Whole Brain Radiation Therapy With Standard Temozolomide Chemo-Radiotherapy and Plerixafor in Treating Patients With Glioblastoma

• ClinicalTrials.gov Identifier: NCT03746080
• Recruitment Status: Recruiting
• First Posted: November 19, 2018
• Last Update Posted: July 11, 2022
• Sponsor: Lawrence D Recht
• Collaborator: Sanofi
• Information provided by (Responsible Party): Lawrence D Recht, Stanford University

Tracking Information

• First Submitted Date: November 7, 2018
• First Posted Date: November 19, 2018
• Last Update Posted Date: July 11, 2022
• Actual Study Start Date: December 4, 2018
• Estimated Primary Completion Date: January 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 24, 2020)

Progression-free survival (PFS) at six months [ Time Frame: 6 months ]

Progression free survival will be measured at 6 months post initiation of chemoradiation. Simon 2-stage design will be use to assess progression-free survival. Will be computed from start of induction therapy and summarized with Kaplan-Meier estimates.

Original Primary Outcome Measures (submitted: November 14, 2018)

Progression-free survival (PFS) at six months [ Time Frame: 6 months ]

Progression free survival will be measured at 6 months from diagnosis by biopsy or surgical resection. Simon 2-stage design will be use to assess progression-free survival. Will be computed from start of induction therapy and summarized with Kaplan-Meier estimates.

Current Secondary Outcome Measures (submitted: December 5, 2018)

• Median Survival [ Time Frame: 32 months ]
  Median survival will be assessed at 32 months of subjects who have completed the 28 day Plerixafor infusion. Will be computed from start of induction therapy and summarized with Kaplan-Meier estimates.
• Toxicity associated with Plerixafor/WBRT [ Time Frame: 30 days ]
  Incidence of adverse events will be graded and recorded per Common Terminology Criteria for Adverse Events version 5.0. Will assess reported toxicities up until 30 days of treatment. Adverse events and qualifying dose limiting toxicities (DLTs) will be tabulated by cohort, site and severity.
• Patterns of treatment failure [ Time Frame: 5 years ]
  Will assess pattern of failure (out-of-field occurrence or occurrence outside of the brain) over time. Local treatment failure is defined as within the 95% isodose region

Original Secondary Outcome Measures (submitted: November 14, 2018)

• Median Survival [ Time Frame: 32 months ]
  Median survival will be assessed at 32 months of subjects who have completed the 28 day Plerixafor infusion. Will be computed from start of induction therapy and summarized with Kaplan-Meier estimates.
• Toxicity associated with Plerixafor/WBRT [ Time Frame: 30 days ]
  Incidence of adverse events will be graded and recorded per Common Terminology Criteria for Adverse Events version 5.0. Will assess reported toxicities up until 30 days of treatment. Adverse events and qualifying dose limiting toxicities (DLTs) will be tabulated by cohort, site and severity.
• Patterns of treatment failure [ Time Frame: 5 years ]
  Will assess pattern of failure (out-of-field occurrence or occurrence outside of the brain) over time. Local treatment failure is defined as within the 95% isodose region
• Neurocognitive outcome [ Time Frame: 5 years ]
  Neurocognitive outcome measure will be assessed in 6, 12 and 24 months and yearly after for 3 years after the start of radiation. It will be measured using NRG-CC001 neurocognitive assessment tool. Changes in neurocognitive outcomes will be analyzed with a linear mixed-effect model, with a random effect for patient, to account for correlation over time within patient.
• Quality of Life by European Organisation for Research and Treatment of Cancer (EORTC-QLQ C30) Survey [ Time Frame: 5 years ]
  European Organisation for Research and Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ C30) quality of life surveys will be administered at 6 and 12 and 24 months and yearly after for 3 years after the start of radiation to assess health-related quality of life (HR-QOL). The outcome is expressed as the mean with 95% confidence interval
• Quality of life by Brain-20 (BN-20) survey [ Time Frame: 5 years ]
  Brain-20 (BN-20) quality of life surveys will be administered at 6 and 12 and 24 months and yearly after for 3 years after the start of radiation to assess health-related quality of life (HR-QOL). The outcome is expressed as the mean with 95% confidence interval
• Quality of life by EuroQol-5D (EQ-5D) survey [ Time Frame: 5 years ]
  EuroQol-5D (EQ-5D) quality of life surveys will be administered at 6 and 12 and 24 months and yearly after for 3 years after the start of radiation to assess health-related quality of life (HR-QOL). The outcome is expressed as the mean with 95% confidence interval

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Whole Brain Radiation Therapy With Standard Temozolomide Chemo-Radiotherapy and Plerixafor in Treating Patients With Glioblastoma
• Official Title: A Follow-Up Study to Add Whole Brain Radiotherapy (WBRT) to Standard Temozolomide Chemo-Radiotherapy in Newly Diagnosed Glioblastoma (GBM) Treated With 4 Weeks of Continuous Infusion Plerixafor
• Brief Summary: This phase II trial studies how well whole brain radiation therapy works with standard temozolomide chemo-radiotherapy and plerixafor in treating patients with glioblastoma (brain tumor). Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Plerixafor is a drug that may prevent recurrence of glioblastoma after radiation treatment. Giving whole brain radiation therapy with standard temozolomide chemo-radiotherapy and plerixafor may work better in treating patients with glioblastoma.

Detailed Description

PRIMARY OBJECTIVES:

I. The primary purpose of this Phase II study is to evaluate the efficacy of Plerixafor administered with a modified radiation regimen that includes a component of WBRT. The primary endpoint is 6-month progression free survival post initiation of Chemoradiation.

SECONDARY OBJECTIVES:

I. To assess the median survival of patients treated with continuous infusion plerixafor/WBRT.

II. To assess the toxicities both short and long term of continuous infusion plerixafor/WBRT.

III. To assess the patterns of failure (in and out of irradiated brain field, out of brain) of continuous infusion plerixafor/WBRT.

OUTLINE:

After completion maximal safe surgical resection, patients undergo radiation therapy for 42 days, initiating whole brain radiation therapy at day 21 (dose 16 of radiation therapy) and receive temozolomide daily on days 1-42. Beginning 7 days before the completion of whole brain radiation therapy, patients receive plerixafor by continuous infusion on days 1-28. Beginning 1 week after completion of plerixafor infusion and 35 days after completion of whole brain radiation therapy, patients receive temozolomide monthly for 6-12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for adverse events for 30 days after the last dose of Plerixafor and then every 12 weeks for 5 years for survival follow-up.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Glioblastoma
• Glioblastoma With Primitive Neuronal Component
• Gliosarcoma
• Malignant Glioma
• Oligodendroglial Component Present

Intervention

• Drug: Plerixafor
  Plerixafor will be administered via infusion at 400 micrograms per kilogram per day for four weeks beginning one week before the end of radiation
  Other Names:

  • AMD 3100
  • JM-3100
  • Mozobil
  • SDZ SID 791
• Drug: Temozolomide
  Temozolomide (TMZ) will be administered concurrently with the radiation for 42 days and 6-12 cycles of monthly adjuvant Temozolomide (TMZ) after completion of Plerixafor infusion.
  Other Names:

  • CCRG-81045
  • Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-
  • M & B 39831
  • M and B 39831
  • Methazolastone
  • RP-46161
  • SCH 52365
  • Temcad
  • Temodal
  • Temodar
  • Temomedac
• Radiation: Whole-Brain Radiotherapy (WBRT)
  Undergo Whole brain radiotherapy (WBRT) - Radiotherapy consists of 30 Gy in 15 fractions of whole brain radiations
  Other Names:

  • WBRT
  • whole-brain radiation therapy
  • whole-brain radiotherapy
• Radiation: Radiation Therapy
  Radiotherapy consists of 30 Gy in 15 fractions
  Other Names:

  • XRT
  • RT

Study Arms

Experimental: Whole Brain Radiotherapy + Plerixafor +Chemoradiotherapy

After completion maximal safe surgical resection, patients undergo radiation therapy for 42 days, initiating whole brain radiation therapy at day 21 (dose 16 of radiation therapy) and receive temozolomide daily on days 1 to 42. Beginning 7 days before the completion of whole brain radiation therapy, patients receive plerixafor by continuous infusion on days to 1 to 28. Beginning 1 week after completion of plerixafor infusion and 35 days after completion of whole brain radiation therapy, patients receive temozolomide monthly for 6 to 12 courses in the absence of disease progression or unacceptable toxicity.

Interventions:

• Drug: Plerixafor
• Drug: Temozolomide
• Radiation: Whole-Brain Radiotherapy (WBRT)
• Radiation: Radiation Therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 14, 2018): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2027
• Estimated Primary Completion Date: January 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients must have tissue confirmation of high grade (World Health Organization (WHO) grade IV) glioma including but not limited to glioblastoma, gliosarcoma, glioblastoma with oligodendroglial features, glioblastoma with primitive neuroectodermal tumor (PNET) features.
• The patient must have post-operative contrast enhanced imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) unless only biopsy performed. For patients having biopsy alone, post-operative imaging is not routinely obtained and therefore 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 chemo-radiation as specified in the protocol.
• Patients must have Karnofsky performance score >= 60.
• Absolute neutrophil count (ANC) >= 1500 (at time of screening).
• Platelets >= 100,000 ml (at time of screening).
• Serum creatinine =< 1.5mg/dl (at time of screening).
• Creatinine (Cr) clearance should be > 50 mL/min (at time of screening).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 times the upper limit of normal (at time of screening).
• If female of childbearing potential, negative pregnancy test (at time of screening).
• 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.
• Prior malignancy except for non-melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 3 years prior to 1st dose of investigational drug.
• Prior sensitivity to plerixafor.
• Pregnant or patients who are breastfeeding.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Hari Priya Yerraballa; 6507249363; yhpriya@stanford.edu

Contact: Sophie Bertrand; 650-723-4467; sophieb@stanford.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03746080
• Other Study ID Numbers: IRB-46410; NCI-2018-02159 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); BRN0037 ( Other Identifier: OnCore Number ); IRB-46410 ( Other Identifier: Stanford IRB )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Lawrence D Recht, Stanford University
• Original Responsible Party: Stanford University
• Current Study Sponsor: Lawrence D Recht
• Original Study Sponsor: Stanford University
• Collaborators: Sanofi

Investigators

• Principal Investigator: Lawrence Recht; Stanford Cancer Institute Palo Alto

• PRS Account: Stanford University
• Verification Date: July 2022