Details

Autor(en) / Beteiligte

• Rahman, Rifaquat
• Trippa, Lorenzo
• Fell, Geoffrey
• Lee, Eudocia
• Arrillaga-Romany, Isabel
• Touat, Mehdi
• McCluskey, Christine
• Brunno, Jennifer
• Gaffey, Sarah
• Drappatz, Jan
• Lassman, Andrew
• Galanis, Evanthia
• Ahluwalia, Manmeet
• Colman, Howard
• Nabors, Louis
• Hepel, Jaroslaw
• Elinzano, Heinrich
• Schiff, David
• Chukwueke, Ugonma
• Beroukhim, Rameen
• Nayak, Lakshmi
• Mcfaline-Figueroa, Jose
• Batchelor, Tracy
• Rinne, Mikael
• Kaley, Thomas
• Lu-Emerson, Christine
• Bi, Wenya Linda
• Arnaout, Omar
• Haas-Kogan, Daphne
• Tanguturi, Shyam
• Cagney, Daniel
• Aizer, Ayal A
• Welch, Mary
• Doherty, Lisa
• Lavallee, Maria
• Fisher-Longden, Brittany
• Dowling, Shanna
• Geduldig, Jack
• Watkinson, Fiona
• Santagata, Sandro
• Meredith, David
• Chiocca, E Antonio
• Reardon, David
• Ligon, Keith
• Alexander, Brian
• Wen, Patrick

Titel

CTNI-11. CC-115 IN NEWLY DIAGNOSED MGMT UNMETHYLATED GLIOBLASTOMA IN THE INDIVIDUALIZED SCREENING TRIAL OF INNOVATIVE GLIOBLASTOMA THERAPY (INSIGHT): A PHASE II RANDOMIZED BAYESIAN ADAPTIVE PLATFORM TRIAL

Ist Teil von

• Neuro-oncology (Charlottesville, Va.), 2020-11, Vol.22 (Supplement_2), p.ii43-ii44

Ort / Verlag

US: Oxford University Press

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract BACKGROUND CC-115 is an oral, CNS-penetrant, selective inhibitor of mammalian target of rapamycin kinase (mTOR) and deoxyribonucleic acid-dependent protein kinase (DNA-PK). Both targets are important in glioblastoma; PI3K/Akt/mTOR signaling is hyperactive in most glioblastomas, and DNA-PK is integral to repair of radiotherapy-mediated DNA damage. To investigate CC-115 in newly diagnosed glioblastoma and explore potential genomic biomarker associations, CC-115 was evaluated in the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) trial, an adaptive platform trial designed to efficiently test experimental agents. METHODS Adults with newly diagnosed MGMT-unmethylated glioblastoma, with genomic data available, are eligible for this ongoing trial. Patients are adaptively randomized to one of several experimental arms or the control arm: standard radiotherapy with concurrent and adjuvant temozolomide. The primary endpoint is overall survival (OS). Patients randomized to CC-115 (10mg po BID) received it concurrently with radiotherapy and as adjuvant monotherapy. As the first in-human use of CC-115 with radiation, a safety lead-in 3 + 3 design was used. RESULTS Twelve patients were randomized to CC-115; seven patients had possible treatment-related CTCAE grade > 3 toxicity, including four pre-specified dose-limiting toxicities: liver function abnormality (n=1), hyperlipidemia (n=1), lipase elevation (n=1) and cerebral edema (n=1). There was no significant difference in progression-free survival (PFS, median 4.2 months [CC-115] vs. 5.2 months, p=0.9) or OS (median 10.1 months [CC-115] vs. 14.5 months, p=0.9) compared to the 50 patients randomized to the control arm. Based on early PFS results, randomization probability to CC-115 decreased from 25% to < 10% at time of the trial arm closure. CONCLUSION Concurrent and adjuvant CC-115 was associated with toxicity and failed to improve PFS or OS. The INSIGhT trial design allowed for more efficient testing of CC-115, decreasing patients and resources allocated to a therapy that was discontinued due to concerns about toxicity and unfavorable risk-to-benefit ratio.