after completion of plerixafor infusion and 35 days after completion of whole brain radiation therapy, patients receive temozolomide monthly for 6-12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for adverse events for 30 days after the last dose of Plerixafor and then every 12 weeks for 5 years for survival follow-up.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Glioblastoma With Primitive Neuronal Component, Gliosarcoma, Malignant Glioma, Oligodendroglial Component Present

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy
Arm Type
Experimental
Arm Description
After completion maximal safe surgical resection, patients undergo radiation therapy for 42 days, initiating whole brain radiation therapy at day 21 (dose 16 of radiation therapy) and receive temozolomide daily on days 1 to 42. Beginning 7 days before the completion of whole brain radiation therapy, patients receive plerixafor by continuous infusion on days to 1 to 28. Beginning 1 week after completion of plerixafor infusion and 35 days after completion of whole brain radiation therapy, patients receive temozolomide monthly for 6 to 12 courses in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Plerixafor
Other Intervention Name(s)
AMD 3100, JM-3100, Mozobil, SDZ SID 791
Intervention Description
Plerixafor will be administered via infusion at 400 micrograms per kilogram per day for four weeks beginning one week before the end of radiation
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Other Intervention Name(s)
CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac
Intervention Description
Temozolomide (TMZ) will be administered concurrently with the radiation for 42 days and 6-12 cycles of monthly adjuvant Temozolomide (TMZ) after completion of Plerixafor infusion.
Intervention Type
Radiation
Intervention Name(s)
Whole-Brain Radiotherapy (WBRT)
Other Intervention Name(s)
WBRT, whole-brain radiation therapy, whole-brain radiotherapy
Intervention Description
Undergo Whole brain radiotherapy (WBRT) - Radiotherapy consists of 30 Gy in 15 fractions of whole brain radiations
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy
Other Intervention Name(s)
XRT, RT
Intervention Description
Radiotherapy consists of 30 Gy in 15 fractions
Primary Outcome Measure Information:
Title
Progression-free survival (PFS) at six months
Description
Progression free survival will be measured at 6 months post initiation of chemoradiation. Simon 2-stage design will be use to assess progression-free survival. Will be computed from start of induction therapy and summarized with Kaplan-Meier estimates.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Median Survival
Description
Median survival will be assessed at 32 months of subjects who have completed the 28 day Plerixafor infusion. Will be computed from start of induction therapy and summarized with Kaplan-Meier estimates.
Time Frame
32 months
Title
Toxicity associated with Plerixafor/WBRT
Description
Incidence of adverse events will be graded and recorded per Common Terminology Criteria for Adverse Events version 5.0. Will assess reported toxicities up until 30 days of treatment. Adverse events and qualifying dose limiting toxicities (DLTs) will be tabulated by cohort, site and severity.
Time Frame
30 days
Title
Patterns of treatment failure
Description
Will assess pattern of failure (out-of-field occurrence or occurrence outside of the brain) over time. Local treatment failure is defined as within the 95% isodose region
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have tissue confirmation of high grade (World Health Organization (WHO) grade IV) glioma including but not limited to glioblastoma, gliosarcoma, glioblastoma with oligodendroglial features, glioblastoma with primitive neuroectodermal tumor (PNET) features. The patient must have post-operative contrast enhanced imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) unless only biopsy performed. For patients having biopsy alone, post-operative imaging is not routinely obtained and therefore the preoperative study will serve as baseline. Patient should have surgery (biopsy, partial resection or gross total resection) and no additional anti-cancer therapy except the chemo-radiation as specified in the protocol. Patients must have Karnofsky performance score >= 60. Absolute neutrophil count (ANC) >= 1500 (at time of screening). Platelets >= 100,000 ml (at time of screening). Serum creatinine =< 1.5mg/dl (at time of screening). Creatinine (Cr) clearance should be > 50 mL/min (at time of screening). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 times the upper limit of normal (at time of screening). If female of childbearing potential, negative pregnancy test (at time of screening). The patient or his/her legal representative must have the ability to understand and willingness to sign a written informed consent document. Patient agrees to use an effective method of contraception (hormonal or two barrier methods) while on study and for at least 3 months following the plerixafor infusion. Exclusion Criteria: Prior or concurrent treatment with Avastin (bevacizumab). Prior exposure to plerixafor. Prior use of other investigational agents to treat the brain tumor. Recent history of myocardial infarct (less than 3 months) or history of active angina. Prior malignancy except for non-melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 3 years prior to 1st dose of investigational drug. Prior sensitivity to plerixafor. Pregnant or patients who are breastfeeding.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hari Priya Yerraballa
Phone
6507249363
Email
yhpriya@stanford.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Sophie Bertrand
Phone
650-723-4467
Email
sophieb@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lawrence Recht
Organizational Affiliation
Stanford Cancer Institute Palo Alto
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford Cancer Institute Palo Alto
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lawrence Recht
Phone
650-725-8630
Email
lrecht@stanford.edu
First Name & Middle Initial & Last Name & Degree
Lawrence Recht

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Whole Brain Radiation Therapy With Standard Temozolomide Chemo-Radiotherapy and Plerixafor in Treating Patients With Glioblastoma

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