Study of Marizomib With Temozolomide and Radiotherapy in Patients With Newly Diagnosed Brain Cancer

NCT02903069 | Completed Phase 1

• 1 other identifier: MRZ-112
• Study Type: interventional
• Target: 66
• Locations: 3 countries
• Sites: 8

Brief Summary

This study is for newly diagnosed WHO Grade IV malignant glioma patients to determine whether an investigational drug known as marizomib (MRZ) will improve the treatment of newly diagnosed glioblastoma patients by delaying the growth of the cancer, reducing the size of the tumor, and/or improving survival. Marizomib (MRZ) is being added to standard-of-care treatments of radiotherapy (RT), temozolomide (TMZ), and Optune.

Conditions

Glioblastoma; Malignant Glioma

Keywords

newly diagnosed; malignant glioma; WHO Grade 4; WHO Grade IV; marizomib; MRZ; TMZ; RT; brain cancer; proteasome inhibitor; radiation; temozolomide; temodar; chemotherapy; concurrent; adjuvant; Optune; Novocure; NovoTTF

Outcome Measures

Primary Outcomes (2)

• Determine MRZ maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for both concomitant treatment (MRZ + TMZ + RT) and adjuvant treatment (MRZ + TMZ)

  Assess dose-limiting toxicities (DLTs) in each dose-escalation arm

  42-day concomitant treatment and 28-day Cycle 1 adjuvant treatment

• To assess adverse events during the adjuvant treatment

  To assess the safety of the combination of MRZ and TMZ with the addition of Optune™ in patients entering Adjuvant Treatment

  From the first dose of study drug through 28 days after the last dose

Secondary Outcomes (13)

• To confirm the MRZ RP2D for concomitant and adjuvant treatment in an expanded group of patients

  Assessments made during the concomitant (dosing for 42 days of a 10-week treatment period) and adjuvant (one or more 28-day cycles) treatment periods in the dose-expansion stage of the study

• Assess adverse events during concomitant and adjuvant treatment

  From the first dose of study drug through 28 days after the last dose

• Evaluate the activity (overall survival [OS]) of MRZ + TMZ + RT

  Survival monitored throughout the concomitant and adjuvant treatment periods and every three months during long-term follow-up for 2 years

• Evaluate the activity (progression-free survival [PFS]) of MRZ + TMZ + RT

  MRI assessments at Week 10 during concomitant trt and every even Cycle during adjuvant treatment, death monitored throughout the treatment periods, and disease progression and death monitored every three months during long-term follow-up for 2 years

• MRZ pharmacokinetics - Maximum Serum Concentration (Cmax)

  Day 1 and Day 8 during Stage 1 (dose-escalation)

Study Arms (4)

Stage 1: Concomitant Treatment

EXPERIMENTAL

MRZ + TMZ + RT Patients who complete Concomitant Treatment may continue on to Adjuvant Treatment.

Drug: MRZ; Drug: TMZ; Radiation: RT

Stage 1: Adjuvant Treatment

EXPERIMENTAL

MRZ + TMZ

Drug: MRZ; Drug: TMZ

Stage 2: Dose-Expansion

EXPERIMENTAL

MRZ + TMZ + RT followed by MRZ + TMZ In Stage 2 (dose-expansion): a minimum of 12 and up to approximately 18 additional evaluable patients will be enrolled in a cohort in which Concomitant Treatment (MRZ + TMZ + RT) is followed by Adjuvant Treatment (MRZ + TMZ) to confirm the MTD for each treatment regimen as determined in the Dose-Escalation (Stage 1), and to assess preliminary activity of the recommended Phase 2 dose (RP2D).

Drug: MRZ; Drug: TMZ; Radiation: RT

Optune Arm

EXPERIMENTAL

MRZ + TMZ + Optune

Drug: MRZ; Drug: TMZ; Device: Optune

Interventions

MRZ DRUG

MRZ dose ranges from 0.55 to 1.2 mg/m2 given IV over 10 minutes on Days 1, 8, 15, 29, and 36 during Concomitant Treatment. MRZ dose ranges from 0.55 to 1.2 mg/m2 given IV over 10 minutes on Days 1, 8, 15 every 28 days during Adjuvant Treatment. IV hydration will be given prior to the MRZ infusion.

Also known as: NPI-0052

Optune Arm; Stage 1: Adjuvant Treatment; Stage 1: Concomitant Treatment; Stage 2: Dose-Expansion

TMZ DRUG

TMZ will be administered once daily, 7 days/week, for 6 weeks, starting on Day 1, at a dose of 75 mg/m2 during Concomitant Treatment. TMZ will be administered once daily on Days 1-5 every cycle, dose range 150 to 200 mg/m2 during Adjuvant Treatment.

Also known as: temozolomide, Temodar

Optune Arm; Stage 1: Adjuvant Treatment; Stage 1: Concomitant Treatment; Stage 2: Dose-Expansion

RT RADIATION

Focal RT will be administered once daily, 5 days/week, for 30 doses over 6 weeks to a total dose of 60 Gy, starting on Day 1 during Concomitant Treatment.

Also known as: radiation therapy

Stage 1: Concomitant Treatment; Stage 2: Dose-Expansion

Optune DEVICE

Tumor Treating Fields Therapy device to be worn ≥ 18 hours per day.

Also known as: NovoTTF-100A

Optune Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form
• Males and females of age ≥ 18 years or of age ≥ 22 years for those assigned to Optune™ at the time of signing of the informed consent document.
• Histologically confirmed newly diagnosed G4 MG
• Karnofsky Performance Status (KPS) score ≥ 70%
• For Concomitant Treatment: Prior tumor resection or biopsy up to 8 weeks prior to first MRZ dose
• For Adjuvant Treatment: All AEs resulting from surgery must have resolved to NCI-CTCAE (v. 4.03) Grade ≤ 1
• Stable or decreasing dose of corticosteroids over 14 days prior to first MRZ dose
• For Concomitant Treatment: No prior treatment with MRZ or any other PIs, including BTZ, carfilzomib (CFZ), or ixazomib (IXZ)
• For Adjuvant Treatment: No prior treatment with BTZ, CFZ, or IXZ
• No investigational agent within 4 weeks prior to first dose of study drug
• Adequate hematological, renal, and hepatic function
• Patients must be without seizures for at least 14 days prior to enrollment, and patients who receive treatment with AEDs must be on stable doses for at least 14 days prior to enrollment
• Absence of known HIV infection, chronic hepatitis B, or hepatitis C infection; absence of any other serious medical condition which could interfere with oral medication intake
• Patients with archival tumor tissue suitable for measurement of proteasome activity and biomarker status must give permission to access and test the tissue. Patients without archival tumor tissue are eligible for the Dose-Escalation stage, but not the Dose-Expansion stage of the study
• For women of child-bearing potential and for men with partners of child-bearing potential, patient must agree to take contraceptive measures for duration of treatments and for one month after last study treatment

You may not qualify if:

• Co-medication or concomitant therapy that may interfere with study results
• History of thrombotic or hemorrhagic stroke or myocardial infarction within 6 months
• Pregnant or breast feeding
• Uncontrolled intercurrent illness that would limit compliance with study requirements, or disorders associated with significant immunocompromised state
• Known other previous/current malignancy requiring treatment within ≤ 3 years except for liited disease treated with curative intent
• Any comorbid condition that confounds the ability to interpret data from the study as judged by the Investigator or Medial Monitor
• For those enrolled in Adjuvant Treatment with Optune™, patients are excluded if they are \< 22 years of age, have an active implanted medical device, a skull defect, bullet fragments in the head, sensitivity to conductive hydrogels, a scalp condition that might interfere with wearing the device, or GBM that is not supratentorial.

Sponsors & Collaborators

• Celgene: lead
• Triphase Research and Development III Corp.: collaborator

Study Sites (8)

University of California San Diego Medical Center

La Jolla, California, 92037, United States

Location

UC Irvine

Orange, California, 92868, United States

Location

John Wayne Cancer Center Outpatient Clinic

Santa Monica, California, 90404, United States

Location

Northwestern Center For Clinical Research

Chicago, Illinois, 60611, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Pennsylvania State University College of Medicine

Hershey, Pennsylvania, 17033, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

University of Zurich Hospital

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Glioblastoma; Glioma; Brain Neoplasms

Interventions

marizomib; Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Ileana Elias, M.D.

  Celgene Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2016
• First Posted: September 16, 2016
• Study Start: August 17, 2016
• Primary Completion: January 25, 2021
• Study Completion: January 25, 2021
• Last Updated: April 19, 2021

Record last verified: 2021-04

Locations

US (6); CA (1); CH (1)