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

A Phase I/II Study of Local Field Irradiation and Temozolomide Followed by Continuous Infusion Plerixafor as an Upfront Therapy for Newly Diagnosed Glioblastoma GBM

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University, School of Medicine

Participation Criteria

Eligibility Criteria

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

Description

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 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: Treatment (radiation therapy, temozolomide, 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.

Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Radiation: radiation therapy; Undergo radiation therapy; Other Names: irradiation; radiotherapy; therapy, radiation; Drug: temozolomide; Given PO; Other Names: Temodar; SCH 52365; Temodal; TMZ; Drug: plerixafor; Given IV; Other Names: Mozobil; AMD 3100

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting Toxicity	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)	Up to 30 days post plerixafor
Participants Alive and Without Disease Progression At 6 Months After the Start of the 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.	6 months from start of irradiation

Collaborators and Investigators

• Sponsor: Lawrence Recht
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Lawrence Recht, Stanford University Hospitals and Clinics

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: October 31, 2013
• First Submitted That Met QC Criteria: November 6, 2013
• First Posted (Estimate): November 7, 2013

Study Record Updates

• Last Update Posted (Actual): October 23, 2018
• Last Update Submitted That Met QC Criteria: September 27, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Glioblastoma; Glioma; Sarcoma, Ewing; Medulloblastoma; Gliosarcoma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Pinealoma; 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: BRN0023 (Other Identifier: Stanford University Hospitals and Clinics); P30CA124435 (U.S. NIH Grant/Contract); NCI-2013-02012 (Registry Identifier: CTRP (Clinical Trial Reporting Program))