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

Phase 2

Active, not recruiting

Conditions: Glioblastoma With Primitive Neuronal Component
Glioblastoma
Gliosarcoma
Oligodendroglial Component Present
Malignant Glioma

Interventions: Drug: Plerixafor
Drug: Temozolomide
Radiation: Whole-Brain Radiotherapy (WBRT)
Radiation: Radiation Therapy

Registration Number: NCT03746080

Lead Sponsor: Lawrence D Recht

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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 21

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy	Radiation Therapy	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.
Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy	Whole-Brain Radiotherapy (WBRT)	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.
Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy	Plerixafor	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.
Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy	Temozolomide	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.

Primary Outcome Measures

Name	Time	Method
Proportion of Progression Free Survival Participants (PFS) at Six Months	6 months	Proportion of 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

Name	Time	Method
Median Survival	up to 31 months	Median survival will be assessed at 31 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	30 days	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. The number of participants experiencing adverse events, including qualifying dose limiting toxicities (DLTs) will be tabulated by attribution (Unrelated, Unlikely to be related, Definitely related) and severity.
Patterns of Treatment Failure	5 years	Patterns of Failure in patients receiving Whole Brain Radiotherapy + Plerixafor + Chemoradiotherapy was assessed by determining the out-of-field occurrence or occurrence outside of the brain over time. Local treatment failure was defined as within the 95% isodose region. Out-of-field occurrence is defined by any treatment failure observed outside treatment area.