Safety of perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma: An interim safety analysis of the DANTE, a randomized, open-label phase II trial of the German Gastric Group at the AIO and the SAKK.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 398-398
Author(s):  
Salah-Eddin Al-Batran ◽  
Sylvie Lorenzen ◽  
Michael Schenk ◽  
Peter C. Thuss-Patience ◽  
Eray Goekkurt ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Safety Analysis ◽  
Open Label ◽  
Serious Adverse Events ◽  
Open Label Phase

398 Background: The DANTE study evaluates atezolizumab in the perioperative treatment of locally advanced, potentially resectable gastric or GEJ adenocarcinoma in combination with perioperative FLOT. Here, we report the protocol-defined interim safety analysis. Methods: DANTE is a large, multinational, prospective, multicenter, randomized, investigator-initiated, open label phase II trial. Patients (pts) with locally advanced, potentially resectable adenocarcinoma of the stomach and GEJ (≥cT2 and/or N-positive) without distant metastases are enrolled. Pts are randomized 1:1 to 4 pre-operative 2-week cycles (8 weeks) of FLOT followed by surgery and 4 additional cycles of FLOT plus atezolizumab at 840 mg every 2 weeks, followed by a total of 8 additional cycles of atezolizumab at 1200 mg every 3 weeks as monotherapy (arm A) or FLOT alone (arm B). Primary endpoint is time to disease progression or relapse after surgery (PFS/DFS). Results: Recruitment started in Sept 2018; by September 2019, a total of 122 pts have been randomized. This analysis is based on the first 40 pts (20 pts in each arm). The pts had a median age of 62 y and 75% of pts had an ECOG PS of 0 in both arms. The cohort was well balanced in terms of tumor location and clinical stage. 90% of pts enrolled completed all pre-operative cycles in each arm. Total number of adverse events with relation to study treatment was 154 in arm A and 148 in arm B. Total number of serious adverse events (SAE; related or not) was 16 in Arm A and 14 in arm B. 20% of pts in each arm had an SAE due to perioperative morbidity. No surgical mortality was observed. 18 and 19 pts proceeded to operation in arms A and B, respectively. Premature treatment discontinuation occurred in 2 pts in each arm: disease progression (1) and deterioration of general health condition (1) in arm A; and pts’ wish (1) and death (1) in arm B. Median hospitalization time was 15 days in arm A and 16 days in arm B. Conclusions: perioperative atezolizumab plus FLOT is feasible and safe. The study continued recruitment. Clinical trial information: NCT03421288.

Interim safety analysis of the DANTE trial: Perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma—A randomized, open-label phase II trial of the German Gastric Group at the AIO and SAKK.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4549-4549
Author(s):  
Nils Homann ◽  
Sylvie Lorenzen ◽  
Michael Schenk ◽  
Peter C. Thuss-Patience ◽  
Eray Goekkurt ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Safety Analysis ◽  
Open Label ◽  
Serious Adverse Events ◽  
Open Label Phase

4549 Background: The DANTE study evaluates atezolizumab in the perioperative treatment of locally advanced, potentially resectable gastric or GEJ adenocarcinoma in combination with perioperative FLOT. Here, we report the protocol-defined interim safety analysis. Methods: DANTE is a multinational, prospective, multicenter, randomized, investigator-initiated, open label phase II trial. Patients (pts) with locally advanced, potentially resectable adenocarcinoma of the stomach and GEJ (≥cT2 and/or N-positive) without distant metastases are enrolled. Pts are randomized 1:1 to 4 pre-operative 2-week cycles of FLOT followed by surgery and 4 additional cycles of FLOT plus atezolizumab at 840 mg every 2 weeks, followed by a total of 8 additional cycles of atezolizumab at 1200 mg every 3 weeks as monotherapy (arm A) or FLOT alone (arm B). Primary endpoint is time to disease progression or relapse after surgery (PFS/DFS). Results: Recruitment started in Sep 2018; by Feb 2020, a total of 175 pts have been randomized. This analysis is based on the first 40 pts (20 pts in each arm). The pts had a median age of 62 y and 75% of pts had an ECOG PS of 0 in both arms. The cohort was well balanced in terms of tumor location and clinical stage. 5% of the 40 patients (overall 7.4% of 175 pts enrolled) showed microsatellite instability. 90% of pts enrolled completed all pre-operative cycles in each arm. Total number of adverse events with relation to study treatment was 154 in arm A and 148 in arm B. Total number of serious adverse events (SAE; related or not) was 16 in Arm A and 14 in arm B. 20% of pts in each arm had an SAE due to perioperative morbidity. No surgical mortality was observed. 18 and 19 pts proceeded to operation in arms A and B, respectively. Premature treatment discontinuation occurred in 2 pts in each arm: disease progression (1) and deterioration of general health condition (1) in arm A; and pts’ wish (1) and death (1) in arm B. Median hospitalization time was 15 days in arm A and 16 days in arm B. Conclusions: Perioperative atezolizumab plus FLOT is feasible and safe. The study continues recruitment. Clinical trial information: NCT03421288 .

Perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma: DANTE, a randomized, open-label phase II trial of the German Gastric Group of the AIO and the SAKK.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4142-TPS4142
Author(s):  
Salah-Eddin Al-Batran ◽  
Claudia Pauligk ◽  
Ralf Hofheinz ◽  
Sylvie Lorenzen ◽  
Andreas Wicki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Rank Test ◽  
R0 Resection ◽  
Open Label ◽  
Significance Level ◽  
Esophagogastric Cancer ◽  
Open Label Phase

TPS4142 Background: Perioperative FLOT chemotherapy has become a standard of care for locally advanced, resectable gastric cancer and adenocarcinoma of the GEJ. However, patient outcomes are still unsatisfactory and 5-year survival in T3-4 or nodal positive disease is still around 50%. Targeting the PD-1/PD-L1 pathway has proven active in different cancers, including esophagogastric cancer, and was associated with response rates in the 10-15% range in unselected, heavily pre-treated gastric cancer patients. Atezolizumab is a PD-L1 inhibitor with established efficacy and tolerability profiles. This study evaluates atezolizumab in the perioperative treatment of locally advanced, potentially resectable gastric or GEJ adenocarcinoma in combination with FLOT. Methods: This is a large, multinational, prospective, multicenter, randomized, investigator-initiated, open label phase II trial. Patients with locally advanced, potentially resectable adenocarcinoma of the stomach and GEJ (≥cT2 and/or N-positive) without distant metastases are enrolled. Eligibility status is centrally evaluated. Patients are randomized 1:1 to 4 pre-operative 2-week cycles (8 weeks) of FLOT (Docetaxel 50 mg/m²; Oxaliplatin 85 mg/m²; Leucovorin 200 mg/m²; 5-FU 2600 mg/m²) followed by surgery and 4 additional cycles of FLOT plus atezolizumab at 840 mg every 2 weeks, followed by a total of 8 additional cycles of atezolizumab at 1200 mg every 3 weeks as monotherapy (arm A) or FLOT alone (arm B). Primary endpoint is time to disease progression or relapse after surgery (PFS/DFS) as assessed by the Kaplan-Meier-Method. The statistical design is based on a target HR of 0.68, a power of 0.8, and a significance level of p< 0.05 (1-sided log rank test). A total of 295 patients will be randomized. Main secondary endpoints are rates of centrally assessed pathological regression (rates of complete and nearly complete pathological regression), overall survival, R0 resection, and safety. Recruitment started in Sept 2018; by February 2019, a total of 27 patients have been randomized. Clinical trial information: NCT03421288.

Neoadjuvant treatment of locally advanced GIST: Results of APOLLON, a prospective, open label phase II study in KIT- or PDGFRA-positive tumors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10031-10031 ◽  
Author(s):  
Peter Hohenberger ◽  
Claus Langer ◽  
Clemens Martin Wendtner ◽  
Werner Hohenberger ◽  
Annette Pustowka ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Adjuvant Treatment ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Progression Rate ◽  
Open Label ◽  
Open Label Phase ◽  
Prospective Phase

10031 Background: Imatinib may significantly downstage the metastatic GIST. This prospective, phase II, open-label trial of neoadjuvant imatinib evaluated the overall tumor response and progression rate of disease in locally advanced, non-metastic patients. Methods: Inclusion criteria were: KIT (n=39) or PDFRA (n=6) positive GIST, proven by biopsy and IHC. Tumors had to be locally advanced, potentially resectable, M0. Patients received 400 mg of imatinib daily (KIT exon 9 mutations: twice daily) for 6 months, in the absence of disease progression or unacceptable toxicity. At two months 18F-FDG-PET examination was performed to assess response in paralle to CT imaging. Adjuvant treatment postoperatively was not part of the study protocol (CST1571-BDE43, NCT00112632). Median follow-up is 36 months in 39 patients. Results: From 7/2005 to 10/ 2009, 41 patients (16f, 25 m, mean age 54 yrs) were recruited to the trial with an average tumor size of 10.8 cm. One patient died from myocardial infarction 3 weeks after start of treatment, all other patients completed the protocol. In two patients dose reduction/interruption due to toxicity was required. 34/41 patients underwent resection of the tumor after a median of 200 d (range 57-394), while two patients had to be operated early due to disease progression. R0 resections were performed in 30/34 patients, two patients showed M1 disease at resection. Five patients showed developed progression postop., resulting in a PFS rate at 3 years of 85.2%. No patient has died so far from the disease. Conclusions: Neoadjuvant treatment with imatinib for six months is a safe treatment in patients with locally advanced disease. The extent of the operation can be significantly downsized after pretreatment. Despite the fact that no adjuvant treatment was foreseen, the progression-free rate at 3 years postoperatively is promising.

scholarly journals A randomized phase II trial of efficacy and safety of the immunotherapy ALECSAT as an adjunct to radiotherapy and temozolomide for newly diagnosed glioblastoma

2021 ◽  
Author(s):  
Katja Werlenius ◽  
Giuseppe Stragliotto ◽  
Michael Strandeus ◽  
Malin Blomstrand ◽  
Helena Carén ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Open Label ◽  
Serious Adverse Events ◽  
Significant Difference

Abstract Background There is an urgent need for effective treatments against glioblastoma (GBM). In this trial we investigated the efficacy and safety of an adoptive cell-based immunotherapy. Methods Patients with newly diagnosed GBM were recruited at four study sites in Sweden. The patients were randomized 1:2 to receive either radiotherapy (RT), 60 Gy/30 fractions, with concomitant and adjuvant temozolomide (TMZ) only, or RT and TMZ with addition of Autologous Lymphoid Effector Cells Specific Against Tumor (ALECSAT) in an open-label phase II trial. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were survival and safety of ALECSAT. Results Sixty-two patients were randomized to either RT and TMZ alone (n=22) or RT and TMZ with ALECSAT (n=40). Median age was 57 years (range 38-69), 95% of the patients were in good performance status (WHO 0-1). There was no significant difference between the study arms (SOC vs. ALECSAT + SOC) in PFS (7.9 vs. 7.8 months; HR 1.28; 95% CI 0.70, 2.36; P=0.42), or in median overall survival (OS) (18.3 vs. 19.2 months; HR 1.16, 95% CI 0.58, 2.31; P=0.67). The treatment groups were balanced in terms of serious adverse events (52.4% vs. 52.5%), but adverse events ≥ grade 3 were more common in the experimental arm (81.0% vs. 92.5%). Conclusion Addition of ALECSAT immunotherapy to standard treatment with radiochemotherapy was well tolerated but did not improve PFS or OS for patients with newly diagnosed GBM.

A phase I trial of a local delivery of siRNA against k-ras in combination with chemotherapy for locally advanced pancreatic adenocarcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4037-4037 ◽  
Author(s):  
Talia Golan ◽  
Ayala Hubert ◽  
Amotz Shemi ◽  
Amiel Segal ◽  
Alan Dancour ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Locally Advanced ◽  
Primary Study ◽  
Open Label ◽  
Serious Adverse Events ◽  
Line Setting

4037 Background:K-Ras mutation G12D is most prevalent in pancreatic adenocarcinoma (PDAC). siRNA against the K-RasG12D(siG12D) mutant had showed significant preclinical anti-tumor effects. siG12D LODER - miniature biodegradable polymeric matrix that encompasses anti-K-RasG12D siRNA drug, is placed with Endoscopic US biopsy and designed to continuously release the drug regionally over a period of 4 months. Methods: Open label phase I study of patients with locally advanced non-operable PDAC in the first-line setting. Patients were assigned to receive siG12D LODERs in dose escalation cohorts: 0.025mg, 0.75mg and 3.0mg. Gemcitabine 1000 mg/m2IV was given weekly, following siG12D LODER insertion. The RP2D (recommended phase II dose) was further examined in 3.0 mg dose cohort in combination with modified Folfirinox (Oxaliplatin 85mg/m2, Irinotecan 150mg/m2, Fluorouracil infusion 2,400mg/m2 46 hours, every 2 weeks). Follow up period was 8 weeks and survival follow up until death. Primary study objectives were to determine the dose-limiting toxicities (DLT) and maximum tolerated doses (MTD). Results:15 patients have been enrolled. 2 patients were omitted from study due to metastatic disease detected on day 1 post siG12D LODER implant imaging . Median age = 70 (range 52-85); male:female 8:7. Among 13 treated patients, the most frequent adverse events observed in the study were typically grade 1- 2 in severity; 4 patients experienced serious adverse events (SAE), one procedure related. No DLTs were observed. MTD was not reached. CT performed 8-10 weeks following the procedure showed stable disease in all patients. Reduction in tumor marker CA 19-9 was observed in 64% (7/11) of patients. The median survival of 13 patients was 16 months ( 8/13 patients still alive at analysis). Conclusions: The combination of siG12D LODER and chemotherapy is well tolerated. The combination has demonstrated promising efficacy in locally advanced PDAC with durable responses. Phamocodynamic endpoints are currently being examined in an expansion cohort in operable patients. A phase II randomized trial is planned in order to investigate efficacy of siG12D LODER in locally advanced non-operable PDAC. Clinical trial information: NCT01188785.

A Neoadjuvant, Randomized, Open-Label Phase II Trial of Afatinib Versus Trastuzumab Versus Lapatinib in Patients With Locally Advanced HER2-Positive Breast Cancer

2015 ◽  
Vol 15 (2) ◽  
pp. 101-109 ◽  
Author(s):  
Mothaffar F. Rimawi ◽  
Sabina B. Aleixo ◽  
Ashley Alarcon Rozas ◽  
João Nunes de Matos Neto ◽  
Maira Caleffi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Her2 Positive ◽  
Open Label ◽  
Her2 Positive Breast Cancer ◽  
Open Label Phase ◽  
Positive Breast Cancer
Sign in / Sign up

Export Citation Format

Share Document