CompletedNCT01977677Updated Oct 23, 2018Results posted

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

A Phase 1/2 interventional study of radiation therapy and temozolomide in Adult Ependymoblastoma, Adult Giant Cell Glioblastoma and Adult Glioblastoma, sponsored by Lawrence Recht. Completed at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2018-10-23.

Sponsored by Lawrence Recht · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 30
Allocation: Not applicable
Ages: 18 Years to 75 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

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)

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Who can participate

Ages eligible: 18 Years to 75 Years
Sexes eligible: All
Accepts 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

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

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 30 participants (actual)

Study arms

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 · Drug: temozolomide · Drug: plerixafor · Other: laboratory biomarker analysis · Other: pharmacological study

Interventions

Radiationradiation therapy
Undergo radiation therapy
Also known as: irradiation, radiotherapy, therapy, radiation
Drugtemozolomide
Given PO
Also known as: SCH 52365, Temodal, Temodar, TMZ
Drugplerixafor
Given IV
Also known as: AMD 3100, Mozobil
Otherlaboratory biomarker analysis
Correlative studies
Otherpharmacological study
Correlative studies
Also known as: pharmacological studies

What researchers measure

Primary outcomes

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
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

Results

Posted Jul 3, 2018

Participant flow

A total of 30 patients were enrolled at one study center.

Participant flow — Overall Study
Milestone	Escalation: Plerixafor 200 mcg/kg/Day	Escalation: Plerixafor 400 mcg/kg/Day	Expansion: Plerixafor 400 mcg/kg/Day
Started	3	6	21
Completed	3	6	20
Not completed	0	0	1
Withdrew: Unrelated adverse event	0	0	1

Outcome measures

PrimaryDose-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
Reported as:: Count of participants · Participants

Dose-limiting Toxicity
Participants	Escalation: Plerixafor 200 mcg/kg/Day	Escalation: Plerixafor 400 mcg/kg/Day	Expansion: Plerixafor 400 mcg/kg/Day
Dose-limiting Toxicity	0	0	0

PrimaryParticipants 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
Reported as:: Count of participants · Participants

Participants Alive and Without Disease Progression At 6 Months After the Start of the Irradiation
Participants	Escalation: Plerixafor 200 mcg/kg/Day	Escalation: Plerixafor 400 mcg/kg/Day	Expansion: Plerixafor 400 mcg/kg/Day
Participants Alive and Without Disease Progression At 6 Months After the Start of the Irradiation	3	5	19

Adverse events

Collected over Up to 30 days after Plerixafor Infusion. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Escalation: Plerixafor 200 mcg/kg/Day	0/3 (0%)	1/3 (33.3%)	3/3 (100%)
Escalation: Plerixafor 400 mcg/kg/Day	0/6 (0%)	0/6 (0%)	6/6 (100%)
Expansion: Plerixafor 400 mcg/kg/Day	1/21 (4.8%)	3/21 (14.3%)	21/21 (100%)

Most frequent serious events

Most frequent serious events
Event	Escalation: Plerixafor 200 mcg/kg/Day	Escalation: Plerixafor 400 mcg/kg/Day	Expansion: Plerixafor 400 mcg/kg/Day
PseudoprogressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)	1/3	0/6	0/21
Abdominal PainGastrointestinal disorders	0/3	0/6	1/21
Disease ProgressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/3	0/6	1/21
EncephalopathyNervous system disorders	0/3	0/6	1/21
Hemorrhagic hepatic cystNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/3	0/6	1/21

Most frequent other events

Showing 10 of 58

Most frequent other events
Event	Escalation: Plerixafor 200 mcg/kg/Day	Escalation: Plerixafor 400 mcg/kg/Day	Expansion: Plerixafor 400 mcg/kg/Day
DiarrheaGastrointestinal disorders	2/3	2/6	3/21
InsomniaPsychiatric disorders	1/3	4/6	7/21
NauseaGastrointestinal disorders	0/3	3/6	3/21
ConjunctivitisEye disorders	1/3	3/6	0/21
DyspepsiaGastrointestinal disorders	1/3	1/6	1/21
HeadacheNervous system disorders	1/3	2/6	4/21
ParasthesiaNervous system disorders	1/3	1/6	0/21
FatigueGeneral disorders	1/3	1/6	6/21
Hot FlashesVascular disorders	1/3	2/6	5/21
HypertensionVascular disorders	1/3	0/6	0/21

Baseline characteristics

Only subjects who completed the 4 week infusion were included

Age, Categorical
Age, Categorical(Participants)	Escalation: Plerixafor 200 mcg/kg/Day	Escalation: Plerixafor 400 mcg/kg/Day	Expansion: Plerixafor 400 mcg/kg/Day	Total
<=18 years	0	0	0	0
Between 18 and 65 years	2	3	15	20
>=65 years	1	3	5	9

Age, Continuous
Age, Continuous(years)	Escalation: Plerixafor 200 mcg/kg/Day	Escalation: Plerixafor 400 mcg/kg/Day	Expansion: Plerixafor 400 mcg/kg/Day	Total
Median	64 (55 to 67)	62 (40 to 74)	60 (29 to 74)	60 (29 to 74)

Sex: Female, Male
Sex: Female, Male(Participants)	Escalation: Plerixafor 200 mcg/kg/Day	Escalation: Plerixafor 400 mcg/kg/Day	Expansion: Plerixafor 400 mcg/kg/Day	Total
Female	2	2	5	9
Male	1	4	15	20

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Escalation: Plerixafor 200 mcg/kg/Day	Escalation: Plerixafor 400 mcg/kg/Day	Expansion: Plerixafor 400 mcg/kg/Day	Total
Hispanic or Latino	0	0	1	1
Not Hispanic or Latino	3	6	19	28
Unknown or Not Reported	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Escalation: Plerixafor 200 mcg/kg/Day	Escalation: Plerixafor 400 mcg/kg/Day	Expansion: Plerixafor 400 mcg/kg/Day	Total
American Indian or Alaska Native	0	0	0	0
Asian	0	1	4	5
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	0	0	2	2
White	3	5	14	22
More than one race	0	0	0	0
Unknown or Not Reported	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Escalation: Plerixafor 200 mcg/kg/Day	Escalation: Plerixafor 400 mcg/kg/Day	Expansion: Plerixafor 400 mcg/kg/Day	Total
United States	3	6	20	29

Study locations

1 site

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

References and documents

Study documents

Protocol and statistical analysis plan · Apr 29, 2015

Documents are hosted by the registry — open the source record to download them.

Registry details

Key details

Study ID: NCT01977677
Lead sponsor: Lawrence Recht
Collaborators: National Cancer Institute (NCI)
Responsible party: Lawrence Recht (Professor of Neurology, Stanford University) — Sponsor-investigator
First posted: Nov 7, 2013
Start date: Nov 2014
Primary completion: Nov 2017
Completion: Sep 2018
Results posted: Jul 3, 2018
Last update: Oct 23, 2018

Study contacts

Lawrence Recht

principal investigator · Stanford University Hospitals and Clinics

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Sep 2018. You cannot join it, but the record below documents what was studied.

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