Efficacy and safety results from neopembrov study, a randomized phase II trial of neoadjuvant chemotherapy (CT) with or without pembrolizumab (P) followed by interval debulking surgery and standard systemic therapy ± P for advanced high-grade serous carcinoma (HGSC): A GINECO study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5500-5500
Author(s):  
Isabelle Laure Ray-Coquard ◽  
Aude Marie Savoye ◽  
Marie-ange Mouret-Reynier ◽  
Sylvie Chabaud ◽  
Olfa Derbel ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Figo Stage ◽  
Complete Resection ◽  
Serous Carcinoma ◽  
Debulking Surgery ◽  
Randomized Phase Ii ◽  
Interval Debulking Surgery ◽  
Clinical Trial Information

5500 Background: To investigate whether adding Pembrolizumab (P) to neoadjuvant carboplatin-paclitaxel chemotherapy (CP) may increase the optimal debulking rate, assessed by Complete Resection Rate (CRR) after Interval Debulking Surgery (IDS) in patients (pts) with initially unresectable International Federation of Gynecology and Obstetrics (FIGO) stage IIIC/IV ovarian, tubal or peritoneal HGSC. Methods: Multicenter, open-label, non-comparative randomized phase II trial. Pts were randomized (2:1) to receive 4 cycles of CP ± P before IDS. After IDS, all patients received post-operative chemotherapy (2 to 4 cycles) and optional bevacizumab for 15 months in total ± P as maintenance therapy for up to 2 years. Randomization was stratified on center, FIGO stage, Bev planned after IDS and disease volume (<5cm/>5cm). Primary endpoint was the centrally reviewed CRR at IDS. 60 pts were planned in the CP+P arm (A'Hern's single-stage design P0=50%, P1=70%). Safety (particularly due to P addition), surgical morbidity, ORR, PFS and OS were secondary endpoints. Results: 91 pts were randomized from 02/18 to 04/19 with a median Peritoneal Cancer Index at 24 (range 7-39). 80 pts (88%) received Bev in combination with CP followed by bev ± P in maintenance. In the CP+P group (n=61), 58 (95%) pts had IDS and 78% achieved complete resection. The CRR in this group was 74%, statistically superior to the pre-defined hypothesis. In the CP group, CRR was 70% (29/30 pts underwent IDS). Complete resection after strictly 4 cycles of CP±P was obtained for 41 pts (71%) and 17 (58%) pts in CP+P and CP group, respectively (sensitivity analysis). For CP+P group, numerically higher ORRs were observed before IDS compared to CP group (76% vs 61%). Grade ≥3 adverse events (AE) occurred in 75% of the CP+P group and 67% in the CP group: mainly blood and lymphatic, gastrointestinal and vascular disorders. Postoperative AE (mainly infectious, vascular and gastrointestinal) occurred in 20% and 13% of the pts in CP+P and CP arm, respectively. No difference in the number of fatal events between the two arms: 2 in the experimental arm vs 1 in the control arm. Progression free survival rate at 18 months was 61% (95CI% [47-73]) and 57% (95CI% [37-72]) in CP+P and CP arm, respectively. Conclusions: P may be safely added to preoperative treatment in pts deemed non-optimally resectable. The primary objective was met with an improved CRR on CP+P arm. The CRR in the control group was higher than expected. Survival data and translational research including PDL1 status are ongoing to better define P as treatment option in this setting. Clinical trial information: 2016-004-163-39. Clinical trial information: NCT03275506.

Efficacy and safety results from GEICO 1205, a randomized phase II trial of neoadjuvant chemotherapy with or without bevacizumab for advanced epithelial ovarian cancer

2019 ◽  
Vol 29 (6) ◽  
pp. 1050-1056 ◽  
Author(s):  
Yolanda Garcia Garcia ◽  
Ana de Juan Ferré ◽  
Cesar Mendiola ◽  
Maria-Pilar Barretina-Ginesta ◽  
Lydia Gaba Garcia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Adverse Events ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Debulking Surgery ◽  
Randomized Phase Ii ◽  
Interval Debulking Surgery ◽  
Grade 3 ◽  
Macroscopic Response

BackgroundBevacizumab is an approved treatment after primary debulking surgery for ovarian cancer. However, there is limited information on bevacizumab added to neoadjuvant chemotherapy before interval debulking surgery.ObjectiveTo evaluate neoadjuvant bevacizumab in a randomized phase II trial.MethodsPatients with newly diagnosed stage III/IV high-grade serous/endometrioid ovarian cancer were randomized to receive four cycles of neoadjuvant chemotherapy with or without ≥3 cycles of bevacizumab 15 mg/kg every 3 weeks. After interval debulking surgery, all patients received post-operative chemotherapy (three cycles) and bevacizumab for 15 months. The primary end point was complete macroscopic response rate at interval debulking surgery.ResultsOf 68 patients randomized, 64 completed four neoadjuvant cycles; 22 of 33 (67%) in the chemotherapy-alone arm and 31 of 35 (89%) in the bevacizumab arm (p=0.029) underwent surgery. The complete macroscopic response rate did not differ between treatment arms in either the intention-to-treat population of 68 patients (6.1% vs 5.7%, respectively; p=0.25) or the 55 patients who underwent surgery (8.3% vs 6.5%; p=1.00). There was no difference in complete cytoreduction rate or progression-free survival between the treatment arms. During neoadjuvant therapy, grade ≥3 adverse events were more common with chemotherapy alone than with bevacizumab (61% vs 29%, respectively; p=0.008). Intestinal (sub)occlusion, fatigue/asthenia, abdominal infection, and thrombocytopenia were less frequent with bevacizumab. The incidence of grade ≥3 adverse events was 9% in the control arm versus 16% in the experimental arm in the month after surgery.ConclusionsAdding three to four pre-operative cycles of bevacizumab to neoadjuvant chemotherapy for unresectable disease did not improve the complete macroscopic response rate or surgical outcome, but improved surgical operability without increasing toxicity. These results support the early integration of bevacizumab in carefully selected high-risk patients requiring neoadjuvant chemotherapy for initially unresectable ovarian cancer.

A randomized, double-blinded, placebo-controlled multicenter phase II trial of adjuvant immunotherapy with tecemotide (L-BLP25) after R0/R1 hepatic colorectal cancer metastasectomy (LICC): Final results.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 480-480
Author(s):  
Carl Christoph Schimanski ◽  
Stefan Kasper ◽  
Susanna Hegewisch-Becker ◽  
Jan Schroeder ◽  
Friedrich Overkamp ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Cox Regression ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
High Recurrence Rate ◽  
Muc1 Expression ◽  
Double Blinded ◽  
Clinical Trial Information

480 Background: Hepatic metastasectomy is the only potential curative treatment option for stage IV colorectal cancer (CRC) limited to liver metastases (LM). After R0 resection of LM the high recurrence rate remains a major challenge. L-BLP25 is an antigen-specific cancer vaccine targeting mucin 1 (MUC1). The LICC trial aimed to improve survival outcome in mCRC patients (pts) after R0/R1 LM resection. Methods: This LICC trial, a binational, multicenter, double-blinded, placebo controlled phase II trial, included pts with stage IV LM limited CRC after resection of primary tumor and LM (R0/R1) within the last 8 weeks, ECOG 0/1 and adequate organ function. Pts were 2:1 randomized to receive L-BLP25 or placebo. L-BLP25 930 µg was administered as 8 weekly subcutaneous doses followed by 6 week maintenance intervals until recurrence or a maximum of 2 years. Cyclophosphamide 300 mg/m2 (CP) or matching saline (NS) was given intravenously 3 days prior to first L-BLP25/placebo. Co-primary endpoints were recurrence-free survival (RFS) and 3-year overall survival (OS), secondary endpoints were RFS and OS in subgroups with different MUC1 expression and safety. Differences in RFS and OS were analyzed with exploratory log-rank tests on the intention-to-treat population. Results: Of 121 pts enrolled between Oct 2011 and Dec 2014, 79 pts received L-BLP25+CP, 42 placebo+NS. Baseline characteristics were well balanced. Median age was 60 years. Median RFS was 6.1 (90% CI: 5.8-8.8) vs. 11.4 months (90% CI: 5.0-20.3) and estimated 3-year OS rate 69.1% vs. 79.1% for L-BLP25 and placebo, respectively. Two-factorial Cox regression models showed no impact of MUC1 expression or treatment on RFS or OS. The most common L-BLP25-related grade 3/4 adverse events were diarrhea, anemia and back pain. There was one death in the L-BLP25 arm due to Merkel cell carcinoma assessed by the investigator as being potentially related to vaccination. Conclusions: The LICC trial failed to meet its primary endpoint of significantly improving RFS and OS with L-BLP25. MUC1 expression was not associated with outcome. Clinical trial information: NCT01462513 . Clinical trial information: NCT01462513.

Incidence and risk factor analysis of the postoperative delirium after gastrointestinal surgery: An exploratory analysis of a prospective, randomized phase II trial.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 30-30 ◽  
Author(s):  
Shinya Amano ◽  
Toru Aoyama ◽  
Mariko Kamiya ◽  
Junya Morita ◽  
Yukio Maesawa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Trial ◽  
Risk Factor ◽  
Phase Ii ◽  
Odds Ratio ◽  
Postoperative Delirium ◽  
Phase Ii Trial ◽  
Mmse Score ◽  
Gastrointestinal Surgery ◽  
Randomized Phase Ii

30 Background: The postoperative complications, delirium are a particularly common morbidity after gastrointestinal surgery. Postoperative delirium makes patient management much more difficult, increases costs, and causes severe discomfort to the patient. The aim of this study was to evaluate the incidence of the postoperative delirium and a predictor for postoperative delirium using phase II clinical trial data. Methods: We analyzed the cases that were enrolled to randomized clinical trials of the efficacy and safety of TJ-54 (Yokukansan; a traditional Japanese medicine [Kampo]) for the prevention and/or treatment of postoperative delirium in a randomized phase II trial of patients receiving surgery for gastrointestinal and lung malignancies (UMIN000005423). The American Psychiatric Association’s the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) was used to assess. A uni- and multivariate logistic regression analyses was performed to identify risk factors for morbidity. Results: Between October 2009 and July 2011, a total of 186 patients were registered to the Yokukansan trial. Among them, 167 patients received surgery for gastrointestinal malignancy and were eligible for the present study. The incidence of postoperative delirium was 9.0% (15 patients) and postoperative delirium was the most common postoperative complication in the study. Risk factors for postoperative delirium were analyzed by uni- and multi-variate analyses using clinical factors determined before the enrollment of the study. Among these, high patients’ age ( > 80 years) and low MMSE score ( < 27) were identified as significant independent risk factor for postoperative delirium (Odds ratio: 3.90, 95% CI; 1.25-12.16, p = 0.013 and Odds ratio: 0.24, 95% CI; 0.08-0.73, p = 0.013). Conclusions: The major of the findings were that high patients’ age (≥ 80 years) and low MMSE score ( < 27) were significant independent risk factors for predicting postoperative delirium. Careful attention for postoperative delirium is required in patients with high patients’ age and MMSE score when surgeons perform surgery for gastrointestinal malignancies. Clinical trial information: 000005423.

Assessing safety and activity of cabozantinib combined with lanreotide in gastroenteropancreatic (GEP) and thoracic neuroendocrine tumors (NETs): The phase II LOLA trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4167-TPS4167
Author(s):  
Francesca Corti ◽  
Vito Amoroso ◽  
Davide Campana ◽  
Maria Pia Brizzi ◽  
Francesco Panzuto ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Synergistic Effects ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Unknown Origin ◽  
Drop Out ◽  
Therapeutic Options ◽  
Clinical Trial Information

TPS4167 Background: Well-differentiated (WD) NETs are a group of rare neoplasms with limited therapeutic options. New combinations of somatostatin analogs (SSAs) and investigational drugs are warranted to improve clinical outcomes. Cabozantinib (CAB) is an orally administered inhibitor of multiple tyrosine kinases, including c-MET and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), with a pivotal role in NET pathogenesis. The biological rationale of the synergistic effects of CAB plus SSAs lies in the concomitant modulation of the RAS/MAPK and PI3K/Akt/mTOR pathways both at the level of cancer cells and tumor stroma, leading to enhanced anti-proliferative and anti-angiogenic effects. CAB exhibited encouraging activity in a recent phase II trial of patients with progressive carcinoids and pancreatic (p)NETs (Chan JA et al. JCO 2017; 35:4_suppl, 228-228). The LOLA trial is the first prospective phase II study aiming to assess the safety and activity of CAB in combination with lanreotide (LAN) in WD NETs of GEP, thoracic and of unknown origin. Clinical trial information: NCT04427787. Methods: This is a multicenter, open-label, double-cohort, non comparative, non-randomized, three-stage phase II trial. Eligible patients have to meet the following inclusion criteria: diagnosis of advanced or metastatic, progressive, non-functioning WD thoracic NETs, GEP-NETs or NETs of unknown origin with Ki67 ≥10%; positive 68Ga-PET uptake or somatostatin receptor 2 immunohistochemical (IHC) stain; maximum 1 prior systemic regimen for metastatic disease. Two cohorts will be considered: pNETs and carcinoids. In the stage I, the primary objective is to find the optimal dose of CAB in combination with LAN and to evaluate the safety of the combination (defined as the percentage of patients experiencing grade 3-5 toxicities according to NCI-CTCAE v5.0). Starting dose of CAB is 60 mg/day continuously, plus LAN 120 mg every 28 days. In stage II and III, co-primary endpoints are safety and overall response rate (ORR) according to RECIST v1.1. The useful antitumor activity to be detected is fixed in ORR > 20%. Secondary endpoints are progression-free survival and overall survival. Exploratory objectives include the assessment of IHC expression of c-MET, AXL and VEGFR2, with the aim to identify predictive or prognostic tissue biomarkers. Enrolment started in July 2020, with an expected trial duration of 42 months comprehensive of accrual, treatment and follow-up. Considering a drop out rate of 5%, the maximum number of enrolled patients will be 69. Supported by a solid rationale, the trial has the potential to generate milestone data about the synergistic effects of CAB plus LAN in a group of NET patients with relatively aggressive disease and limited therapeutic options, for whom optimal treatment sequencing is not yet defined. Clinical trial information: NCT04427787.

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