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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

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

NCT ID

NCT03746080

First Posted

November 7, 2018

Last Updated

April 13, 2023

Sponsor

Lawrence D Recht

Collaborators

Sanofi

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

Product Manufactured in and Exported from the U.S.

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

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

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Median Survival

Description

Time Frame

32 months

Title

Toxicity associated with Plerixafor/WBRT

Description

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

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

yhpriya@stanford.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Sophie Bertrand

Phone

650-723-4467

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

lrecht@stanford.edu

First Name & Middle Initial & Last Name & Degree

Lawrence Recht

12. IPD Sharing Statement

Plan to Share IPD

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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