scholarly journals ACTR-24. A RANDOMIZED PHASE II TRIAL OF VELIPARIB (V), RADIOTHERAPY (RT) AND TEMOZOLOMIDE (TMZ) IN PATIENTS (PTS) WITH UNMETHYLATED MGMT (uMGMT) GLIOBLASTOMA (GBM): THE VERTU STUDY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi18-vi18 ◽  
Author(s):  
Mustafa Khasraw ◽  
Kerrie Leanne McDonald ◽  
Mark Rosenthal ◽  
Zarnie Lwin ◽  
David Ashley ◽  
...  
Keyword(s):  
De Novo ◽  
Performance Status ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Randomized Phase Ii ◽  
Common Grade ◽  
Grade 3

Abstract BACKGROUND TMZ offers minimal benefit in pts with de novo uMGMT GBM. V is synergistic with RT and TMZ in uMGMT preclinical GBM models, safe when combined with either RT or TMZ clinically, but the triplet (V+RT+TMZ) is poorly tolerated. VERTU tested V in pts with uMGMT GBM. METHODS VERTU is a randomized Phase 2 trial comparing Standard Arm (Arm A), RT (60Gy/30 fractions) + TMZ (75mg/m2 daily) followed by TMZ (150–200mg/m2D 1–5) every 28 days for 6 cycles vs Experimental Arm (Arm B), RT (60Gy/30 fractions) + V (200mg PO BID) followed by TMZ (150–200mg/m2D 1–5) + V (40mg bid, D 1–7) every 28 days for 6 cycles in pts with de novo uMGMT GBM according to centralised testing. RESULTS 125 pts were randomized 1:2 (41:84). The 2 groups were matched for age, sex, performance status and extent of resection. Median follow-up was 25.8 months and 91 pts had died. The 6-month Progression-Free Survival (6mPFS) for Arms A and B were 34% (95% CI 20–48) and 46% (95% CI 36–57) respectively. The median PFS for Arms A and B were 4.2m (95% CI 2.5–6.0) and 5.7m (95% CI 4.1–6.6) respectively (HR = 0.80, 95%CI 0.55–1.18). 55% of pts in both arms experienced Grade 3/4 adverse events (AEs) with no significant differences in frequency or severity between the arms. Most common Grade 3/4 AEs were thrombocytopenia, seizures, hyperglycaemia and diarrhoea. CONCLUSION VERTU demonstrated that a novel treatment strategy for patients with de novo uMGMT GBM was feasible and tolerable. The observed 6mPFS and PFS were similar in both arms. Overall survival and other endpoints will be presented. Central MRI review, biomarker analyses, including DNA repair and methylation signature analyses are ongoing. (ANZCTR#ACTRN12615000407594).

NGR-hTNF and doxorubicin in relapsed ovarian cancer (OC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5059-5059
Author(s):  
Domenica Lorusso ◽  
Giovanni Scambia ◽  
Giulia Amadio ◽  
Alessia di Legge ◽  
Antonella Pietragalla ◽  
...  
Keyword(s):  
Median Duration ◽  
Human Tumor ◽  
Progression Free Survival ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Randomized Phase Ii ◽  
Common Grade ◽  
Grade 3 ◽  
Necrosis Factor

5059 Background: NGR-hTNF (asparagine-glycine-arginine human tumor necrosis factor) is able to promote antitumor immune responses and to improve the intratumoral doxorubicin (D) uptake by selectively damaging tumor vessels. Methods: OC patients (pts) with progressive disease (PD) after ≥ 1 platinum/taxane regimen and with a platinum free interval lower than 6 months (PFI <6) or ranging from 6 to 12 months (PFI 6-12) received NGR-hTNF (N) 0.8 µg/m2 and D 60 mg/m2 on day 1 every 3 weeks. Primary endpoint of this phase 2 trial was response rate by RECIST criteria with a target of ≥ 6/37 responding pts. Secondary aims were progression free survival (PFS) and overall survival (OS). Results: 37 pts (median age 57 years; PS 0/1 32/5; PFI < 6/6-12 25/12; prior regimens 1-5) were enrolled. Median baseline peripheral blood lymphocyte count (PBLC) was 1.6/mL (interquartile range 1.2-2.1). In all, 177 cycles were given, with 18 pts (49%) receiving ≥ 6 cycles and 12 pts (32%) 8 cycles. Neither grade 3/4 adverse events (AEs) related to N nor increase of D-related AEs were noted. Common grade 1/2 AEs included chills (65%). Eight pts (23%; 95% CI 12-39) had partial response (PR; 2 with PFI < 6 and 6 with PFI 6-12; median duration: 8.2 months). Fifteen pts had stable disease (SD, 43%; 10 with PFI < 6 and 5 with PFI 6-12; median duration: 4.9 months) for an overall disease control (DC, PR+SD) rate of 66%. Mean changes from baseline in target tumor size after 2, 4, 6, and 8 cycles were 2%, -54%, -69%, and -77%, respectively. Median PFS was 5.0 months (95% CI 3.1-6.9) and median OS was 17.0 months (10.4-23.6). In pts with PFI < 6 or 6-12, median PFS were 3.8 and 7.8 months (p=.03) and median OS were 14.3 and 20.1 months (p=.14), respectively. Pts with DC had longer median OS than those with early PD (24.0 and 4.9 months, respectively, p=.02). Longer PFI (p=.03) and higher PBLC (p=.01) were associated with better PFS, while OS correlated only with PBLC (p=.001). In the subset with PFI < 6, pts with PBLC ≥ or < 1.2/mL (1st quartile) had median PFS of 4.9 and 2.6 months (p=.02) and median OS of 15.8 and 4.3 months (p=.0001), respectivel Conclusions: A randomized phase II trial is currently testing D ± NGR-hTNF in pts with PFI < 6 (refractory/resistant). The role of PBLC as blood-based biomarker deserves further investigation.

Updated survival results of the randomized phase II study comparing cisplatin/capecitabine (CX) with epirubicin plus CX (ECX) in advanced gastric cancer (AGC).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 46-46 ◽  
Author(s):  
T. Lim ◽  
J. Yun ◽  
J. Lee ◽  
S. Park ◽  
J. Park ◽  
...  
Keyword(s):  
Performance Status ◽  
Randomized Study ◽  
Progression Free Survival ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
To Receive ◽  
Line Chemotherapy

46 Background: We previously reported results of a randomized study showing that CX is equally active to ECX in terms of progression-free survival (PFS) (Yun et al. Eur J Cancer. 2010). Here we report updated overall survival (OS) results with an additional 12 months' follow-up. Methods: Ninety-one chemotherapy-naïve patients with histologically-confirmed, measurable AGC were randomized to receive CX (cisplatin 75 mg/m2 iv on day 1 and capecitabine 1,000 mg/m2 bid po on days 1-14, n=45) or ECX (epirubicin 50 mg/m2 plus CX, n=44) every 3 weeks. After CX or ECX had failed, second-line chemotherapy (SLC) was recommended for all patients if their performance status was preserved. Results: Treatment duration was similar for both arms (4.4 for CX v 4.2 months for ECX). There was no relevant difference in the occurrence of overall grade 3 or 4 toxicities between the CX and ECX arms (80% v 78%, respectively; p=0.516). However, none in the CX and 12% in the ECX arm discontinued treatment because of toxicity. There were no significant differences in therapeutic efficacy between CX and ECX with respect to the response rate (38% v 37%, respectively), PFS (6.4 v 6.5 months), as well as OS (12.7 v 13.8 months; p=0.51). After failure, 60% of patients (26 CX and 28 ECX patients) received SLC. However, OS was not differed whether a patient was treated with SLC or not (13.1 v 11.2 months; p=0.94). Conclusions: The present analysis confirms previous findings that both CX and ECX appear to be comparatively active as first-line chemotherapy for AGC. Furthermore, the role of SLC in AGC warrants further evaluation. No significant financial relationships to disclose.

Comparison Of Treatment Outcomes with EPOCH-Rituximab Versus CHOP-Rituximab in Patients with De-novo Intermediate and High Risk International Prognostic Index(IPI)Diffuse Large B Cell Lymphoma(DLBCL): A Single Center Retrospective Analysis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5115-5115
Author(s):  
Hasmukh Jain ◽  
Manju Sengar ◽  
Hari Menon ◽  
Uma Dangi ◽  
Bhausaheb Bagal ◽  
...  
Keyword(s):  
High Risk ◽  
Treatment Outcomes ◽  
Disease Progression ◽  
Retrospective Analysis ◽  
Poor Prognosis ◽  
De Novo ◽  
Performance Status ◽  
Progression Free Survival ◽  
Free Survival

Abstract Poor prognosis DLBCL, including intermediate and high risk disease according to IPI accounts for approximately 20% of new cases of DLBCL. The addition of rituximab to conventional chemotherapy (CHOP) has improved the outcomes in this subset, with a 2-year overall survival (OS) of about 50%. However, 40-50% of these patients still have either primary refractory disease or relapse after an initial response. Rituximab-EPOCH (R-EPOCH), an infusional regimen has a dynamic dose adjustment strategy based on the hematopoietic nadir in previous cycle to achieve an optimal drug concentration. Phase II studies with R-EPOCH in untreated DLBCL with intermediate and high risk IPI have reported improved outcomes, with an estimated 2-year OS of 75% which appears superior to that of R-CHOP. Hence we analysed the outcomes of patients with de-novo, poor prognosis (intermediate and high risk IPI) DLBCL who received R-EPOCH and compared it to the  historical cohort of patients who were treated with R CHOP at our centre. Methods Treatment-naïve patients of DLBCL with intermediate or high risk IPI, registered at our centre between November 2011 to June 2013, who received R-EPOCH regimen, were included for the analysis. Case records were reviewed for – demography, histology, stage, bulk of disease, extranodal sites,  performance status, IPI, LDH, albumin, details of chemotherapy, grade ¾ toxicities (CTCAE version 4) and need for hospitalization.  Responses were evaluated at mid and end of chemotherapy. Overall and progression free survival were calculated. Similar analysis was done for poor prognosis DLBCL patients treated with R-CHOP between Jan 2007 to December 2010. Results Baseline characteristics and treatment outcomes of  32 patients (males-24, females-8) treated with R-EPOCH were compared to 42 patients (males-28, females-14) who received R- CHOP. Median age in R- EPOCH group was 47 years (range-20-75 years) versus 55 years (23-72 years )in R- CHOP. Performance status≥ 2 was seen in 47% in R- EPOCH as compared to 28% in R-CHOP group. Significant proportion of patients in R-EPOCH had bulky disease(81% versus  16%) and stage III/IV disease (90% versus 81%) as compared to R-CHOP. Patients with IPI of two represented 8(25%), IPI of three, 11(34%), and IPI of four and five, 10(32%) on R- EPOCH compared to 21(50%), 19(45%) and 2(5%) on R-CHOP, respectively. Serum albumin<3.5 gm/dL was seen in 10(32%) on R-EPOCH and 14(33%) on R-CHOP. LDH was elevated in all but two patients on R-EPOCH compared to 37(88%) patients on R-CHOP. Complete response was seen in 60%, and disease progression in 18% patients on R-EPOCH, compared to 59%, and 20% on R-CHOP respectively. There were 5 deaths on R-EPOCH, 3 due to toxicity and 2 due to disease progression, and in comparison there were 4 deaths on R-CHOP, all of them due to disease progression.  With a median follow up of 6 months, the estimated OS at 1 year is 74% and progression free survival (PFS) is 62% for patients on R- EPOCH. For patients on R- CHOP, with a median follow up of 31 months, 1 year OS is 68% and PFS is 64%. Conclusion Our retrospective analysis indicates that treatment with R-EPOCH regimen resulted in similar results as with R-CHOP regimen. However patients treated with R-EPOCH had more adverse features in terms of disease bulk, poor performance status and high IPI score. A prospective randomized comparison is warranted between these two regimens. Disclosures: No relevant conflicts of interest to declare.

scholarly journals CTNI-38. PAMIPARIB IN COMBINATION WITH RADIATION THERAPY (RT) AND/OR TEMOZOLOMIDE (TMZ) IN PATIENTS WITH NEWLY DIAGNOSED (ND) OR RECURRENT/REFRACTORY (R/R) GLIOBLASTOMA (GBM); PHASE 1B/2 STUDY UPDATE

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii51-ii51
Author(s):  
Anna Piotrowski ◽  
Vinay Puduvalli ◽  
Patrick Wen ◽  
Howard Colman ◽  
Jian Campian ◽  
...  
Keyword(s):  
Rest Period ◽  
Progression Free Survival ◽  
Free Survival ◽  
Synergistic Cytotoxicity ◽  
Common Grade ◽  
Duration Of Response ◽  
Phase 1B ◽  
Grade 3 ◽  
Parp 1

Abstract Pamiparib, an investigational, oral PARP 1/2 inhibitor, demonstrated preclinical brain penetration and synergistic cytotoxicity with TMZ. We report updated safety and antitumor data for pamiparib plus RT and/or TMZ in ND-GBM or R/R-GBM (SNO 2019, ACTR-39). This dose-escalation/expansion study includes three arms: A, pamiparib (2, 4, or 6 weeks) plus RT (6–7 weeks) in ND-GBM with unmethylated MGMT promoter (unmethylated-GBM); B, pamiparib (6 weeks) plus RT and increasing TMZ doses in Weeks 1 and 5 of RT in unmethylated ND-GBM; and C, pamiparib plus increasing TMZ doses in methylated/unmethylated R/R-GBM. Most patients in Arms A (expansion) and B received maintenance pamiparib plus TMZ after post-RT rest period at Arm C expansion. As of April 10, 2020, enrollment was complete (N=116; A, n=60; B, n=9; C, n=47). Median study follow-up was 11.3 mo (A/B) and 7.1 mo (C). Common grade ≥3 AEs were anemia (10%) in Arm A; decreased neutrophil and white blood cell count (each 22%) in B; anemia, fatigue, and decreased lymphocyte count (each 11%) in C. Brain edema (A) and pneumonia (C) (n=1 each) were fatal treatment-unrelated AEs. In ND-GBM, modified disease control rate (DCR following post-RT rest period) was 69.8% (95% CI, 55.7–81.7) overall, 68.8% (50.0–83.9) in A, and 80.0% (28.4–99.5) in B. Median duration of response was 5.1 mo (overall), 3.8 mo (A), and NE (B). In Arms A/B, median progression-free survival (PFS) and median overall survival (OS) were 4.4 mo and 12.7 mo, respectively; 12-mo OS rate, 54% (95% CI, 40–66). In R/R-GBM (Arm C), confirmed ORR was 9.1% (95% CI, 2.5–21.7); median PFS and OS were 1.9 mo and 7.3 mo, respectively; 6-mo PFS rate, 19% (95% CI, 9–32). These results showed a manageable safety profile for pamiparib +/- RT +/-TMZ; response and survival results support further evaluation of these combinations in GBM.

P14.58 Efficacy and safety of lomustine versus fotemustine as first and second line treament in relapsed glioblastoma patients

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii49-ii49
Author(s):  
M Domènech ◽  
C Fabregat ◽  
A Hernández ◽  
S del Barco ◽  
C Panciroli ◽  
...  
Keyword(s):  
Performance Status ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Second Line ◽  
Treatment Delays ◽  
Free Survival ◽  
Primary Brain Tumour ◽  
Grade 3 ◽  
Mild Toxicity

Abstract BACKGROUND Glioblastoma (GB) is the most aggressive primary brain tumour. Despite the survival benefit associated with adjuvant therapy, most of patients (pts) relapse after initial therapy. Nitrosoureas (NU) are the standard treatment at relapse in Europe. Both fotemustine (FM) (Addeo schema) and lomustine (LM) (administered orally every 6 weeks) are used in this context. MATERIAL AND METHODS This retrospective cohort study included pts diagnosed with GB treated with NU at relapse in four Catalonia hospitals from 2010 to 2020. Clinical and pathological data were collected from medical records. We analysed 6months-progression-free survival (6m-PFS), progression-free survival (PFS) and overall survival (OS) from the start of NU to progression or death respectively. Differences in toxicity grade using CTCAE v5.0 were analysed globally as ‘non-toxicity’, ‘mild toxicity (grade 1 or 2)’ and ‘high toxicity (grade 3 or 4)’. RESULTS We identified 236 GB pts with a median age of 58 years old. 29% of the pts presented MGMT promotor methylation and only 3%(n=7) had IDH mutation. After a median follow-up of 20 months, 94% of the pts were dead at the time of the analyses. At first line, 83 pts were treated with FM and 18 with LM. Pts treated with FM had better performance status (PS) than those treated with LM (p=.010). Median PFS was 2 months and 6m-PFS was 12% vs 6% in FM and LM group respectively (p=.87). Median OS was 3 months with LM vs 6 months with FM, with no statistically significant differences even adjusted for prognostic factors (p=.79 HR:0.9 CI 95% 0.41–1.96).At second line, 78 were treated with FM and 24 with LM, no differences between groups. Median PFS was 2 months in both groups and median OS was 3 vs 5 months for pts treated with LM vs FM respectively, with no significant differences. 6m-PFS was 13% for LM vs 0% for the FM group (p=.39).Pts received a mean of 1.7 cycles (every 6 weeks) and 4.1 cycles (every 2 weeks) in LM and FM group, respectively. Thrombocytopenia was the most common serious side-effect, with a higher proportion of grade 1–2 toxicity in the FM group (p=.03) that also required more treatment delays (p=.01). CONCLUSION Despite being retrospective study and a few pts were treated with LM, there were no differences neither in PFS nor in OS in pts treated with LM vs FM at first or second line. Higher G1-2 thrombocytopenia was shown in the FM group probably due to a higher number of hematology samples collected.

Results of the VENUS study: Bevacizumab efficacy and safety in platinum-sensitive recurrent ovarian cancer (OC)—A real-life ambispective study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5540-5540
Author(s):  
Isabelle Laure Ray-Coquard ◽  
Jerome Alexandre ◽  
Francois Goldwasser ◽  
Jean-Philippe Spano ◽  
Dominique Berton-Rigaud ◽  
...  
Keyword(s):  
De Novo ◽  
Real Life ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Free Survival ◽  
Life Study ◽  
Platinum Sensitive ◽  
Real Life Setting ◽  
Grade 3

5540 Background: The VENUS study reports on the efficacy/safety of bevacizumab (Bev) in patients (pts) treated in the real-life setting. Methods: In this multicentric observational ambispective VENUS study, all Pts were naive of any antiVEGF and received Bev +/- chemotherapy. Pts were followed until progression or death, for a maximum of 3 years since Bev initiation. De novo side effects were defined as symptoms for which patients were naïve at baseline. Results: 148 OC pts were included (27 centres), 10 excluded and 8 were lost of follow-up. 52 were retrospective. Median age 64 years (55-70). 84.1% were advanced. Median duration of Bev was 8.6 months, min 1 max 36 months. Initial Bev dose was 15 mg/kg Q3W for 65.3%, 10.0 for 22.5%, 7.5 for 10.2% and 5.0 for 2%. 2 pts presented with thrombotic micro-angiopathy (1.4%). Before Bev, hypertension (HTN) was present in 28.9%; proteinuria in 11.3%. Incidence of de novo HTN was 25%. 43 pts (31.2%) experienced de novo Grade 1-2 Pu, for a total of 56 events, no grade 3-4 was observed. A total of 12 Grade 4 events occurred: 9 neutropenia and 3 thrombopenia. Mean overall survival (OS) and progression free survival (PFS) were 30.0 and 13.3 months, respectively. Conclusions: 1) 1/3 of pts were treated at low doses in this real-life study; 2) safety of Bev in real-life was manageable and as expected, 3) OS and PFS were consistent with those reported in the OCEANS study: PFS 12.4 and OS 33.6 months but lower than in the GOG-0213 study: PFS 13.8 and OS 42.6 months. De novo events recorded during follow-up. [Table: see text]

scholarly journals Efficacy, safety and prognostic factors in patients with refractory metastatic colorectal cancer treated with trifluridine/tipiracil plus bevacizumab in a real-world setting

2022 ◽  
Author(s):  
Nieves Martínez-Lago ◽  
Teresa Calleja Chucla ◽  
Beatriz Alonso de Castro ◽  
Rafael Varela Ponte ◽  
Cristina Reboredo Rendo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Common Grade ◽  
Third Line ◽  
Grade 3

Abstract We evaluated the efficacy and safety of trifluridine/tipiracil (TAS-102) plus bevacizumab in treating refractory metastatic colorectal cancer (mCRC) in a retrospective, observational study. Patients refractory or intolerant to standard therapies received TAS-102 (30–35 mg/m2 twice daily on days 1–5 and days 8–12 every 28 days) plus bevacizumab 5 mg/kg on days 1 and 15. Clinical and pathological characteristics, overall response rate (ORR) and disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) data were collected and analysed. Thirty-five patients were treated from July 2019 to October 2021 (median age 64 years). The majority of patients (68.6%) were receiving TAS-102 plus bevacizumab as third-line treatment. Patients received a median of 4 (range 2–15) cycles of treatment. Among 31 patients evaluable for response (88.6%), ORR and DCR were 3.2% and 51.6%, respectively. After a median 11.6 months’ follow-up, median PFS was 4.3 (95% confidence interval [CI] 3.4–5.1) months and median OS was 9.3 (95% CI 6.6–12.1) months. The most common grade 3–4 toxicities were neutropenia, asthenia and nausea/vomiting, and there were no treatment-related deaths. This real-world study confirms the efficacy and safety of TAS-102 plus bevacizumab in patients with refractory mCRC.

Randomized phase II trial of NGR-hTNF in combination with standard chemotherapy in previously untreated non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8035-8035
Author(s):  
Vanesa Gregorc ◽  
Nicoletta Zilembo ◽  
Francesco Grossi ◽  
Tommaso M De Pas ◽  
Gilda Rossoni ◽  
...  
Keyword(s):  
Synergistic Effects ◽  
Pulmonary Hemorrhage ◽  
Progression Free Survival ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Baseline Characteristics ◽  
Grade 3 ◽  
To Receive ◽  
Clinical Trial Information

8035 Background: NGR-hTNF, a selective antivascular agent, induces at low dose an initial vascular normalization that greatly enhances the intratumoral chemotherapy uptake, with synergistic effects that were noted especially in combination with cisplatin and gemcitabine. Methods: Chemo-naive patients (pts) with advanced NSCLC were stratified by histology (nonsquamous or squamous) and PS (0 or 1) and randomly assigned to receive cisplatin 80 mg/m2/d1 plus either pemetrexed 500 mg/m2/d1 (nonsquamous) or gemcitabine 1,250 mg/m2/d1+8 (squamous) every 3 weeks (q3w) for 6 cycles, with (arm A) or without (arm B) NGR-hTNF given at 0.8 μg/m2/d1/q3w until progression. Progression-free survival (PFS) was primary aim (1-β=80%, 1-sided α=10%, n=102). Secondary aims comprised adverse events (AEs), response rate (RR), and overall survival (OS). Results: Baseline characteristics in arm A (n=62) vs B (n=59) were: median age: 62 vs 63 years; men: 37 vs 39; PS 1: 23 vs 23; squamous: 18 v 17; smokers: 41 vs 43. For the nonsquamous stratum, 299 cycles were given in arm A (mean 7.0; range 1-20) and 192 in arm B (4.8; 1-6), while for the squamous stratum, 113 in arm A (6.7; 1-31) and 52 in arm B (3.5; 1-6). Rates of grade 3/4 AEs were similar (arm A vs B): neutropenia 13% vs 18%, anaemia 7% vs 4% and fatigue 7% vs 11%. No grade 3/4 AEs related to NGR-hTNF or bleeding/pulmonary hemorrhage events were reported in the squamous subset. With median follow-up time of 24.2 months, median PFS (5.8 vs 5.6 months; HR=0.92), RR (25% vs 21%) and 1-year OS (53% vs 53%) were similar between the two treatment arms. However, by predefined analysis in the squamous stratum, median PFS was 5.6 months for arm A and 4.3 months for arm B (hazard ratio, HR=0.75) and median OS was 14.2 months for arm A and 9.7 months for arm B (HR=0.49; p=0.07). In pts with squamous histology, RR was 38% for arm A and 27% for arm B (odds ratio=1.6), while the median changes in tumor size on treatment from baseline to 2nd, 4th and 6th cycle for arm A vs B were -32% vs -20%, -41% vs -19%, and -42% vs -14%, respectively. Conclusions: Clinical tolerability and benefit were noted in squamous NSCLC with NGR-hTNF plus cisplatin and gemcitabine, which deserve further investigation. Clinical trial information: NCT00994097.

A phase 2 study of s-1 plus leucovorin in patients with untreated advanced cholangiocarcinoma (CCA).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 467-467
Author(s):  
Suebpong Tanasanvimon ◽  
Teerapat Ungtrakul ◽  
Nattaya Poovorawan ◽  
Napa Parinyanitikul ◽  
Chanida Vinayanuwattikun ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Primary Endpoints ◽  
Phase 2 Study ◽  
Common Grade ◽  
Secondary Endpoints ◽  
Grade 3

467 Background: Patients with CCA usually present with advanced disease leading to the grave prognosis. Currently, cisplatin and gemcitabine is the standard treatment in advanced CCA. However, the CCA treatment outcomes are still poor and the options of treatment are quite limited. This study aimed to explore the efficacy and safety of S-1 plus leucovorin in patients with untreated advanced CCA. Methods: This single-arm two-center phase 2 study evaluated the efficacy and safety of S-1 40, 50 and 60 mg according to body surface area and leucovorin 15 mg , both given orally twice daily for one week, repeated every two weeks. Treatment was continued until complete 12 cycles, disease progression or unacceptable toxicity. The primary endpoints were overall response rate (ORR) and disease control rate (DCR) per RECIST version 1.1. The secondary endpoints were progression free survival (PFS), overall survival (OS) and toxicity. Results: Of total 32 patients and a median follow up time of 9.5 months, the ORR was 25% (95%CI 9.1-40.9) and the DCR was 62.5% (95% CI 44.8-80.2). In 25 response evaluable patients, the ORR was 32% (95% CI 12.4-51.7). The PFS was 8.0 (95%CI 5.59-10.4) months. The OS was 11.0 (95%CI 9.47-12.53). The most common grade 3 or 4 toxicities were anemia, mucositis and diarrhea. There was one patient discontinuing treatment due to treatment related toxicity. Conclusions: S-1 plus leucovorin was active and tolerable in patients with advanced CCA. Clinical trial information: TCTR20160313001.

A randomized phase II study of gemcitabine (G) alone or with pazopanib (P) in refractory soft tissue sarcoma (STS).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11515-11515
Author(s):  
Christopher W. Ryan ◽  
Catherine Degnin ◽  
Lee D. Cranmer ◽  
Yiyi Chen ◽  
Seth Pollack ◽  
...  
Keyword(s):  
Statistical Power ◽  
Response Rate ◽  
Progression Free Survival ◽  
Wilcoxon Test ◽  
Double Blind Study ◽  
Double Blind ◽  
Randomized Phase Ii ◽  
Common Grade ◽  
Grade 3

11515 Background: Both G and P are active single-agents in the treatment of STS. We hypothesized that the anti-VEGF-R activity of P could augment the efficacy of G and conducted this study of G+P vs G+placebo (0). Methods: In this multi-center, double-blind study, eligibility included metastatic STS with receipt of 1–3 prior systemic regimens inclusive of an anthracycline. Patients (pts) were stratified by sarcoma subtype (liposarcoma (LPS) vs. other) and study site, then randomly assigned 1:1 to receive G 1000 mg/m2 IV over 30 minutes on days 1 and 8 every 21 days plus either P 800 mg PO or matching 0 daily. The primary endpoint was progression-free survival (PFS). Results: 54 pts were accrued from 2012–2019, Accrual was halted prior to the planned N of 80 due to withdrawal of funding. There were no differences in pt characteristics between the two arms including age (median = 60), sex (M/F 52/48%), histology (LPS 30%, leiomyosarcoma 26%, UPS 15%, synovial 11%, other 17%) and number of prior systemic therapies (median = 1). With a median follow-up of 19.1 months, PFS favored G+P and was significant using the Gehan-Wilcoxon test which favorably weighs earlier events (table). The response rate was 6.9% on the G+P arm and 8.0% on the G+0 arm; response rate was 22% for LPS treated with G+P. The most common grade ≥3 AEs (G+P v G+0) were: neutropenia (41% vs 40), hypertension (17% v 4), anemia (7% v 12). One patient died of hepatic failure on the G+P arm. Conclusions: This study demonstrated improved PFS with G+P as compared with G alone. Early termination limited statistical power. G+P is active in LPS, although P regulatory labeling currently limits use for LPS. Clinical trial information: NCT01532687 . [Table: see text]

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