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)
Conditions
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.
Interventions
RADIATIONradiation therapy
Undergo radiation therapy
DRUGtemozolomide
Given PO
DRUGplerixafor
Given IV
OTHERlaboratory biomarker analysis
Correlative studies
OTHERpharmacological study
Correlative studies
Sponsors
National Cancer Institute (NCI)
Lawrence Recht
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
A total of 30 patients were enrolled at one study center.
Pre-assignment details
A total of 32 subjects were screened. One was a screen failure, one withdrew consent prior to initiating the infusion. Twenty-nine subjects enrolled and completed the 28 day Plerixafor infusion. One subject enrolled but did not complete the infusion due to an unrelated adverse event.
Participants by arm
| Arm | Count |
|---|---|
| Escalation: Plerixafor 200 mcg/kg/Day One week prior to the completion of radiotherapy with concurrent temozolomide, patients with newly diagnosed glioblastoma will receive continuous infusion of Plerixafor at a dose of 200 mcg/kg/day over 4 weeks. | 3 |
| Escalation: Plerixafor 400 mcg/kg/Day One week prior to the completion of radiotherapy with concurrent temozolomide, patients with newly diagnosed glioblastoma will receive continuous infusion of Plerixafor at a dose of 400 mcg/kg/day over 4 weeks. | 6 |
| Expansion: Plerixafor 400 mcg/kg/Day One week prior to the completion of radiotherapy with concurrent temozolomide, patients with newly diagnosed glioblastoma will receive continuous infusion of Plerixafor at a dose of 400 mcg/kg/day over 4 weeks. | 20 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Unrelated Adverse Event | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Escalation: Plerixafor 200 mcg/kg/Day | Escalation: Plerixafor 400 mcg/kg/Day | Expansion: Plerixafor 400 mcg/kg/Day | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 3 Participants | 5 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 3 Participants | 15 Participants | 20 Participants |
| Age, Continuous | 64 years | 62 years | 60 years | 60 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 6 Participants | 19 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 5 Participants | 14 Participants | 22 Participants |
| Region of Enrollment United States | 3 participants | 6 participants | 20 participants | 29 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 1 Participants | 4 Participants | 15 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 6 | 1 / 21 |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 21 / 21 |
| serious Total, serious adverse events | 1 / 3 | 0 / 6 | 3 / 21 |
Outcome results
Primary
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)
Time frame: Up to 30 days post plerixafor
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Escalation: Plerixafor 200 mcg/kg/Day | Dose-limiting Toxicity | 0 Participants |
| Escalation: Plerixafor 400 mcg/kg/Day | Dose-limiting Toxicity | 0 Participants |
| Expansion: Plerixafor 400 mcg/kg/Day | Dose-limiting Toxicity | 0 Participants |
Primary
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.
Time frame: 6 months from start of irradiation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Escalation: Plerixafor 200 mcg/kg/Day | Participants Alive and Without Disease Progression At 6 Months After the Start of the Irradiation | 3 Participants |
| Escalation: Plerixafor 400 mcg/kg/Day | Participants Alive and Without Disease Progression At 6 Months After the Start of the Irradiation | 5 Participants |
| Expansion: Plerixafor 400 mcg/kg/Day | Participants Alive and Without Disease Progression At 6 Months After the Start of the Irradiation | 19 Participants |