Clinical trial NCT01977677: Plerixafor After Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed High Grade Glioma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: 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)
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-11-07
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Dose-limiting Toxicity
timeFrame: Up to 30 days post plerixafor
measure: Participants Alive and Without Disease Progression At 6 Months After the Start of the Irradiation
timeFrame: 6 months from start of irradiation
Secondary outcomes:
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University, School of Medicine
state: California
Study officials:
affiliation: Stanford University Hospitals and Clinics
name: Lawrence Recht
role: PRINCIPAL_INVESTIGATOR
References: