scholarly journals 952 Phase II trial of AV-GBM-1: dendritic cell vaccine pulsed with lysate enriched for autologous tumor-initiating cell antigens in the treatment of patients with newly diagnosed glioblastoma

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A1001-A1001
Author(s):  
Daniela Bota ◽  
David Piccioni ◽  
Christopher Duma ◽  
Renato LaRocca ◽  
Santosh Kesari ◽  
...  
Keyword(s):  
Phase Ii ◽  
Standard Therapy ◽  
Randomized Trials ◽  
Progression Free Survival ◽  
Cell Vaccine ◽  
Autologous Tumor ◽  
Newly Diagnosed ◽  
Eligibility Criteria ◽  
Free Survival ◽  
Gm Csf

BackgroundStandard therapy of glioblastoma (GBM), which includes maximum safe resection, concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ) followed by maintenance TMZ, is associated with poor overall survival (OS). Adding treatment with AV-GBM-1, a vaccine consisting of autologous dendritic cells (DC) pulsed with autologous tumor antigens (ATA) may improve OS. A multi-center phase II clinical trial was conducted to determine feasibility, safety, and efficacy of AV-GBM-1.MethodsKey eligibility criteria for tumor collection were clinical suspicion of newly diagnosed GBM and age 18 to 70 years at the time of surgery. Prior to starting RT/TMZ, key eligibility criteria for intent-to-treat-with-AV-GBM-1 enrollment were: (1) primary GBM confirmed, (2) successful GBM cell culture, (3) collection of sufficient numbers of monocytes (MC) by leukapheresis, (4) Karnofsky Performance Status 70 or greater and (5) plan to treat with concurrent RT/TMZ. AV-GBM-1 was manufactured during RT/TMZ. Interleukin-4 and granulocyte-macrophage colony stimulating factor (GM-CSF) were used to differentiate MC into DC. AV-GBM-1 consists of autologous DC incubated with ATA from the lysate of irradiated GBM cells grown in serum-free media with factors that favor the survival and proliferation of stem cells and early progenitor cells. After recovery from RT/TMZ, over six months patients received up to 8 subcutaneous injections of AV-GBM-1 admixed with 500 μg GM-CSF. The primary objective was to determine if OS was 75% or higher 14.6 months from ITT enrollment, which ended January 2020. The minimum follow-up at the time of analysis was 15.2 months. Secondary endpoints included progression-free survival (PDS) from ITT enrollment and from the first injection.ResultsSuccess rates for cell cultures and sufficient monocyte collections were both 97%. AV-GBM-1 was manufactured for 60/60 (100%). 57 patients received 392 injections; 68% received all 8. The primary adverse events (AE) attributed to AV-GBM-1 were local injection site reactions (16%) and flu-like symptoms (10%). Progression-free survival (PFS) from ITT enrollment is 10.3 months, about 50% longer than reported in four randomized trials with comparable standard therapy arms. PFS from the first injection is 8.3 months, which is 51% and 107% longer than reported in two randomized trials with comparable standard therapy arms. OS was 72% at 12 months, but dropped to 54% at 14.6 months; median OS is 16.0 months.ConclusionsPatent-specific AV-GBM-1 was reliably manufactured and distributed for administration. AV-GBM-1 produced minimal toxicity. PFS was very encouraging but did not translate into OS, perhaps because of discontinuation of treatment after 8 months.Trial Registration[Clinicaltrials.gov NCT03400917]Ethics ApprovalWestern IRB, approval number 20182582Consent n/a

scholarly journals 331 Tumor markers associated with increased survival in a phase II trial of dendritic cell/tumor-initiating-cell vaccine AV-GBM-1 in patients with newly diagnosed glioblastoma

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A357-A357
Author(s):  
Daniela Bota ◽  
David Piccioni ◽  
Christopher Duma ◽  
Renato LaRocca ◽  
Santosh Kesari ◽  
...  
Keyword(s):  
Phase Ii ◽  
Dna Methyltransferase ◽  
Karnofsky Performance Status ◽  
Interleukin 4 ◽  
Cell Vaccine ◽  
Autologous Tumor ◽  
Idh Mutation ◽  
Newly Diagnosed ◽  
Aggressive Therapy ◽  
Gm Csf

BackgroundStandard aggressive therapy of glioblastoma (GBM), which includes maximum safe resection, concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ) followed by maintenance TMZ, is associated with a 25% 2-year overall survival (OS). Adding treatment with AV-GBM-1, a vaccine consisting of autologous dendritic cells (DC) pulsed with autologous tumor antigens (ATA) may improve OS by inducing and/or enhancing the host anti-GBM immune response. Methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter, and mutation of the gene for isocitrate dehydrogenase (IDH) are favorable prognostic markers in newly diagnosed GBM. An objective of a multi-center phase II clinical trial was to determine whether these markers were still prognostic for OS in patients treated with adjunctive AV-GBM-1.MethodsKey eligibility criteria for intent-to-treat (ITT) enrollment were: (1) confirmation of primary GBM, (2) successful GBM cell culture, (3) collection of sufficient numbers of monocytes (MC) by leukapheresis, (4) Karnofsky Performance Status 70 or greater after recovery from surgery, and (5) plan to treat with concurrent RT/TMZ. AV-GBM-1 was manufactured while patients were being treated with RT/TMZ. Interleukin-4 and granulocyte-macrophage colony stimulating factor (GM-CSF) were used to differentiate DC from MC. Each vaccine consisted of autologous DC incubated with ATA from the lysate of irradiated cultured GBM cells grown in serum-free media with factors that favor survival and proliferation of stem cells and early progenitor cells (tumor-initiating cells). After recovery from RT/TMZ, intent was to vaccinate for up to six months with cryopreserved AV-GBM-1 admixed with 500 mg GM-CSF. All patients had testing for MGMT-methylation and IDH-mutation. OS was calculated from date of ITT enrollment.Results60 patients were enrolled during August 2018 to January 2020. MGMT promoter methylation was detected in 21 (35%), mutated IDH in 7 (12%), and one or both in 25 (42%). At a minimum follow-up of 15 months, median OS had not been reached for patients with a methylated MGMT promotor, IDH mutation, or one or both, compared to 14.6 months for 38 with unmethylated MGMT promotor (p=0.026), 14.7 months for 53 with IDH wild-type (p=0.044), and 14.6 months for 35 who had neither (p=0.017). 18-month OS rates were 59% vs 35% for MGMT promotor methylation, 71% vs 40% for IDH mutation and 58% vs 32% for either.ConclusionsBoth MGMT promotor methylation and IDH mutation were associated with a substantial and similar survival benefit in primary GBM patients treated with AV-GBM-1 in addition to standard aggressive therapy.Trial RegistrationClinicaltrialsgov NCT03400917Ethics ApprovalThis study was approved by the Western IRB, approval number 20182582; all participants gave written informed consent before taking part

Full Dose Vincristine (V) Negatively Impacts Progression Free Survival in Newly Diagnosed or Relapsed/Refractory Multiple Myeloma Patients Treated with Pegylated Doxorubicin, Vincristine, Reduced-Dose Dexamethasone, and Thalidomide (DVd-T).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2570-2570
Author(s):  
R. Suppiah ◽  
E. Walker ◽  
K. Almhanna ◽  
S. Andresen ◽  
J. Reed ◽  
...  
Keyword(s):  
Phase Ii ◽  
Overall Response Rate ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Full Dose ◽  
Grade 3 ◽  
Positive Effect

Abstract Background: The activity of V in myeloma was first described in the 1970’s. Although Phase II data suggest that V demonstrates single agent activity, subsequent reports have questioned its role. Due to these conflicting results, we conducted a subanalysis investigating the effect of V dose in the phase II DVd-T regimen that we have previously reported (Agrawal et al ASH 2003). We evaluated the effects of V dose on progression free survival (PFS) and overall survival (OS) in newly diagnosed and relapsed/refractory patients treated with DVd-T. Patients and Methods: As previously reported, this Phase II study enrolled 102 patients with newly diagnosed or relapsed/refractory multiple myeloma with evidence of end organ damage. DVd-T was administered as previously reported. After best response, patients were maintained on prednisone 50mg every other day and the maximum tolerated dose of thalidomide until disease progression. For patients experiencing grade 1 neuropathy, V was reduced by 25%, and for grade 2, by 50%. Patients developing grade 3/4 neuropathy had V discontinued and thalidomide suspended until toxicity decreased by at least one grade. Univariate analyses were conducted to assess the effect of V dose reduction or elimination on PFS and OS. Multivariate analyses were performed to adjust for the impact of age, platelet count, stage, quality of response (CR or near CR versus SD or PR), and thalidomide dose. Results: Trial included 53 newly diagnosed and 49 relapsed/refractory patients. Median age was 62.9 years. 59% had stage 3 or 4 disease. 37% had abnormal cytogenetics. Median beta-2 microglobulin was 4.1. Overall response rate of 87% was seen in newly diagnosed patients (36% achieved CR; 13% near CR; 38% PR; 8% SD; 6% PD). In the relapsed/refractory patients, overall response rate of 87% was achieved (21% achieved CR; 26% near CR; 40% PR; 13% SD). Median follow up was 28.1 months. Median PFS for the newly diagnosed group was 28.2 months and 15.5 for the relapsed/refractory group. Median OS was 39.9 months for the relapsed/refractory group. After 50 months of follow-up for the newly diagnosed group, median OS has not been reached. In total, 464 cycles were administered, of which 225 were given with full dose V and 242 with reduced dose or eliminated V. Grade 3/4 neuropathy occurred in 22 patients. Univariate analysis revealed that reducing or eliminating V had a significant positive effect on PFS and OS (p = 0.0002 and 0.02 respectively). Multivariate analysis adjusting for age at start of study, platelet count, stage, quality of response [CR or near CR versus SD or PR], and thalidomide dose, similarly found that reducing or eliminating the dose of V had a significant positive effect (p = 0.0121) on PFS. However, multivariate analysis did not reveal the same effect on OS (p = 0.11). Conclusions: This subanalysis suggests that the use of full dose V in the DVd-T regimen may have a negative effect on PFS. The exact mechanism by which V affects PFS is not clear. Studies are now on-going investigating this regimen without V. Figure Figure

RTOG 0131: Phase II trial of pre-irradiation and concurrent temozolomide in patients with newly diagnosed anaplastic oligodendrogliomas and mixed anaplastic oligodendrogliomas: Relationship between 1p/19q status and progression-free survival

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1517-1517 ◽  
Author(s):  
M. A. Vogelbaum ◽  
B. Berkey ◽  
D. Peereboom ◽  
C. Giannini ◽  
R. Jenkins ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Median Time ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Chromosome 8 ◽  
Newly Diagnosed ◽  
Time To Progression ◽  
Durable Response ◽  
Free Survival

1517 Background: In a previous report, we showed in patients with newly diagnosed anaplastic oligodendrogliomas (AOs) and mixed anaplastic oligoastrocytomas (MAOs) that temozolomide (TMZ) can be given concurrently with radiation therapy (RT) with acceptable toxicity. We have now evaluated the efficacy of this regimen and correlated durability of response with tumor 1p/19q genotype. Methods: A phase II study was performed to evaluate the use of pre-RT TMZ followed by concurrent RT and TMZ in patients with newly diagnosed AO or MAO. The primary endpoint was to determine the pre-RT TMZ six-month progression rate, and secondary endpoints included progression-free survival and overall survival. Results: 40 eligible patients were entered into the trial. Thirty-two patients completed 6 months of pre-RT TMZ and concurrent RT and TMZ. Of the remaining eight patients, 4 withdrew due to toxicity and 4 other patients withdrew from study without evidence of toxicity or pre-RT progression. 1p/19q data are available in 37 cases; 23 tumors had loss of heterozygosity (LOH) of both 1p and 19q (double-deleted) while 14 tumors had LOH of either 1p or 19q (n = 3), or no LOH (n = 11). To date, 11 patients have experienced tumor progression; 1p/19q data are available for 10 of these cases (2 are double-deleted (2/23 = 9%), 8 have at least one intact chromosome (8/14 = 57%). Kaplan-Meier analysis demonstrates that progression free survival is significantly better for the double-deleted group (median time to progression not reached) than for the intact group (median time to progression = 15.2 months, p = 0.001). Overall survival is 98% (39/40) with a median follow-up of 17.5 months (2.8 - 31.1 months). Conclusions: LOH of both 1p and 19q is strongly correlated with a durable response of AO and MAO to a combined regimen of chemotherapy and radiation therapy. Tumors that are intact at 1p and/or 19q progress early despite an aggressive therapeutic regimen. These results suggest that future clinical trials should be prospectively stratified by tumor 1p/19q genotype. [Table: see text]

Phase II study of bevacizumab in combination with docetaxel and carboplatin in patients with metastatic non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18098-18098 ◽  
Author(s):  
W. N. William ◽  
M. S. Kies ◽  
F. V. Fossella ◽  
G. Gladish ◽  
J. V. Heymach ◽  
...  
Keyword(s):  
Phase Ii ◽  
Progression Free Survival ◽  
Stage Iiib ◽  
Limited Data ◽  
Eligibility Criteria ◽  
Free Survival ◽  
Peritoneal Perforation ◽  
Cardiac Condition ◽  
History Of ◽  
Grade 3

18098 Background: The combination of bevacizumab, paclitaxel and carboplatin has been recently shown to increase response rates and survival in patients (pts) with untreated, metastatic, non-squamous, NSCLC and is currently FDA-approved for this indication. However, there are limited data on the safety and efficacy of bevacizumab in combination with other widely used chemotherapy doublets for NSCLC. This is a single-arm, open-labeled, phase II trial of bevacizumab, docetaxel and carboplatin for pts with NSCLC. Methods: Eligibility criteria included chemotherapy-naïve stage IIIB or IV incurable NSCLC of non-squamous cell histology, PS 0–1, no brain metastases, no history of hemoptysis, no cavitation, stable cardiac condition and no full dose anticoagulation. Treatment consisted of docetaxel 75 mg/m2, carboplatin AUC 6, and bevacizumab 15 mg/kg IV on day 1 every 3 weeks for up to 6 cycles followed by bevacizumab 15 mg/kg alone every 3 weeks until progression. The primary endpoint was progression-free survival. Results: 20 pts (12 females) have been enrolled with a planned sample size of 50 pts. Baseline characteristics were: median age 66 years old (37–77), PS 0 (6 pts) or 1 (14 pts), stage IIIB (1 pt) or IV (19 pts). 19 pts are evaluable for response and toxicity at this time. Severe adverse events (SAEs) included: 4 pts with neutropenia (2 febrile neutropenias), mild hemoptysis in 2 pts (treated with radiotherapy), 1 pt with peritoneal perforation (who had a history of diverticula), 1 pt with pulmonary embolism, and 1 pt with grade 3 hypertension. Partial responses by RECIST have been observed in 14 pts (74%, 13 confirmed), and stable disease in 5 pts (26%, 4 confirmed). Disease control rate (PR+SD) was 100% after 4 cycles of therapy. 9/20 pts are off treatment (3 progressions, 5 SAEs, 1 maximal benefit). Progression-free survival will be reported at the completion of the trial. Conclusions: The combination of bevacizumab, docetaxel and carboplatin appears to be efficacious and tolerable for the first-line treatment of metastatic NSCLC. No significant financial relationships to disclose.

Phase II trial of bolus 5-FU/l-LV regimen as salvage line chemotherapy for oral fluorouracil resistant unresectable gastric cancer (HGCSG1502).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS177-TPS177
Author(s):  
Tetsuhito Muranaka ◽  
Satoshi Yuki ◽  
Kentaro Sawada ◽  
Yasuyuki Kawamoto ◽  
Hiroshi Nakatsumi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Continuous Infusion ◽  
Phase Ii ◽  
Bolus Injection ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Dependent Manner ◽  
Eligibility Criteria ◽  
Concentration Dependent Manner ◽  
Free Survival

TPS177 Background: S-1, oral fluorouracil agent compounding tegafur, 5-chloro-2, 4-dihydropyrimidine, and potassium oxonate for gastric cancer showed non-inferiority relative to a continuous infusion of fluorouracil in JCOG9912 trial. Similarly, in ISO-5FU10 trial, S-1 revealed non-inferiority effect compared with the treatment with bolus 5-FU/l-LV treatment. It is known that there is a different mechanism of anti-cancer effect between continuous 5-FU and bolus injection of 5-FU. Continuous infusion of 5-FU and oral fluorouracil inhibit DNA synthesis, however, bolus injection of 5-FU causes dysfunction of RNA in a concentration-dependent manner. So we considered bolus 5-FU/l-LV treatment might be useful for oral fluorouracil resistant patients with gastric cancer. Methods: This is a multi-centered single-arm prospective phase II study in Japanese patients with oral fluorouracil resistant gastric cancer. The key eligibility criteria are as follows: 1) Pathologically diagnosed gastric adenocarcinoma: 2) Unresectable advanced, metastatic, or recurrent disease; 3) resistance of S-1 or capecitabine; 4) resistance or intolerance of cisplatin or oxaliplatin, paclitaxel or docetaxel, and ramucirumab; 5) 20 years of age or older; 6) ECOG PS of 0, 1 or 2. Bolus 5-FU/l-LV regimen consists of l-LV 250mg/m2/2h iv and 5-FU 600mg/m2 iv bolus given intravenously once weekly followed by 2-week rest period, within a 8-week cycle. The primary endpoint is progression free survival rate after 1cycle administration. And the secondary endpoints are response rate, disease control rate, overall survival, progression free survival, time to treatment failure, adverse events, dose intensity and QOL by EORTC QLQ-C30. This study is recruiting in Hokkaido Gastrointestinal Cancer Study Group and registered as UMIN000018882. Clinical trial information: UMIN000018882.

Dendritic cell vaccine (DCVAC) combined with chemotherapy (CMT) in patients with newly diagnosed epithelial ovarian carcinoma (EOC) after primary debulking surgery (PDS): Biomarker exploratory analysis of a phase 2, open-label, randomized, multicenter trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5521-5521
Author(s):  
Lukas Rob ◽  
David Cibula ◽  
Pawel Knapp ◽  
Peter Mallmann ◽  
Jaroslav Klat ◽  
...  
Keyword(s):  
T Cell ◽  
Clinical Outcomes ◽  
Tumor Antigens ◽  
Progression Free Survival ◽  
Cd8 T Cell ◽  
Cell Vaccine ◽  
Newly Diagnosed ◽  
Open Label ◽  
Eligibility Criteria ◽  
Cell Counts

5521 Background: Most patients with EOC relapse despite PDS and CMT. Autologous DCVAC can present tumor antigens to elicit a durable immune response. We hypothesized that adding DCVAC to CMT stimulates antitumor immunity and improves clinical outcomes. Methods: Key eligibility criteria were FIGO stage III EOC (serous, endometrioid, or mucinous), post-PDS with < 1 cm maximal residuum, no prior systemic therapy, and ECOG 0-2. In part 1, patients were randomized up to 6 weeks after PDS, 1:1:1, into arm A (A; DCVAC concomitant with CMT), arm B (B; DCVAC sequential after CMT), and arm C (C; CMT). Patients were stratified by tumor residuum (0 or < 1 cm). CMT consisted of 6 cycles of carboplatin (AUC 5-7) and paclitaxel (175 mg/m2). Patients in A and B received up to 10 doses of DCVAC (1×107 DCs/dose). The primary endpoint was radiologically assessed progression-free survival (PFS). The key secondary endpoint was overall survival (OS). Results presented refer to a protocol-defined modified intention-to-treat population (mITT) including patients who received ≥1 CMT dose in C or ≥1 DCVAC dose in A and B. Results: Between November 2013 and March 2016, 99 patients were randomized. At the final analysis, the mITT included 31 patients in A, 29 patients in B, and 30 patients in C. Key baseline characteristics and DCVAC exposure were comparable across treatment arms. Median PFS was 20.3 months in A, not reached in B, and 21.4 months in C, with corresponding HRs (95% CI) compared to C of 0.98 (0.48-2.00) in A and 0.39 (0.16-0.96) in B. The PFS benefit in B was statistically significant (p = 0.034) This was supported by a non-significant trend in OS in A and B. Median OS was not reached in any arm at the time of median follow-up of 66 months (34% of events). Patients with low CD8+ T-cell counts (CD8Lo) in tumor samples in A and B had significantly improved clinical outcomes compared to patients in C with CD8Lo: median PFS gain of 6 months (19 vs 13 months) and a more robust OS gain (median not reached vs 31 months), with minimal difference between A and B. This effect could not be attributed to statistical differences in high CD8+ T-cell counts (CD8Hi) density patients. These findings indicated the best clinical outcome in DCVAC patients with immunologically “cold” tumors in both DCVAC arms. DCVAC showed a good safety profile with only 8 DCVAC-related adverse events (Grade 1-2). Conclusions: DCVAC improved PFS and OS outcomes in patients with newly diagnosed EOC, predominantly in patients with immunologically “cold” tumors, thus representing a promising treatment option in this patient population. Clinical trial information: NCT02107937.

scholarly journals Audencel Immunotherapy Based on Dendritic Cells Has No Effect on Overall and Progression-Free Survival in Newly Diagnosed Glioblastoma: A Phase II Randomized Trial

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 372 ◽  
Author(s):  
Johanna Buchroithner ◽  
Friedrich Erhart ◽  
Josef Pichler ◽  
Georg Widhalm ◽  
Matthias Preusser ◽  
...  
Keyword(s):  
Overall Survival ◽  
Dendritic Cells ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Severe Toxicity ◽  
Newly Diagnosed ◽  
Skin Reactions ◽  
Local Skin ◽  
Free Survival ◽  
Newly Diagnosed Glioblastoma

Dendritic cells (DCs) are antigen-presenting cells that are capable of priming anti-tumor immune responses, thus serving as attractive tools to generate tumor vaccines. In this multicentric randomized open-label phase II study, we investigated the efficacy of vaccination with tumor lysate-charged autologous DCs (Audencel) in newly diagnosed glioblastoma multiforme (GBM). Patients aged 18 to 70 years with histologically proven primary GBM and resection of at least 70% were randomized 1:1 to standard of care (SOC) or SOC plus vaccination (weekly intranodal application in weeks seven to 10, followed by monthly intervals). The primary endpoint was progression-free survival at 12 months. Secondary endpoints were overall survival, safety, and toxicity. Seventy-six adult patients were analyzed in this study. Vaccinations were given for seven (3–20) months on average. No severe toxicity was attributable to vaccination. Seven patients showed flu-like symptoms, and six patients developed local skin reactions. Progression-free survival at 12 months did not differ significantly between the control and vaccine groups (28.4% versus 24.5%, p = 0.9975). Median overall survival was similar with 18.3 months (vaccine: 564 days, 95% CI: 436–671 versus control: 568 days, 95% CI: 349–680; p = 0.89, harzard ratio (HR) 0.99). Hence, in this trial, the clinical outcomes of patients with primary GBM could not be improved by the addition of Audencel to SOC.

Phase II study alternating mFOLFOX 6 and FOLFIRI (FIREFOX) plus bevacizumab (bev) regimen in first-line treatment of advanced colorectal cancer in Japanese patients (KSCC 0801).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 602-602
Author(s):  
Yutaka Ogata ◽  
Yoshito Akagi ◽  
Yoshihiro Kakeji ◽  
Yasunori Emi ◽  
Eiji Oki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
First Line ◽  
Eligibility Criteria ◽  
Free Survival ◽  
Ecog Ps

602 Background: The Kyushu Study group of Clinical Cancer conducted a phase II study that evaluated the FIREFOX regimen. (KSCC0701, Akagi et al, J Clin Oncol 28:15s, 2010). This study demonstrated the efficacy and mild neurotoxicity of this regimen. The present study evaluated the efficacy and safety of the FIREFOX plus bevacizumab (bev). Methods: Eligibility criteria included histologically confirmed advanced colorectal cancer, ECOG PS 0-2 and adequate bone marrow, renal and hepatic function. Patients (pts) received an alternating regimen of 4 cycles of mFOLFOX-6 plus bev (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, bev 5 mg/kg d1 followed by 400 mg/m2 bolus 5-FU and a 46-hr 2,400 mg/m2 5-FU infusion every 2 weeks) followed by 4 cycles of FOLFIRI plus bev (oxaliplatin replaced with irinotecan 150 mg/m2 d1). This schedule was repeated until unacceptable toxicity or disease progression occurred. The primary endpoint is progression-free survival. (UMIN000001312) Results: Of the 52 pts enrolled from May 2008 to July 2009. Two of the patients did not fulfill the eligibility criteria. M/F, 30/20; median age, 59.5 years (range 37 - 75); ECOG PS 0/1/2, 46/4/0. The median number of administration cycles was 14 (range, 2 - 44). Response rate (RECIST criteria) for CR, PR, SD, PD and NE were 2 (4%), 28 (56%), 14 (28%), 4 (8%) and 2 (4%), respectively. An overall response rate was 60% (95% CI: 45 - 74%). Median progression-free survival was14.2 M (95% CI: 10.6 M-16.3 M) and median overall survival was 27.5 M (95% CI; 22.4 M – not determined). The 2-year survival rate was 56.8%. Of the 52 pts evaluated for toxicity. The most common grade 3-4 adverse events were leukopenia (7.7%), neutropenia (32.7%), anemia (1.9%), fatigue (9.6%), anorexia (13.5%), stomatitis (3.8%), neurotoxicity (3.8%), hypertension (1.9%), diarrhea (7.7%), febrile neutropenia (3.8%), nausea (9.6%), vomiting (5.8%), hypersensitivity (3.8%), and thromboembolism (1.9%). Conclusions: The results of this phase II study show that the FIREFOX plus bev regimen is effective and well tolerated in the first-line treatment of advanced colorectal cancer. The low rate of neurotoxicity is also promising.

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.

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