Artikel
Open-label phase 1 clinical trial testing personalised and targeted skull remodelling surgery to maximise TTFields intensity for recurrent glioblastoma – interim analysis and safety assessment (OptimalTTF-1)
Open-label Phase 1 Studie zur Untersuchung einer personalisierten und zielgerichteten Remodellierungsoperation zur Maximierung der TTFields Intensität beim rezidivierenden Glioblastom – Interim Analyse und Sicherheitsbewertung (OptimalTTF-1)
Suche in Medline nach
Autoren
Veröffentlicht: | 8. Mai 2019 |
---|
Gliederung
Text
Objective: We present a pre-specified interim analysis of an ongoing open-label, investigator-sponsored phase 1 trial (NCT02893137) testing safety/efficacy of a new rGBM treatment. The intervention combines personalized skull-remodeling (SR) surgery with TTFields and best-choice chemotherapy. SR-surgery involves minor craniectomy, burr-holes, and/or skull thinning personalized to enhance TTFields intensity focally in the tumor.
Methods: Eligibility: Age >18 years, first recurrence focal supratentorial GBM (RANO), and KPS ≥70. Personalized electric field calculations were conducted to validate TTFields enhancement > 25% by SR-surgery. Patients were right-censored for OS and PFS at the time of analysis and excluded upon progression, death, SUSARs, or unacceptable AEs. Primary endpoints: Toxicity (CTCAEv4.0). Secondary endpoints: OS, PFS, PFS6, objective response rate (iRANO), quality of life, KPS, and steroid dose.
Results: 16 patients were screened, 1 declined, and 2 had KPS<70. Of the 13 enrolled patients, 3 were excluded prior to TTFields treatment (1 female due to radionecrosis/non-recurrence, 1 male due to post-op infection, and 1 female due to neurological deficits). All included patients (9 male and 1 female) had GBM IDH-wt tumors (4 MGMT-methylated). Median age was 55 years (range 49 to 67). All patients received maximum safe resection at recurrence (4 had no residual tumor (RANO), 4 had non-measurable disease, and 2 had measurable disease). 8 patients received adjuvant bevacizumab monotherapy and 2 received temozolomide rechallenge. The mean skull-defect area was 10.5 cm2, the median field enhancement 37%. Within the observation period 5 patients had progression, 3 died, 5 were censored for PFS, and 7 for OS. We observed no SUSARs or grade 4/5 SAEs, but 5 grade 3 SAEs (2 generalized seizures in patients with known epilepsy, 1 post-op infection, 1 diarrhea, and 1 DVT). 2 patients had grade 1–2 skin rash, and 1 had grade 1–2 headaches. Median OS was 15.5 months, 95%-CI: 5.9-NA, median PFS 9.5 months, 95%-CI: 3.7-NA, and PFS6 58%, 95%-CI: 0.27–0.90. 1 patient had complete response during TTFields treatment.
Conclusion: SR-surgery including craniectomy is not associated with additional toxicity in combination with TTFields and holds promising potential for improving TTFields outcome by focally enhancing the field intensity in the tumor. A future phase 2/3 trial is being planned for efficacy assessment.