Plerixafor After Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed High Grade Glioma

Phase 1

Completed

• Conditions: Adult Gliosarcoma; Adult Medulloblastoma; Adult Ependymoblastoma; Adult Giant Cell Glioblastoma; Adult Mixed Glioma; Adult Pineoblastoma; Adult Glioblastoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Adult Oligodendroglial Tumors
• Interventions: Radiation: radiation therapy; Drug: temozolomide; Drug: plerixafor; Other: laboratory biomarker analysis; Other: pharmacological study

• Registration Number: NCT01977677
• Lead Sponsor: Lawrence Recht

Brief Summary

This pilot phase I/II trial studies the side effects and best dose of plerixafor after radiation therapy and temozolomide and to see how well it works in treating patients with newly diagnosed high grade glioma. Plerixafor may stop the growth of tumor cells by blocking blood flow to the tumor. 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. Radiation therapy uses high energy x rays to kill tumor cells. Giving plerixafor after radiation therapy and temozolomide may be an effective treatment for high grade glioma.

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the safety of using continuous infusion Plerixafor subsequent to irradiation in patients with newly diagnosed glioblastoma multiforme (GBM).

II. To assess the efficacy of Plerixafor as measured by progression free survival at 6 months (PFS6) from the start of irradiation.

OUTLINE: This is a phase I, dose-escalation study of plerixafor followed by a phase II study.

Within 4 weeks of surgery, patients undergo radiation therapy and receive temozolomide orally (PO) over 42 days. Beginning 8 days prior to completion of chemoradiotherapy, patients receive plerixafor intravenously (IV) continuously for 2-4 weeks. Patients also receive temozolomide PO 5 days a month beginning 35 days after completion of radiation therapy.

After completion of study treatment, patients are followed up every 12 weeks for 5 years.

Study Timeline

• Study First Submitted: 2013-10-31
• Study First Submitted QC: 2013-11-06
• Study First Posted: 2013-11-07
• Study Start: 2014-11
• Primary Completion: 2017-11
• Results First Submitted: 2018-06-05
• Results First Submitted QC: 2018-06-05
• Results First Posted: 2018-07-03
• Status Verified: 2018-09
• Study Completion: 2018-09
• Last Update Submitted: 2018-09-27
• Last Update Posted: 2018-10-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Patients must have tissue confirmation of high grade (WHO Grade IV) glioma including but not limited to glioblastoma, gliosarcoma, glioblastoma with oligodendroglial features, glioblastoma with PNET features.

• The patient must have post-operative contrast enhanced imaging (CT or MRI) unless only biopsy performed (in which case post-operative imaging is not routinely obtained. In these patients, 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 chemoradiation as specified in the protocol.

• For those patients in which steroids are clinically indicated, there must be a stable or decreasing dose of steroid medication for ≥ one week prior to the start of infusion.

• Patients must be between the ages of 18 and 75 years old.

• Patients must have Karnofsky Performance score ≥ 60.

• Adequate organ function is needed at time of screening visit including:

  • ANC ≥ 1500
  • Platelets ≥ 100,000 ml
  • Serum Creatinine ≤ 1.5mg/dl; Cr Clearance should be >50 mL/min
  • AST and ALT ≤ 3 times the upper limit of normal
  • If female of childbearing potential, negative pregnancy test

• 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 or arrhythmia
• Prior malignancy except previously diagnosed and definitively treated more than 3 years prior to trial or whose prognosis is deemed good enough to not warrant surveillance
• Prior sensitivity to Plerixafor
• Pregnant or patients who are breastfeeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (radiation therapy, temozolomide, plerixafor)	temozolomide	Within 4 weeks of surgery, patients undergo radiation therapy and receive temozolomide PO over 42 days. Beginning 8 days prior to completion of chemoradiotherapy, patients receive plerixafor IV continuously for 2-4 weeks. Patients also receive temozolomide PO 5 days a month beginning 35 days after completion of radiation therapy.
Treatment (radiation therapy, temozolomide, plerixafor)	radiation therapy	Within 4 weeks of surgery, patients undergo radiation therapy and receive temozolomide PO over 42 days. Beginning 8 days prior to completion of chemoradiotherapy, patients receive plerixafor IV continuously for 2-4 weeks. Patients also receive temozolomide PO 5 days a month beginning 35 days after completion of radiation therapy.
Treatment (radiation therapy, temozolomide, plerixafor)	laboratory biomarker analysis	Within 4 weeks of surgery, patients undergo radiation therapy and receive temozolomide PO over 42 days. Beginning 8 days prior to completion of chemoradiotherapy, patients receive plerixafor IV continuously for 2-4 weeks. Patients also receive temozolomide PO 5 days a month beginning 35 days after completion of radiation therapy.
Treatment (radiation therapy, temozolomide, plerixafor)	pharmacological study	Within 4 weeks of surgery, patients undergo radiation therapy and receive temozolomide PO over 42 days. Beginning 8 days prior to completion of chemoradiotherapy, patients receive plerixafor IV continuously for 2-4 weeks. Patients also receive temozolomide PO 5 days a month beginning 35 days after completion of radiation therapy.
Treatment (radiation therapy, temozolomide, plerixafor)	plerixafor	Within 4 weeks of surgery, patients undergo radiation therapy and receive temozolomide PO over 42 days. Beginning 8 days prior to completion of chemoradiotherapy, patients receive plerixafor IV continuously for 2-4 weeks. Patients also receive temozolomide PO 5 days a month beginning 35 days after completion of radiation therapy.

Primary Outcome Measures

Name	Time	Method
Dose-limiting Toxicity	Up to 30 days post plerixafor	Dose Limiting Toxicity is defined as defined as any hematologic or on-hematologic adverse events grade 3 or higher using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 with a suspected causal relationship to Plerixafor (including electrocardiogram changes indicative of ischemia, ventricular tachycardia)
Participants Alive and Without Disease Progression At 6 Months After the Start of the Irradiation	6 months from start of irradiation	Progression free survival based on the Response Assessment for Neuro-Oncology (RANO) criteria, using both clinical examinations and MRIs with and without contrast summarized with Kaplan Meier estimates.

Trial Locations

Locations (1)

Stanford University, School of Medicine; 🇺🇸 Stanford, California, United States