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

• Register: ClinicalTrials.gov
• Last refreshed on: 26 April 2021
• Main ID: NCT02903069
• Date of registration: 07/09/2016
• Prospective Registration: No
• Primary sponsor: Celgene
• Public title: Study of Marizomib With Temozolomide and Radiotherapy in Patients With Newly Diagnosed Brain Cancer
• Scientific title: Phase 1b, Multicenter, Open-Label Study of Marizomib With Temozolomide and Radiotherapy in Patients With Newly Diagnosed WHO Grade IV Malignant Glioma
• Date of first enrolment: August 17, 2016
• Target sample size: 66
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02903069
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Canada, Switzerland, United States

Contacts

• Name: Ileana Elias, M.D.
• Affiliation: Celgene Corporation

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

- Willing and able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

- Co-medication or concomitant therapy that may interfere with study results

- History of thrombotic or hemorrhagic stroke or myocardial infarction within 6 months

- Other chemotherapy or anti-tumor treatment for brain tumor (other than therapies
required by the inclusion criteria of this protocol)

- 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Malignant Glioma

Glioblastoma

Intervention(s)

Drug: TMZ

Drug: MRZ

Radiation: RT

Device: Optune

Primary Outcome(s)

Determine MRZ maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for both concomitant treatment (MRZ + TMZ + RT) and adjuvant treatment (MRZ + TMZ) [Time Frame: 42-day concomitant treatment and 28-day Cycle 1 adjuvant treatment]

To assess adverse events during the adjuvant treatment [Time Frame: From the first dose of study drug through 28 days after the last dose]

Secondary Outcome(s)

Evaluate the activity (overall survival [OS]) of MRZ + TMZ + RT [Time Frame: Survival monitored throughout the concomitant and adjuvant treatment periods and every three months during long-term follow-up for 2 years]

MRZ pharmacokinetics - Elimination Half-Life (t1/2) [Time Frame: Day1 and Day 8 during Stage 1 (dose-escalation)]

MRZ pharmacokinetics - Volume of Distribution (Vd) [Time Frame: Day1 and Day 8 during Stage 1 (dose-escalation)]

Evaluate the activity (progression-free survival [PFS]) of MRZ + TMZ + Optune [Time Frame: MRI assessments at Week 10 during concomitant treatment and every even Cycle during adjuvant treatment, death monitored throughout the treatment periods, and disease progression and death monitored every 3 months during long-term follow-up for 2 years]

TMZ serum concentration [Time Frame: On Day 1 of Week 1 (D1) and on Day 1 of Week 2 (D8), TMZ serum concentration will be measured before treatment, and 60 minutes after the dose and 24 hrs after the dose (prior to the Day 9 TMZ dose)]

Evaluate the activity (overall survival [OS]) of MRZ + TMZ + Optune [Time Frame: Survival monitored throughout the concomitant and adjuvant treatment periods and every three months during long-term follow-up for 2 years]

Assess adverse events during concomitant and adjuvant treatment [Time Frame: From the first dose of study drug through 28 days after the last dose]

MRZ pharmacokinetics - Clearance (CL) [Time Frame: Day1 and Day 8 during Stage 1 (dose-escalation)]

Assess neurological coordination using the Scale for the Assessment and Rating for Ataxia (SARA) [Time Frame: Assessments made at baseline and then weeks 1, 5, and 8 during concomitant treatment, on Day 1 of each Cycle during adjuvant treatment, and at the end of treatment visit (28 days after last dose of study drug)]

MRZ pharmacokinetics - Area Under the Blood Concentration-Time Curve (AUC0-t, AUC0-inf) [Time Frame: Day1 and Day 8 during Stage 1 (dose-escalation)]

Evaluate the activity (progression-free survival [PFS]) of MRZ + TMZ + RT [Time Frame: 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) [Time Frame: Day 1 and Day 8 during Stage 1 (dose-escalation)]

To confirm the MRZ RP2D for concomitant and adjuvant treatment in an expanded group of patients [Time Frame: 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]

Secondary ID(s)

MRZ-112

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Triphase