Ruxolitinib With Radiation and Temozolomide Compared to Radiation and Temozolomide for Newly Diagnosed Glioblastoma

NCT06991101 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2023-AHL-001
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research is to test the safety and effectiveness of the investigational drug ruxolitinib when it is combined with standard of care treatment (radiation therapy and temozolomide) for the treatment of newly diagnosed glioblastoma. Half the people in the study will be assigned to take the study drug ruxolitinib in addition to the standard of care temozolomide and radiation therapy and the other half will be assigned to the standard of care temozolomide and radiation therapy only. This assignment will be randomized in a 1-to-1 ratio, like the flip of a coin.

Conditions

Glioblastoma; Brain Cancer; Glioblastoma Multiforme; Glioblastoma Multiforme of Brain; Glioblastoma Multiforme, Adult; MGMT-Unmethylated Glioblastoma; MGMT-Methylated Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS) at end of study

  OS is defined as the time from first treatment until the date of death from any cause at the end of the study. Participants who are lost to follow-up will be censored at the time of the last follow-up.

  4 years

Secondary Outcomes (9)

• OS at 12 months

  12 months

• Progression-free survival (PFS) at 6 months

  6 months

• PFS at 12 months

  12 months

• Objective response rate (ORR)

  4 years

• Duration of response (DOR)

  4 years

Study Arms (2)

Ruxolitinib plus Radiation and Temozolomide

EXPERIMENTAL

There will be two phases of drug administration: (1) Ruxolitinib and temozolomide will be administered "During Radiation Therapy" and (2) Maintenance phase after radiation therapy is complete.

Drug: Ruxolitinib; Drug: Temozolomide; Radiation: Radiation Therapy

Radiation and Temozolomide

ACTIVE COMPARATOR

There will be two phases of drug administration: (1) Temozolomide will be administered "During Radiation Therapy" and (2) Maintenance phase after radiation therapy is complete.

Drug: Temozolomide; Radiation: Radiation Therapy

Interventions

Ruxolitinib DRUG

"During Radiation Therapy" phase: 20 mg ruxolitinib will be self-administered orally (PO) twice every day (BID), starting on Day 1 for 6 weeks. Then there will be a 4-week break after radiotherapy is complete. "Maintenance" phase: Occurs thirty days (4 weeks) after receiving the last dose of radiotherapy. Ruxolitinib 20 mg will be self-administered PO BID, starting on Day 1 in consecutive 28-day cycles. Either phase: Aside from the 30-day break, ruxolitinib will be continued daily until disease progression or treatment intolerance. Ruxolitinib should be administered at approximately the same time each day. The tablets should be swallowed whole with water and should not be opened, broken, or chewed. The dose may be reduced in the case of certain adverse events.

Also known as: Jakavi

Ruxolitinib plus Radiation and Temozolomide

Temozolomide DRUG

"During Radiation Therapy" phase: 75 mg/m\^2 will be self-administered PO once every day, starting on Day 1, for 6 weeks. Then there will be a 4-week break after radiotherapy is complete. "Maintenance" phase: Occurs thirty days (4 weeks) after receiving the last dose of radiotherapy. Temozolomide 150-200 mg/m\^2 will be self-administered PO BID, starting on Day 1 to Day 5 of each cycle for six cycles. Either phase: The dose may be reduced in the case of certain adverse events.

Also known as: Temodar

Radiation and Temozolomide; Ruxolitinib plus Radiation and Temozolomide

Radiation Therapy RADIATION

Radiation will be administered every weekday (Monday to Friday) in 2 Gy fractions for 30 fractions during a 6-week period (60 Gy total).

Radiation and Temozolomide; Ruxolitinib plus Radiation and Temozolomide

Eligibility Criteria

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

You may qualify if:

• Provision of signed informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Individuals of any sex, gender, race, or ethnicity ≥ 18 years of age.
• Histologically confirmed glioblastoma as defined by the World Health Organization (WHO) 2021 Criteria (IDH-wildtype) that is either methylated, unmethylated, or indeterminate MGMT.
• Confirmation that patient has sufficient tissue to undergo MGMT and IDH testing, as mandated.
• Must have a Karnofsky performance status (KPS) ≥ 70% (i.e., the patient must be able to care for themself with occasional help from others).
• Adequate organ (liver and renal) and bone marrow function within 14 days before randomization. For all parameters listed below, the most recent results available must be used:
• Absolute neutrophil count (ANC) ≥ 1500/mm3. Note: Granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 1 week prior to screening assessment.
• Platelet count ≥ 100,000/mm3. Note: Platelet transfusion is not allowed within 1 week prior to registration.
• Total bilirubin (TBL) ≤ 1.5 × institutional upper limit of normal (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN.
• Serum albumin ≥ 2.5 g/dL.
• Patients able to become pregnant: use of highly effective contraception for at least one (1) month prior to screening and agreement to use such a method. Should a participant become pregnant or suspect that they are pregnant while participating in this study, they should notify the treating physician immediately. Such individuals must have a negative pregnancy test.
• Patients must have no concurrent malignancy except curatively treated early-stage bladder and prostate cancer that has been completed resected, basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast, adequately treated stage I or II cancer from which the patient is in complete remission. Patients with other prior malignancies must be disease-free for ≥ 3 years.

You may not qualify if:

• Patients who are pregnant or breast-feeding. The anti-proliferative activity of this experimental drug and temozolomide may be harmful to the developing fetus or nursing infant.
• Patients receiving concurrent therapy for their brain tumor (e.g., chemotherapeutics or investigational agents).
• Patients with a concurrent or prior malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin. Patients who have been free of disease (any prior malignancy) for at least 3 years are eligible for this study.
• Patients who have had repeat craniotomy for tumor therapy after receiving radiation therapy and temozolomide treatment.
• Patients who received other chemotherapeutics or investigational agents in addition to their radiation therapy and concomitant temozolomide treatment.
• Patient has previously taken ruxolitinib or is allergic to components of the study drug.
• Patients using warfarin.
• Uncontrolled immunodeficiency virus infection or active tuberculosis.
• Patients with active serious infections requiring systemic therapy.
• Known Active hepatitis B virus (HBV) or hepatitis C virus infection that requires treatment or at risk for HBV reactivation. At risk for HBV reactivation is defined as hepatitis B surface antigen positive or anti-hepatitis B core antibody positive. Participants with previous positive serology results must have negative polymerase chain reaction results.
• Patient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, New York Heart Association (NYHA) Grade ≥2 heart failure, uncontrolled hypertension, valvular disease, pericarditis, myocardial infarction, or other thrombosis events like including pulmonary embolism or deep vein thrombosis within 6 months of screening.
• Any other serious medical/psychiatric condition, in the judgement of the investigator, that likely to interfere or limit compliance with study requirements/treatment.

Sponsors & Collaborators

• Baptist Health South Florida: lead
• Incyte Corporation: collaborator

Study Sites (1)

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, 33176, United States

RECRUITING

Related Publications (5)

• Miller KD, Ostrom QT, Kruchko C, Patil N, Tihan T, Cioffi G, Fuchs HE, Waite KA, Jemal A, Siegel RL, Barnholtz-Sloan JS. Brain and other central nervous system tumor statistics, 2021. CA Cancer J Clin. 2021 Sep;71(5):381-406. doi: 10.3322/caac.21693. Epub 2021 Aug 24.

  PMID: 34427324 BACKGROUND

• Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.

  PMID: 15758009 BACKGROUND

• Cao Y, Lathia JD, Eyler CE, Wu Q, Li Z, Wang H, McLendon RE, Hjelmeland AB, Rich JN. Erythropoietin Receptor Signaling Through STAT3 Is Required For Glioma Stem Cell Maintenance. Genes Cancer. 2010 Jan 1;1(1):50-61. doi: 10.1177/1947601909356352.

  PMID: 20657792 BACKGROUND

• Guryanova OA, Wu Q, Cheng L, Lathia JD, Huang Z, Yang J, MacSwords J, Eyler CE, McLendon RE, Heddleston JM, Shou W, Hambardzumyan D, Lee J, Hjelmeland AB, Sloan AE, Bredel M, Stark GR, Rich JN, Bao S. Nonreceptor tyrosine kinase BMX maintains self-renewal and tumorigenic potential of glioblastoma stem cells by activating STAT3. Cancer Cell. 2011 Apr 12;19(4):498-511. doi: 10.1016/j.ccr.2011.03.004.

  PMID: 21481791 BACKGROUND

• Becker H, Engelhardt M, von Bubnoff N, Wasch R. Ruxolitinib. Recent Results Cancer Res. 2014;201:249-57. doi: 10.1007/978-3-642-54490-3_16.

  PMID: 24756798 BACKGROUND

Related Links

• Miami Cancer Institute

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

ruxolitinib; Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; 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

• Manmeet Ahluwalia, M.D., MBA

  Miami Cancer Institute at Baptist Health, Inc.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Manmeet Ahluwalia, M.D., MBA

CONTACT

(786) 596-2000; ManmeetA@baptisthealth.net

MCI Multisite Research Program

CONTACT

MCIMultisiteResearch@baptisthealth.net

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2025
• First Posted: May 25, 2025
• Study Start: December 3, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)