scholarly journals CTNI-74. PHASE 3 TRIDENT TRIAL: CONCOMITANT RADIATION THERAPY (RT) AND TEMOZOLOMIDE +/- TUMOR TREATING FIELDS (TTFIELDS) IN NEWLY DIAGNOSED GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii59-ii60
Author(s):  
Wenyin Shi ◽  
Lawrence Kleinberg ◽  
Suriya A Jeyapalan ◽  
Samuel Goldlust ◽  
Seema Nagpal ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Type I ◽  
Newly Diagnosed ◽  
Phase 3 ◽  
Free Survival ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND Tumor treating fields (TTFields) is a non-invasive, regional antimitotic treatment approved as a standard-of-care for newly diagnosed glioblastoma (ndGBM). In the EF-14 Phase 3 trial, TTFields (200 kHz) plus temozolomide (TMZ) significantly increased survival of ndGBM patients without increasing systemic toxicity. TTFields-related AEs were mainly skin AEs. In preclinical models, TTFields increase the therapeutic effects of radiation therapy (RT). A pilot study showed that TTFields concomitant with RT and TMZ is well tolerated. The benefit of concomitant TTFields with RT and TMZ will be tested in the TRIDENT trial. METHODS TRIDENT is an international phase III randomized trial comparing standard RT with TMZ vs the triple combination of RT/TMZ with concomitant TTFields. RT is delivered through the TTFields arrays. Patients in both arms will receive maintenance TTFields/TMZ. TTFields (200 KHz) will be delivered >18 hours/day using Optune. Patients will continue TTFields treatment until second recurrence. Patients with pathologically confirmed ndGBM, ≥ 18 years, KPS ≥ 70, either sex, post-surgery or biopsy, and amenable for RT/TMZ therapy will be stratified by extent of resection and MGMT promoter methylation status. The primary endpoint is overall survival (OS). Secondary end points: progression free survival (PFS; RANO), 1- and 2-year survival rates, overall radiological response (ORR; RANO), progression-free survival (PFS6M, PF12M, PFS2Y); severity and frequency of AEs (CTCAE V5.0); pathological changes in resected GBM tumors post treatment; quality of life (EORTC QLQ-C30); and correlation of OS to TTFields compliance. The hypothesis is that concomitant TTFields/RT/TMZ will significantly improve OS versus RT/TMZ. Sample size (N=950; 475/arm) will detect a HR< 0.8 with 5% type I error. Survival will be measured from the time of randomization until date of death. At the time of analysis, patients lost to follow-up or still on protocol follow-up will be censored at the last date known to be alive.

scholarly journals ES-2 Phase 3 TRIDENT Trial: Radiation and Temozolomide with or without Tumor Treating Fields in newly diagnosed glioblastoma

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii3-ii3
Author(s):  
Mitsutoshi Nakada
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Therapeutic Effects ◽  
Type I ◽  
Newly Diagnosed ◽  
Phase 3 ◽  
Free Survival ◽  
Tumor Treating Fields ◽  
Post Surgery

Abstract Background: Tumor treating fields (TTFields) is a non-invasive, regional antimitotic treatment approved as a standard-of-care for glioblastoma. In the EF-14 Phase 3 trial, TTFields (200 kHz) plus temozolomide (TMZ) significantly increased survival of patients with newly diagnosed GBM(ndGBM) without increasing systemic toxicity. TTFields-related AEs were mainly skin AEs. In preclinical models, TTFields increase the therapeutic effects of radiation therapy (RT). A pilot study showed that TTFields concomitant with RT and TMZ is well tolerated. The benefit of concomitant TTFields with RT and TMZ will be tested in the TRIDENT trial. Methods: TRIDENT is an international phase III randomized trial comparing standard RT/TMZ vs the triple combination of RT/TMZ with concomitant TTFields. RT is delivered through the TTFields arrays. Patients in both arms will receive maintenance TTFields/TMZ. TTFields (200 kHz) will be delivered over18 hours/day using Optune. Patients will continue TTFields treatment until second recurrence. Patients with pathologically confirmed ndGBM, over 18 years old, KPS over 70, either sex, post-surgery or biopsy, and amenable for RT/TMZ therapy will be stratified by extent of resection and MGMT promoter methylation status. The primary endpoint is overall survival (OS). Secondary end points: progression free survival (PFS; RANO), 1- and 2-year survival rates, overall radiological response (ORR; RANO), progression-free survival (PFS2, PFS6, PFS12); severity and frequency of AEs (CTCAE V5.0); pathological changes in resected GBM tumors post treatment; quality of life (EORTC QLQ-C30); and correlation of OS to TTFields compliance. The hypothesis is that concomitant TTFields/RT/TMZ will significantly improve OS versus RT/TMZ. Sample size (N=950; 475/arm) will detect a HR lower than 0.8 with 5% type I error. Survival will be measured from the time of randomization until date of death. At the time of analysis, patients lost to follow-up or still on protocol follow-up will be censored at the last date known to be alive.

Phase III TRIDENT trial: Radiation and temozolomide +/- tumor treating fields in newly diagnosed glioblastoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS2580-TPS2580
Author(s):  
Wenyin Shi ◽  
Lawrence Kleinberg ◽  
Suriya A. Jeyapalan ◽  
Samuel Aaron Goldlust ◽  
Seema Nagpal ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Therapeutic Effects ◽  
Type I ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Tumor Treating Fields ◽  
Post Surgery

TPS2580 Background: Tumor treating fields (TTFields) is a non-invasive, regional antimitotic treatment approved as a standard of care for glioblastoma (GBM). In the EF-14 phase III trial, TTFields (200 kHz) plus temozolomide (TMZ) significantly increased the survival of patients with newly diagnosed GBM (ndGBM) without increase in systemic toxicity. TTFields-related AEs were mainly skin AEs. In preclinical models, TTFields increase the therapeutic effects of radiation therapy (RT). A pilot study showed that TTFields concomitant with RT and TMZ is well tolerated. The benefit of concomitant TTFields with RT and TMZ will be tested in this phase III TRIDENT randomized trial. Methods: TRIDENT is an international phase III randomized trial comparing standard RT with TMZ vs the triple combination of RT plus TMZ with concomitant TTFields. RT is delivered through the TTFields arrays. Patients in both arms will receive maintenance TTFields with TMZ. TTFields (200 KHz) will be delivered >18 hours/day using Optune. Patients will continue TTFields treatment until second recurrence. Patients with pathologically confirmed newly ndGBM, ≥ 18 years, KPS ≥ 70, either sex, post-surgery or biopsy, who are amenable for RT/TMZ therapy will be enrolled. Patients will be stratified by extent of resection and MGMT promoter methylation status. The primary endpoint is overall survival (OS). Secondary end points include: progression free survival (PFS; RANO), 1- and 2-year survival rates, overall radiological response (ORR; RANO), progression-free survival (PFS2, PFS6, PFS12); severity and frequency of AEs (CTCAE V5.0); pathological changes in resected GBM tumors post treatment; quality of life (EORTC QLQ-C30); and correlation of OS to TTFields compliance. The hypothesis is that concomitant TTFields with radiation and TMZ will significantly improve OS as compared to radiation and TMZ alone. The sample size is 950, with 475 in each arm to detect a HR <0.8 with a 5% type I error. Survival will be measured from the time of randomization until date of death. At the time of analysis, patients who are lost to follow-up or still on protocol follow-up will be censored at the last date known to be alive.

scholarly journals P14.79 Randomized phase II trial of Tumor Treating Fields plus radiation therapy plus temozolomide compared to radiation therapy plus temozolomide in patients with newly diagnosed glioblastoma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii86-iii86
Author(s):  
D Limon ◽  
F Bokstein ◽  
D Blumenthal ◽  
C Ben Harush ◽  
Z Ram ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Pilot Study ◽  
Surgical Resection ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Tumor Treating Fields ◽  
Randomized Phase Ii

Abstract BACKGROUND In last decade, there were numerous attempts to improve the outcome of patients with glioblastoma (GBM), but even after maximal surgical resection, radiation therapy (RT) and temozolomide (TMZ), followed by maintenance TMZ for 6 months the median OS is 14.6 months. In the EF-14 Phase III trial, the addition of Tumor Treating Fields (TTFields) at 200 kHz to maintenance TMZ increased the median OS to 20.9 months, compared with 16.0 months with maintenance TMZ alone (HR, 0.63; 95% CI, 0.53–0.76; p<0.001). Based on these results, the currently accepted standard of care for newly diagnosed GBM (ndGBM) is surgical resection if safely feasible, followed by RT with concomitant TMZ, and then followed by maintenance TMZ in combination with TTFields. Preclinical investigations have shown a radio-sensitizing effect of TTFields on glioma cells, suggesting synergistic effects between TTFields and radiotherapy. In a pilot study of 10 patients with ndGBM, we demonstrated that there was no increased treatment-related toxicity when TTFields were given in combination with RT/TMZ. The only TTFields-related adverse event was skin toxicity below the arrays. Preliminary progression free survival (PFS) data was encouraging. Based on the results of the pilot study, we designed this prospective, randomized Phase II study to further investigate if the addition of TTFields TMZ/RT treatment in ndGBM patients improves treatment efficacy and delays disease progression. MATERIAL AND METHODS Following debulking surgery or biopsy, 60 adult patients (≥18 years) with histologically confirmed GBM, KPS≥70 and life expectancy of at least 3 months will be randomized 1:1 to either a) RT with concomitant TMZ and TTFields (200 kHz) for 6 weeks followed by up to 6 months of maintenance TMZ in combination with TTFields (experimental arm) up to 24 months; or b) RT with concomitant TMZ alone followed by maintenance TMZ in combination with TTFields (control arm). Exclusion criteria: patients with early progressive disease, significant comorbidities precluding maintenance RT or TMZ or patients with an implanted electronic device. The primary endpoint is progression free survival at 12 months (PFS12). Treatment with TTFields will be continued until second progression or 24 months (the earlier of the two). All patients will be followed for survival. Grading and severity of all adverse events will be recorded using CTCAE V5.0. The sample size of 60 patients provides 80% power with a two-sided alpha level of 0.05 to detect a PFS12 of 46.5% with RT/TMZ/TTFields compared to 29.4% with RT/TMZ followed, respectively, by maintenance TMZ/TTFields (calculated from the RT/TMZ followed by maintenance TMZ/TTFields arm of the EF-14 trial). It is forecasted to take 24 months to fully recruit. Follow-up will continue for >12 months from recruitment of the last patient.

scholarly journals P14.71 Tumor Treating Fields combined with radiotherapy and temozolomide for newly diagnosed glioblastoma: final safety and efficacy results from a pilot study

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii84-iii84
Author(s):  
R Grossman ◽  
F Bokstein ◽  
D Blumenthal ◽  
C Ben Harush ◽  
D Limon ◽  
...  
Keyword(s):  
Pilot Study ◽  
Electric Fields ◽  
Randomized Study ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma ◽  
Sensitizing Effect

Abstract BACKGROUND Tumor Treating Fields (TTFields) are a non-invasive, loco-regional, anti-mitotic treatment consisting of low intensity alternating electric fields. The combination of TTFields with maintenance temozolomide significantly improved survival versus temozolomide alone in the phase 3 EF-14 study in newly diagnosed glioblastoma (ndGBM). In preclinical studies, TTFields increased the number of glioma cells undergoing cellular death following radiotherapy (RT) by inhibiting DNA damage repair, suggesting a radio-sensitizing effect of TTFields. This pilot study is the first to evaluate the safety and feasibility of administering TTFields concomitant to RT and TMZ in ndGBM patients. MATERIAL AND METHODS Patients diagnosed with ndGBM were treated with TTFields/RT/TMZ followed by maintenance TMZ and TTFields for up to 24 months. TTFields (200kHz) were delivered for >18 hours/day while the transducer arrays were removed during delivery of RT. TMZ was administered at a dose of 75 mg/m2/daily for 6 weeks and RT at a total dose of 60 Gy. The primary endpoint was safety of the combined TTFields/RT/TMZ; secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicity. Adverse events (AEs) were graded according to CTCAE V4.0. RESULTS 10 ndGBM patients that recovered from maximal debulking surgery or biopsy were enrolled at a single center in Israel between April and December 2017. Five patients (50%) had undergone gross total resection while the rest had biopsy only. Eight of the patients were male, median age was 59, median KPS was 80 and median dose of RT was 60 Gy. Six patients (60%) reported at least one AE. The most common AE was TTFields-related skin toxicity, reported in four patients (40%), all of which were grade 1–2 in severity. Two patients reported serious AEs (seizures and general deterioration) that were considered unrelated to TTFields. Median PFS with RT/TMZ/TTFields was 10.5 months. Median OS has not yet been reached. CONCLUSION The proportion of patients with TTFields-related skin toxicity was similar to that reported in ndGBM patients in the randomized Phase III study (52%), where patients started TTFields at least 4 weeks after RT. No other TTFields-related toxicities were reported and there were no increase in RT- or TMZ-related toxicities as a result of combining TTFields with RT in addition to TMZ. Based on the safety and preliminary efficacy results of this pilot study, a phase II randomized study has been initiated to investigate the efficacy of concomitant RT/TMZ/TTFields in 60 ndGBM patients.

A Prospective, Randomized, Phase III Study of Bortezomib, Melphalan, Prednisone and Thalidomide (VMPT) Versus Bortezomib, Melphalan and Prednisone (VMP) in Elderly Newly Diagnosed Myeloma Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 652-652 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Davide Rossi ◽  
Valeria Magarotto ◽  
Francesco Di Raimondo ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Chromosomal Abnormalities ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Gastrointestinal Complications ◽  
Free Survival ◽  
Weekly Infusion ◽  
Grade 3

Abstract Background: In newly diagnosed myeloma patients the combination of bortezomib with melphalan-prednisone (VMP) was superior to MP. In relapsed-refractory patients the 4 drug combination of bortezomib-melphalan-prednisone-thalidomide (VMPT) induced a high proportion of complete responses (CR). Methods: Newly diagnosed myeloma patients (N=393) older than 65 years, from 58 centers in Italy, were randomly assigned to receive VMPT (N=193) or VMP (N=200). Initially, patients were treated with nine 6-week cycles of VMPT (bortezomib 1.3 mg/m2 days 1,4,8,11,22,25,29,32 in cycles 1–4 and days 1,8,22,29 in cycles 5–9; melphalan 9 mg/m2 days 1–4; prednisone 60 mg/m2 days 1–4 and thalidomide 50 mg days 1–42, followed by bortezomib 1.3 mg/m2 every 15 days and thalidomide 50 mg/day as maintenance) or VMP (bortezomib, melphalan and prednisone at the same doses and schedules previously described without maintenance). In March 2007, the protocol was amended: both VMPT and VMP schedules were changed to nine 5-week cycles and bortezomib schedule was modified to weekly administration (bortezomib 1.3 mg/m2 days 1,8,15,22 in cycles 1–9). Primary end-point was progression-free survival (PFS). Results: Patient characteristics were similar in both groups: median age was 71 years, 23% of patients were aged > 75 years. Patients who received at least 1 cycle were evaluated: 152 patients for VMPT (62 received bortezomib bi-weekly infusion and 90 weekly infusion) and 152 patients for VMP (62 received bortezomib bi-weekly infusion and 90 weekly infusion). Data were analyzed in intention-to-treat. The very good partial response (VGPR) rate was higher in the VMPT group (55% versus 42%, p=0.02), including a CR rate of 31% in the VMPT group and 16% in the VMP group (p=0.003). In the subgroup treated with weekly infusion of bortezomib, VGPR was 59% for VMPT and 37% for VMP (p=0.004), including 28% CR for VMPT and 10% for VMP (p=0.004). Subgroup analyses did not show any statistical difference between responses and either age, B2-microglobulin or chromosomal abnormalities, such as del13, t(4;14), t(14;16) and del17. After a median follow-up of 13.6 months, the 2-year PFS was 83.9% in the VMPT group and 75.7% in the VMP group (HR=0.73, 95% CI 0.38–1.42, p=0.35). In patients who received weekly infusion of bortezomib, the 2-year PFS was 86.8% in the VMPT group and 78.1% in the VMP group (HR=0.65, 95% CI 0.24–1.8, p=0.41). In patients who achieved CR after induction, the 2-year PFS was 100% for VMPT and 79% for VMP (p=0.02). The 3-year overall survival (OS) was 89.5% in the VMPT group and 88.7% in the VMP group (HR=1.02, 95% CI 0.43–2.46, p=0.96). The incidence of grade 3–4 adverse events (AEs) was similar in both groups. In the VMPT patients and in the VMP patients, the more frequent AEs were neutropenia (36% vs 31%), thrombocytopenia (20% vs 19%), peripheral neuropathy (18% vs 12%), infections (14% vs 10%), and gastrointestinal complications (7% vs 8%), respectively. The weekly infusion of bortezomib significantly decreased the incidence of grade 3–4 peripheral neuropathy (9% for VMPT and 3% for VMP). Conclusion: VMPT is superior to VMP in terms of response rates. Longer follow-up is needed to assess their effects on PFS and OS. The weekly infusion of bortezomib significantly reduced the incidence of grade 3–4 peripheral neuropathy without influencing outcome. Table. Complete responses, progression-free survival and peripheral neuropathy in all patients and in those who received weekly infusion of bortezomib VMPT group (n=152) VMP group (n=152) All patients (n=152) Subgroup with bortezomib weekly infusion (n=90) All patients (n=152) Subgroup with bortezomib weekly infusion (n=90) CR rate (%) 31 28 16 10 2-year PFS (%) 84 87 76 78 Grade 3–4 peripheral neuropathy (%) 18 9 12 3

Updated safety/feasibility study of concurrent tumor treating fields (TTFields) and radiation therapy for newly diagnosed glioblastoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14535-e14535
Author(s):  
Rachel Grossman ◽  
Felix Bokstein ◽  
Deborah T. Blumenthal ◽  
Dror Limon ◽  
Carmit Ben Harush ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Pilot Study ◽  
Electric Fields ◽  
Tumor Resection ◽  
Skin Toxicity ◽  
Phase Iii ◽  
Karnofsky Performance Score ◽  
Newly Diagnosed ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma

e14535 Background: Tumor Treating Fields (TTFields), a non-invasive, loco-regional, anti-mitotic treatment comprises low-intensity alternating electric fields. In the phase III EF-14 study in newly diagnosed glioblastoma (ndGBM), TTFields in combination with temozolomide (TMZ) significantly improved survival compared to TMZ alone. In preclinical studies TTFields had a radiosensitizing effect and increased the efficacy of radiation therapy (RT). This pilot study [NCT03780569] evaluated the feasibility and safety of TTFields administered concurrently with RT and TMZ in ndGBM patients. Methods: Patients with histologically confirmed ndGBM were treated with TTFields/RT/TMZ followed by adjuvant TMZ/TTFields. TTFields (200 kHz) were delivered for ≥18 hours/day with transducer arrays removed during RT delivery. RT was administered to the tumor bed in 30 fractions (total dose 60 Gy) in combination with daily TMZ (75 mg/m2). In the adjuvant phase, patients received monthly TMZ (150–200 mg/m2 for 5 days) plus TTFields. The primary outcome was safety of the combined therapies; secondary outcomes included progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were graded per CTCAE v4.0. Results: Ten patients were enrolled at a single center between April and December 2017. Median age was 60.2 years, median Karnofsky Performance Score was 90.0, and eight (80%) patients were male. Five (50%) patients had undergone tumor resection while the remainder had biopsy only. Eight patients experienced ≥1 RT treatment delay; delays were unrelated to TTFields treatment. All patients experienced ≥1 AE. Three patients suffered from serious AEs (urinary tract infection, confusional state, and decubitus ulcer) that were considered unrelated to TTFields. The most common AE was skin toxicity, reported in eight (80%) patients; all were of low severity (CTCAE grade 1–2) and were reported as related to TTFields treatment. Median PFS from enrollment was 8.9 months; median OS was not reached at the time of study closure. Conclusions: Eighty percent of patients experienced grade 1–2 TTFields-related skin toxicity. No other TTFields-related toxicities were observed and there was no increase in RT- or TMZ-related toxicities as a result of combining TTFields with these therapies. Based on the safety and preliminary efficacy results of this pilot study, a phase 2 randomized trial (N = 60; NCT03869242) and the Phase 3 TRIDENT trial have been initiated to further investigate the efficacy of concomitant RT/TMZ/TTFields in ndGBM. Clinical trial information: NCT03780569.

scholarly journals CTNI-38. PriCoTTF TRIAL: A PHASE I/II TRIAL OF TTFIELDS PRIOR AND CONCOMITANT TO RADIOTHERAPY IN NEWLY DIAGNOSED GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi68-vi68
Author(s):  
Sied Kebir ◽  
Daniela Pierscianek ◽  
Martin Proescholdt ◽  
Peter Hau ◽  
Anca-Ligia Grosu ◽  
...  
Keyword(s):  
Phase I ◽  
Survival Rates ◽  
Progression Free Survival ◽  
The Elderly ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Safety And Efficacy ◽  
Fractionated Radiotherapy ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma

Abstract TTFields therapy is applied at 200 kHz by arrays that are placed at the patients’ scalp. In the phase 3 EF-14 trial, survival rates were significantly improved when adding tumor-treating fields (TTFields) to adjuvant temozolomide-based chemotherapy in patients with newly diagnosed glioblastoma (nGBM). Preclinical studies showed that combination of TTFields and radiotherapy synergistically impaired glioblastoma cell growth. Here, we present the PriCoTTF trial, which is enrolling nGBM patients and will assess the safety and efficacy of TTFields initiated prior and concomitant to radiochemotherapy. Following surgery and wound-healing, TTFields therapy is initiated in adult nGBM patients. TTFields therapy continues throughout radiochemotherapy and adjuvant chemotherapy for a total of approximately 9 months. During radiotherapy, the arrays - through which TTFields is delivered - remain on the patients’ scalp. Totally, thirty-three patients are planned to be enrolled in two treatment arms. In arm A, 20 patients receive normo-fractionated radiotherapy, whereas in the elderly arm, arm B, 13 patients receive hypo-fractionated radiotherapy. The primary endpoint of this trial is safety and tolerance that will be gauged by a set of pre-specified treatment-limiting toxicities. Secondary endpoints include the frequency of adverse events, progression-free survival (PFS), and overall survival (OS). The trial is currently enrolling patients at four sites in Germany. At the time of abstract submission, 9 patients enrolled in Arm B. Patient recruitment for arm A has been completed with. We will present initial practical experiences as well as preliminary safety and tolerance data. There is a biological rationale for combining TTFields and radiotherapy to further improve survival of GBM patients. In the presented phase I/II trial, the safety and efficacy of TTFields initiated prior and concomitant to RT in nGBM will be assessed. In addition, initial efficacy data (phase II) may serve as a rationale for a putative randomized phase III trial.

scholarly journals RTID-12. PHASE 2 TRIAL OF TUMOR TREATING FIELDS (TTFIELDS) PLUS RADIATION THERAPY (RT) PLUS TEMOZOLAMIDE (TMZ) COMPARED TO RT PLUS TEMOZOLOMIDE IN NEWLY DIAGNOSED GLIOBLASTOMA (ndGBM)

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii196-ii196
Author(s):  
Rachel Grossman ◽  
Dror Limon ◽  
Felix Bokstein ◽  
Carmit Ben Harosh ◽  
Deborah Blumenthal ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Skin Toxicity ◽  
Phase 2 ◽  
Free Survival ◽  
Tumor Treating Fields ◽  
Phase 2 Trial ◽  
Phase 2 Study ◽  
Newly Diagnosed Glioblastoma ◽  
Early Progressive Disease

Abstract OBJECTIVE In the EF-14 phase 3 trial, TTFields 9200 kHz) added to maintenance TMZ increased median OS to 20.9 months versus 16.0 months with maintenance TMZ (p&lt; 0.001) in ndGBM. Preclinical investigations showed that TTFields/RT have a synergistic effect. A pilot study (N=10) in ndGBM demonstrated the feasibility and safety of TTFields combined with RT/TMZ (Grossman Front Onc 2020). The only TTFields-related adverse event was array-associated skin toxicity. Median PFS was 8.9 months. Based on these encouraging results, this prospective, randomized phase 2 study [NCT03869242] in 60 patients further investigates if the addition of TTFields TMZ/RT treatment in ndGBM patients improves treatment efficacy and delays disease progression. METHODS Following debulking surgery or biopsy, 60 patients (≥18 years) with histologically confirmed GBM, KPS≥70 and life expectancy &gt;3 months will be randomized 1:1 to: i) RT with concomitant TMZ/TTFields (200 kHz) for 6 weeks followed by up to 6 months of maintenance TMZ combined with TTFields (experimental arm) up to 24 months; or ii) RT with concomitant TMZ alone followed by maintenance TMZ combined with TTFields (control arm). Patients with early progressive disease, significant comorbidities precluding maintenance RT or TMZ or with implanted electronic devices will be excluded. The primary endpoint is the rate of progression free survival at 12 months (PFS12). Treatment with TTF will be continued until second progression or 24 months (the earlier of the two). All patients will be followed for survival. All adverse events will graded per CTCAE V5.0. The sample size of 60 patients provides 80% power with two-sided alpha level of 0.05 to detect a PFS12 of 46.5% with RT/TMZ/TTFields compared to 29.4% with RT/TMZ followed, respectively, by maintenance TMZ/TTFields (calculated from the RT/TMZ followed by maintenance TMZ/TTFields arm of the EF-14 trial). Follow-up will continue for &gt;12 months from recruitment of the last patient.

The addition of bevacizumab to temozolomide and radiation therapy followed by bevacizumab, temozolomide, and oral topotecan for newly diagnosed glioblastoma multiforme (GBM).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2090-2090 ◽  
Author(s):  
Henry S. Friedman ◽  
Annick Desjardins ◽  
Katherine B. Peters ◽  
David A. Reardon ◽  
John Kirkpatrick ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Wound Dehiscence ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Anti Epileptic Drug ◽  
Aortic Thrombus ◽  
Phase Iii Trials ◽  
Newly Diagnosed Glioblastoma ◽  
Oral Topotecan

2090^ Background: The prognosis for newly-diagnosed GBM is dismal. The addition of temozolomide to radiation therapy improved the median overall survival (OS) to 14.6 months (mos). GBM’s have the highest levels of vascular endothelial growth factor (VEGF). Hypoxia inducing factor-1 alpha (HIF-1 alpha) is an important regulator of VEGF, and topotecan may inhibit HIF-1 alpha. Methods: We performed a phase II trial in newly diagnosed GBM by adding bevacizumab and topotecan to standard therapy. 80 newly diagnosed GBM patients were enrolled between January 2010 and January 2011. Patients received standard radiation therapy and temozolomide. Bevacizumab at 10 mg/kg every 14 days was added a minimum of 4 weeks post-op. Two weeks after radiation therapy was completed, 12 monthly cycles of temozolomide at 150 mg/m2 /d days 1-5, oral topotecan at 1.5 mg/m2 for patients not on an enzyme inducing anti-epileptic drug (EIAED) and 2.0 mg/m2 for patients on an EIAED days 2-6, and bevacizumab at 10 mg/kg on days 1 and 15. Results: The addition of bevacizumab to standard radiation therapy and daily temozolomide was safe. Of the 80 patients, 76 completed radiation therapy. Four patients did not complete radiation, two with clinical decline, one each with a bone flap infection, and a pulmonary embolus. Fifteen patients came off study for toxicity, five with recurrent grade IV thrombocytopenia, three with grade III fatigue, two each with grade 2 CNS hemorrhage, and wound dehiscence requiring surgery and one each with GI perforation, pulmonary embolism and an aortic thrombus. Of the 80 patients, 56 have progressed and 37 have died. The median progression-free survival (PFS) and OS are 11.1 mos (95% CI: 9.4-13.6) and 17.2 mos (95% CI: 15.2) at a median follow-up of 18.4 months. The two year OS is 45.3%. Conclusions: The addition of bevacizumab to temozolomide and radiation followed by temozolomide, bevacizumab and oral topotecan is tolerable. The median PFS and OS are encouraging. The randomized phase III trials with bevacizumab for newly diagnosed GBM patients are essential.

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