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

• ClinicalTrials.gov Identifier: NCT01977677
• Recruitment Status: Completed
• First Posted: November 7, 2013
• Results First Posted: July 3, 2018
• Last Update Posted: October 23, 2018
• Sponsor: Lawrence Recht
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Lawrence Recht, Stanford University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Adult Ependymoblastoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Oligodendroglial Tumors; Adult Pineoblastoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET)	Radiation: radiation therapy; Drug: temozolomide; Drug: plerixafor; Other: laboratory biomarker analysis; Other: pharmacological study	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: November 2014
• Actual Primary Completion Date: November 2017
• Actual Study Completion Date: September 2018

Arms and Interventions

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.

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

Outcome Measures

Primary Outcome Measures :

1. Dose-limiting Toxicity [ Time Frame: 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)
2. Participants Alive and Without Disease Progression At 6 Months After the Start of the Irradiation [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Stanford University, School of Medicine

Stanford, California, United States, 94305

Sponsors and Collaborators

Lawrence Recht

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Lawrence Recht; Stanford University Hospitals and Clinics

  Study Documents (Full-Text)

Documents provided by Lawrence Recht, Stanford University:

Study Protocol and Statistical Analysis Plan  [PDF] April 29, 2015

More Information

• Responsible Party: Lawrence Recht, Professor of Neurology, Stanford University
• ClinicalTrials.gov Identifier: NCT01977677
• Other Study ID Numbers: BRN0023; NCI-2013-02012 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); BRN0023 ( Other Identifier: Stanford University Hospitals and Clinics ); P30CA124435 ( U.S. NIH Grant/Contract )
• First Posted: November 7, 2013
• Results First Posted: July 3, 2018
• Last Update Posted: October 23, 2018
• Last Verified: September 2018

Additional relevant MeSH terms:

Glioblastoma; Glioma; Gliosarcoma; Medulloblastoma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Pinealoma; Sarcoma, Ewing; Neuroectodermal Tumors, Primitive, Peripheral; Neoplasms; Astrocytoma; Neoplasms, Neuroepithelial; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Plerixafor; Temozolomide