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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma; Malignant Glioma; Gliosarcoma; Glioblastoma With Primitive Neuronal Component; Oligodendroglial Component Present
• Intervention / Treatment: Drug: Plerixafor; Drug: Temozolomide; Radiation: Whole-Brain Radiotherapy (WBRT); Radiation: Radiation Therapy

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford Cancer Institute Palo Alto

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy; 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.

Drug: Plerixafor; Plerixafor will be administered via infusion at 400 micrograms per kilogram per day for four weeks beginning one week before the end of radiation; Other Names: Mozobil; AMD 3100; JM-3100; SDZ SID 791; Drug: Temozolomide; 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.; Other Names: Temodar; SCH 52365; Temodal; Temcad; Methazolastone; RP-46161; Temomedac; 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; Radiation: Whole-Brain Radiotherapy (WBRT); Undergo Whole brain radiotherapy (WBRT) - Radiotherapy consists of 30 Gy in 15 fractions of whole brain radiations; Other Names: WBRT; whole-brain radiation therapy; whole-brain radiotherapy; Radiation: Radiation Therapy; Radiotherapy consists of 30 Gy in 15 fractions; Other Names: RT; XRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	32 months
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.	30 days
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	5 years

Collaborators and Investigators

• Sponsor: Lawrence D Recht
• Collaborators: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2018
• Primary Completion (Anticipated): January 26, 2024
• Study Completion (Anticipated): July 1, 2027

Study Registration Dates

• First Submitted: November 7, 2018
• First Submitted That Met QC Criteria: November 14, 2018
• First Posted (Actual): November 19, 2018

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Glioma; Gliosarcoma; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide; Plerixafor
• Other Study ID Numbers: IRB-46410 (Other Identifier: Stanford IRB); NCI-2018-02159 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); BRN0037 (Other Identifier: OnCore Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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