Randomized double blind (DB) placebo (Plcb) controlled phase III study assessing the efficacy of xaliproden (X) in reducing the cumulative peripheral sensory neuropathy (PSN) induced by the oxaliplatin (Ox) and 5-FU/LV combination (FOLFOX4) in first-line treatment of patients (pts) with metastatic colorectal cancer (MCRC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3507-3507 ◽  
Author(s):  
J. Cassidy ◽  
G. A. Bjarnason ◽  
T. Hickish ◽  
C. Topham ◽  
M. Provencio ◽  
...  
Keyword(s):  
Cumulative Dose ◽  
Significant Risk ◽  
Dose Intensity ◽  
Sensory Neuropathy ◽  
Median Number ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Grade 3

3507 Background: X, an orally administered non-peptide neurotrophic agent developed by sanofi-aventis, was shown in vitro to minimize neuritic damage induced by Ox (co-culture of Schwann cells and dorsal roots ganglia explant). The probability of occurrence of Grade (Gr) 3–4 PSN at a cumulative dose of Ox of 1000 mg/m2, was consistently reported to be of 18–20%. Methods: First line MCRC pts were randomized to receive, in a DB fashion, FOLFOX4 and either Plcb or X 1mg daily. X was administered from the 1st day of chemotherapy till 15 days post last Ox cycle. Co-primary objectives were reduction in the risk of occurrence of Gr 3–4 PSN relative to cumulative dose of Ox (Kaplan-Meier method) and non-inferiority in response rate (RR). Secondary endpoints included evaluation of sensory action potential (SAP) and safety. Results: From July 2002 to May 2004, 649 pts were randomized (324 Plcb, 325 X). Pts characteristics were well balanced across arms, median number of Ox cycles was 12 in both arms, median relative dose intensity (%) was 83.8 (Plcb) and 85.2 (X). A significant risk reduction of 39% in the probability of Grade 3–4 PSN in favor of X was reported (hazard ratio [95% CI] = 0.61 [0.40; 0.93], p= 0.0203). Overall RR [95 % CI] was: Plcb 42.6% [37.1; 48.2] and X 44.9% [39.4; 50.6]. As prospectively defined in the protocol, the lower bound of the CI of the RR ratio above 0.8 confirms noninferiority in RR (1.055 [0.88; 1.26]). In both arms the mean % of change in SAP worsens as a function of PSN severity. 17.3 (Plcb) and 13.5% (X) of the pts discontinued Ox because of PSN. Severe toxicities (% Gr 3–4), reported with a ≥2% difference between arms, were (plcb vs X): diarrhea 10.9 vs 13.0, pulmonary embolism 0.9 vs 3.1, fatigue 3.7 vs 1.5, neutropenia 43.0 vs 37.8. Conclusion: X was shown to be efficient in reducing the risk of Grade 3–4 oxaliplatin-induced PSN without impacting FOLFOX4 antitumor activity. No significant financial relationships to disclose.

Aflibercept versus placebo in combination with docetaxel/prednisone for first-line treatment of men with metastatic castration-resistant prostate cancer (mCRPC): Results from the multinational phase III trial (VENICE).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 13-13 ◽  
Author(s):  
Ian Tannock ◽  
Karim Fizazi ◽  
Sergei Ivanov ◽  
Camilla Thellenberg Karlsson ◽  
Aude Flechon ◽  
...  
Keyword(s):  
Oral Prednisone ◽  
Dose Intensity ◽  
Median Number ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Double Blind ◽  
Number Of Cycles ◽  
Ecog Ps ◽  
Line Chemotherapy

13 Background: Docetaxel/prednisone is standard first-line chemotherapy for mCRPC. Aflibercept (known as ziv-aflibercept in the US) is a recombinant human fusion protein that binds VEGF-A, VEGF-B and Placental Growth Factor (PlGF), thereby inhibiting angiogenesis. Methods: VENICE was a double-blind, randomized phase III study with overall survival (OS) as primary endpoint. Men with mCRPC, ECOG PS 0-2, adequate organ function and no prior cytotoxic therapy were treated with docetaxel (75 mg/m² iv q3w) and oral prednisone (5mg bid) and randomized double blind 1:1 to receive aflibercept (A) 6 mg/kg or placebo (Pbo), IV every 3 weeks. Pts were stratified by ECOG PS (0-1 vs 2). For final OS analysis, 873 deaths were required to detect a hazard ratio (HR) of 0.8 with 90% power (overall 2-sided α = 0.05). Results: From Aug 2007 to Feb 2010, 1224 patients (median age 68 yr, PS 0-1 96%) were randomized. Baseline characteristics were well balanced between arms. Median number of cycles was 8 (A) and 9 (Pbo). Median relative dose intensity was >0.93 for A, Pbo and docetaxel. At final cut-off, median follow-up was 35.4 mos and 873 pts had died. Results for primary and key secondary endpoints with confidence intervals are in the table. Higher incidence of all grade hypertension, stomatitis, appetite disorders, diarrhea, dehydration, epistaxis, dysphonia, cough, headache and infections was observed in the aflibercept arm. Conclusions: Aflibercept in combination with docetaxel/prednisone given as first line chemotherapy for mCRPC did not lead to a statistically significant improvement in OS and added toxicity. (NCT00519285 sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.) Clinical trial information: NCT00519285. [Table: see text]

Phase III Multicenter Randomized Trial of Oxaliplatin Added to Chronomodulated Fluorouracil–Leucovorin as First-Line Treatment of Metastatic Colorectal Cancer

2000 ◽  
Vol 18 (1) ◽  
pp. 136-136 ◽  
Author(s):  
S. Giacchetti ◽  
B. Perpoint ◽  
R. Zidani ◽  
N. Le Bail ◽  
R. Faggiuolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Phase Iii ◽  
Line Treatment ◽  
Survival Times ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

PURPOSE: To study how adding oxaliplatin (l-OHP) to chronomodulated fluorouracil (5-FU)–leucovorin (LV) affected the objective response rate, as first-line treatment of metastatic colorectal cancer. PATIENTS AND METHODS: Two hundred patients from 15 institutions in four countries were randomly assigned to receive a 5-day course of chronomodulated 5-FU and LV (700 and 300 mg/m2/d, respectively; peak delivery rate at 0400 hours) with or without l-OHP on the first day of each course (125 mg/m2, as a 6-hour infusion). Each course was repeated every 21 days. Response was assessed by extramural review of computed tomography scans. RESULTS: Grade 3 to 4 toxicity from 5-FU–LV occurred in ≤ 5% of the patients (≤ 1% of the courses). Grade 3 to 4 diarrhea occurred in 43% of the patients given l-OHP (10% of the courses), and less than 2% of the patients had severe hematotoxicity. Thirteen percent of the patients had moderate functional impairment from peripheral sensory neuropathy. Sixteen percent of the patients receiving 5-FU–LV had an objective response (95% confidence interval [CI], 9% to 24%), compared with 53% of those receiving additional l-OHP (95% CI, 42% to 63%) (P < .001). The median progression-free survival time was 6.1 months with 5-FU–LV (range, 4.1 to 7.4 months) and 8.7 months (7.4 to 9.2 months) with l-OHP and 5-FU–LV (P = .048). Median survival times were 19.9 and 19.4 months, respectively. CONCLUSION: By chronomodulating 5-FU–LV, we were able to add l-OHP without compromising dose-intensities. l-OHP significantly improved the antitumor efficacy of this regimen.

JUPITER-02: Randomized, double-blind, phase III study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC).

2021 ◽  
Vol 39 (18_suppl) ◽  
pp. LBA2-LBA2
Author(s):  
Rui-hua Xu ◽  
Hai-Qiang Mai ◽  
Qiu-Yan Chen ◽  
Dongping Chen ◽  
Chaosu Hu ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Double Blind ◽  
Grade 3 ◽  
First Line Treatment

LBA2 Background: Gemcitabine-cisplatin (GP) chemotherapy is the standard 1st line treatment for locally advanced, recurrent or metastatic (r/m) NPC. Toripalimab, a humanized IgG4K monoclonal antibody specific for PD-1, provided durable responses in patients (pts) with r/m NPC as monotherapy in the ≥2nd line setting (POLARIS-02 study). The results of JUPITER-02, a randomized, placebo-controlled, double-blinded Phase III trial of toripalimab in combination with GP chemotherapy as first-line treatment for r/m NPC are summarized. Methods: Pts with advanced NPC with no prior chemotherapy in the r/m setting were randomized (1:1) to receive toripalimab 240 mg or placebo d1 in combination with gemcitabine 1000 mg/m2 d1, d8 and cisplatin 80 mg/m2 d1 every 3 weeks (Q3W) for up to 6 cycles, followed by monotherapy with toripalimab or placebo Q3W until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors were ECOG PS (0 vs. 1) and extent of disease (recurrent vs. primary metastatic) at enrollment. Progression-free survival (PFS) and response were assessed by independent review committee (IRC) per RECIST v1.1. The primary endpoint was PFS by IRC in the ITT population. Secondary end points included ORR, DOR and OS. There was one prespecified interim analysis of PFS at 130 PFS events with a planned final analysis at 200 PFS events. Results: 289 pts were randomized: 146 to the toripalimab arm and 143 to the placebo arm. By May 30, 2020 as the interim analysis cutoff date, the median treatment duration was 39 weeks in the toripalimab arm and 36 weeks in the placebo arm. A significant improvement in PFS was detected for the toripalimab arm compared to the placebo arm (HR = 0.52 [95% CI: 0.36-0.74] two-sided p = 0.0003), with median PFS of 11.7 vs. 8.0 months. The 1-year PFS rates were 49% and 28% respectively. An improvement in PFS was observed across relevant subgroups, including all PD-L1 subgroups. The ORR was 77.4% vs. 66.4% (P = 0.033) and the median DOR was 10.0 vs. 5.7 months (HR = 0.50 [95% CI: 0.33-0.78]). As of Jan 15, 2021, OS was not mature, with 25 deaths in the toripalimab arm and 35 in the placebo arm (HR = 0.68 [95% CI: 0.41-1.14], P = 0.14). The incidence of Grade ≥3 adverse events (AEs) (89.0% vs 89.5%); AEs leading to discontinuation of toripalimab/placebo (7.5% vs 4.9%); and fatal AEs (2.7% vs 2.8%) were similar between two arms; however, immune-related (irAEs) (39.7% vs. 18.9%) and Grade ≥3 irAEs (7.5% vs. 0.7%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to GP chemotherapy as 1st-line treatment for pts with advanced NPC provided superior PFS and ORR and longer DOR than GP alone with a manageable safety profile. These results support the use of toripalimab with GP chemotherapy as the new standard care for this population. Clinical trial information: NCT03581786.

Results of a phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim (PEG) in patients (pts) receiving first-line FOLFOX or FOLFIRI and bevacizumab (B) for colorectal cancer (CRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3575-3575
Author(s):  
Tamas Pinter ◽  
Esteban Abella ◽  
Alvydas Cesas ◽  
Adina Croitoru ◽  
Jochen Decaestecker ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Free Survival ◽  
Clinically Significant ◽  
Grade 3

3575 Background: The literature reports that adding biologics to chemotherapy (ctx) may increase the incidence of clinically significant neutropenia. his trial was conducted to evaluate the efficacy of PEG in reducing the incidence of febrile neutropenia (FN) in pts with locally-advanced (LA) or metastatic (m)CRC receiving first-line treatment with either FOLFOX/B or FOLFIRI/B. Methods: Key eligibility: ≥ 18 years old; measurable, nonresectable CRC per RECIST 1.1. Pts were randomly assigned 1:1 to either placebo or 6 mg PEG ~24 h after ctx/B. The study treatment period included four Q2W cycles, but pts could continue their assigned regimen until progression. Pts were stratified by region (North America vs rest of world), stage (LA vs mCRC), and ctx (FOLFOX vs FOLFIRI). Estimated sample size (N = 800) was based on the expected incidence of grade 3/4 FN (primary endpoint) across the first 4 cycles of ctx/B, powered for PEG superiority over placebo. Other endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: 845 pts were randomized (Nov 2009 to Jan 2012) and received study treatment; 783 pts completed 4 cycles of ctx/B. Median age was 61 years; 512 (61%) pts were male; 819 (97%) had mCRC; 414 (49%) received FOLFOX, and 431 (51%) received FOLFIRI. Grade 3/4 FN (first 4 cycles) for placebo vs PEG was 5.7% vs 2.4%; OR 0.41; p = 0.014. A similar incidence of other ≥ grade 3 adverse events was seen in both arms (28% placebo; 27% PEG). See table for additional results. Conclusions: PEG significantly reduced the incidence of grade 3/4 FN in this pt population receiving standard ctx/B for CRC. Follow-up is ongoing. Clinical trial information: NCT00911170. [Table: see text]

Phase III study of nab-paclitaxel (nab-P) plus gemcitabine (Gem) versus Gem alone in patients (pts) with metastatic pancreatic adenocarcinoma (mPC): Subgroup analysis of Canadian pts from the MPACT trial.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 439-439
Author(s):  
Mustapha Ali Tehfe ◽  
Scot D. Dowden ◽  
Hagen F. Kennecke ◽  
Robert Hassan El-Maraghi ◽  
Bernard Lesperance ◽  
...  
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Pancreatic Head ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Common Grade ◽  
Grade 3 ◽  
Intent To Treat

439 Background: Weekly nab-P + Gem is a new option for first-line treatment (Tx) of mPC. In the MPACT trial, nab-P/Gem demonstrated superior overall survival (OS; primary endpoint) vs Gem alone as first-line Tx of mPC (Table). Here we report a subgroup analyses evaluating the efficacy and safety outcomes with nab-P + Gem vs Gem alone from the Canadian cohort of the MPACT trial. Methods: Previously untreated pts (N = 861) with mPC were randomized 1:1 (stratified by Karnofsky Performance Status [KPS], region, and the presence of liver metastases) to receive nab-P 125 mg/m2 + Gem 1000 mg/m2 on days 1, 8, and 15 of each 28-day cycle or Gem 1000 mg/m2 weekly for 7 weeks followed by 1 week of rest (cycle 1) and then days 1, 8, and 15 of each 28-day cycle (cycle ≥ 2). Results: 63 pts from Canada enrolled in the MPACT trial. Baseline pt characteristics were well balanced. Median age was 61 years and KPS was similar for both groups and comparable to the intent-to-treat (ITT) populations. Primary lesion in the pancreatic head was more common among pts in the nab-P + Gem vs Gem arm (55% vs 30%); use of biliary stent was similar (33% nab-P + Gem; 27% Gem). Median OS and progression-free survival (PFS) were longer with nab-P + Gem vs Gem (Table). Median Tx duration was 4.2 mo with nab-P + Gem vs 3.2 mo with Gem. Use of subsequent therapy was 30% in the nab-P + Gem arm vs 43% in the Gem arm. The median relative dose intensity for Gem was similar in each arm (81% nab-P + Gem vs 85% Gem). The most common grade ≥ 3 AEs for nab-P + Gem vs Gem were neutropenia (22% vs 10%), fatigue (34% vs 33%), and neuropathy (25% vs 0%). Conclusions: Canadian pts participating in MPACT were similar to the ITT population and nab-P + Gem was well tolerated and showed improved median OS, PFS, and ORR vs Gem alone, although not statistically significant (likely due to the small number of pts). Clinical trial information: NCT00844649. [Table: see text]

Capecitabine plus irinotecan versus 5-FU/FA/irinotecan ± celecoxib in first line treatment of metastatic colorectal cancer (CRC). Long-term results of the prospective multicenter EORTC phase III study 40015

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3577-3577 ◽  
Author(s):  
J. De Grève ◽  
C. Koehne ◽  
J. Hartmann ◽  
I. Lang ◽  
P. Vergauwe ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Dose Intensity ◽  
Median Number ◽  
Small Sample ◽  
Phase Iii ◽  
Long Term Results ◽  
Safety Issues ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stratified Analysis

3577 Background: Oral fluoropyrimidines in combination with irinotecan may be an alternative to infusional 5-FU/FA+irinotecan. Cox-2 inhibitors may enhance the antineoplastic activity of chemotherapy (CT). Methods: Patients with ECOG PS<2, age>18 and measurable disease were randomised in a 2×2 factorial design to FOLFIRI (Douillard’s regimen) or capecitabine 2×1g/m2 d1–14 plus irinotecan 250mg/m2 d1, qd22 (CAPIRI), and to daily celecoxib 2x400mg (C) or placebo (P). 692 patients were planned to compare PFS as primary endpoint. The trial was suspended after 85 pts (44 CAPIRI and 41 FOLFIRI) due to the occurrence of 8 fatal events unrelated to disease progression (Köhne, ASCO 2005, A3525). Results: Baseline characteristics were well balanced. Three pts did not start treatment. Of the pts who started CT, 53% (23/43) in the CAPIRI and 33% (13/39) in the FOLFIRI arms required a dose reduction. Grade ≥3 diarrhoea occurred in 37% (16/43) and 13 % (4/39) on CAPIRI and FOLFIRI, respectively. Median number of CT cycles: 3 (CAPIRI) and 5 (FOLFIRI). Median dose intensity for irinotecan: 83% (CAPIRI) and 85% (FOLFIRI). Response rate (RR): 5/23 (22%) in CAPIRI+C, 10/21 (48%) in CAPIRI+P, 6/19 (32%) in FOLFIRI+C and 10/22 (45%) in FOLFIRI+C. RR for CAPIRI vs FOLFIRI: 15/44 (34%) versus 16/41 (39%), RR for Celecoxib vs Placebo: 11/42 (26%) vs. 20/43 (46 %). Median PFS: 5.9 months (95% CI: 4.4–8.9) with CAPIRI vs 9.6 months (95% CI: 6.9–11.8) with FOLFIRI (HR=1.31, 95%CI: 0.8–2.1), and 6.9 months (95% CI: 5.5–10.4) with C vs 7.8 months (95% CI: 6.0–12.0) with P (HR=1.1, 95%CI: 0.7–1.8). Median OS: 14.8 months (95% CI: 10.7–18.3) with CAPIRI vs 19.9 months (95% CI: 18.9-n.a.) with FOLFIRI (HR=3.2, 95%CI: 1.4–7.3), and 18.3 months (95% CI: 10.2-n.a.) with C versus 19.9 months (95% CI: 16.7-n.a.) with P (HR=1.25, 95%CI: 0.6–2.6). Conclusions: The data suggest that celecoxib might reduce response to CT and this warrants further preclinical investigation. The stratified analysis failed to demonstrate the non-inferiority of CAPIRI as compared to FOLFIRI. Small sample size and confounding safety issues prevent us from drawing definitive conclusions. Results of larger studies would be needed. No significant financial relationships to disclose.

PALETTE: A randomized, double-blind, phase III trial of pazopanib versus placebo in patients (pts) with soft-tissue sarcoma (STS) whose disease has progressed during or following prior chemotherapy—An EORTC STBSG Global Network Study (EORTC 62072).

2011 ◽  
Vol 29 (18_suppl) ◽  
pp. LBA10002-LBA10002 ◽  
Author(s):  
W. T. Van Der Graaf ◽  
J. Blay ◽  
S. P. Chawla ◽  
D. Kim ◽  
B. Bui Nguyen ◽  
...  
Keyword(s):  
Single Agent ◽  
Angiogenesis Inhibitor ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Global Network ◽  
Phase Iii ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Independent Review ◽  
Grade 3

LBA10002 Background: Pazopanib, a multi targeted angiogenesis inhibitor, has demonstrated single-agent activity in pts with advanced STS. The efficacy and safety of pazopanib versus placebo as second or later line treatment were evaluated in pts with metastatic STS in a multi-center, international, double-blind, placebo-controlled phase III trial. Methods: Pts ≥18 years of age with angiogenesis inhibitor-naïve, histologically proven, metastatic STS, who failed at least one anthracycline containing regimen, could enter the study. They should have ≥1 measurable baseline lesion (per RECIST v1.0), WHO PS 0-1, adequate bone marrow, coagulation, hepatic and renal function, no poorly controlled hypertension, no bleeding diathesis, and no CNS involvement. The study has been conducted by EORTC and GSK in collaboration with 72 sarcoma centers worldwide. Pts were randomized 2:1 to receive either pazopanib 800 mg once daily or placebo until tumor progression, unacceptable toxicity, death, or pt’s request. Results: A total of 369 randomized pts (246 pazopanib, 123 placebo), median age of 56 years, participated in the study (EORTC 45 %, other 55%). Median duration of follow-up at clinical cut-off date is 15 months. The primary endpoint of progression-free survival (PFS) per independent review is significantly prolonged with pazopanib (median: 20 vs 7 weeks; HR=0.31, 95% CI 0.24-0.40 ; P<0.0001). The interim analysis for overall survival shows a statistically non-significant improvement of pazopanib vs placebo (median: 11.9 vs 10.4 months, HR=0.83, 95% CI 0.62-1.09). Main on-therapy grade 3-4 toxicities in the pazopanib vs placebo arm respectively: fatigue (13%, 6%), hypertension (7%, nil), anorexia (6%, nil), and diarrhea (5%, 1%). Similarly, thromboembolic events (grade 3-5 ) (3%, 2%), LVEF drop of >15% (8%, 3%). Median relative dose intensity of pazopanib was 768 mg daily. Conclusions: Pazopanib is an active drug in anthracycline pretreated metastatic STS pts with an increase in median PFS of 13 weeks.

Meta-analysis of anti-VEGF class adverse events from three double-blind (db), placebo (pbo)-controlled phase III trials with IV aflibercept (Afl).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3579-3579 ◽  
Author(s):  
Josep Tabernero ◽  
Carmen Joseph Allegra ◽  
Philippe R Rougier ◽  
Giorgio Scagliotti ◽  
Philip Agop Philip ◽  
...  
Keyword(s):  
Adverse Events ◽  
Metastatic Cancer ◽  
Meta Analysis ◽  
Safety Data ◽  
Dose Intensity ◽  
Phase Iii ◽  
Double Blind ◽  
Anti Vegf ◽  
Increased Risk ◽  
Grade 3

3579 Background: Three db, pbo-controlled studies were conducted with IV Afl in metastatic cancer patients (pts) (colorectal [CRC], Afl + FOLFIRI [WCGC 2011, abstract O-0024]; lung [LC], Afl + docetaxel [WCLC 2011, abstract 511]; and pancreatic [PC], Afl + gemcitabine [WCGC 2009 abstract O-0006]). Each study used the same weekly Afl dose intensity (4 mg/kg q2w for CRC and PC; 6 mg/kg q3w for LC). A safety meta-analysis of anti-VEGF class adverse events (AEs) was performed on data from these studies. Methods: A fixed-effect logistic regression model was used, including study, treatment, and study-by-treatment interaction factors as covariates to test the consistency of treatment effect across studies for each of the considered AE. When no evidence of heterogeneity of treatment effects was found across studies, relative risks (RRs) and 95% confidence intervals (CIs) were estimated. Summary incidences (% of pts) and RR are presented for NCI grade 3-4 events. Results: Safety data from a total of 2662 pts (Afl, 1333; pbo, 1329) were included for analysis. Among pts treated with Afl, 0.4 and 0.5% experienced grade 4 hypertension and nephrotic syndrome, respectively. Conclusions: The addition of Afl to concurrent chemotherapies did not increase the risk of VTE. The risk of grade 3-4 anti-VEGF class AEs was increased when adding Afl to concurrent chemotherapies. This increased risk was statistically significant only for hypertension, proteinuria, and hemorrhage. Further analyses, when more data are available, should improve the precision of these results. [Table: see text]

A phase III trial of ganitumab (GAN, AMG 479) with gemcitabine (G) as first-line treatment (tx) in patients (pts) with metastatic pancreatic cancer (MPC): An analysis of safety from the GAMMA trial (GEM and AMG 479 in Metastatic Adenocarcinoma of the Pancreas).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4042-4042 ◽  
Author(s):  
Charles S. Fuchs ◽  
Masafumi Ikeda ◽  
Gyorgy Bodoky ◽  
Takuji Okusaka ◽  
Shinichi Ohkawa ◽  
...  
Keyword(s):  
Human Monoclonal Antibody ◽  
Data Monitoring Committee ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Double Blind Study ◽  
First Line ◽  
Double Blind ◽  
Patient Reported ◽  
Grade 3 ◽  
Ecog Ps

4042 Background: GAN is an investigational, fully human, monoclonal antibody inhibitor of IGF1R. GAMMA is assessing the safety and efficacy of GAN plus G as first-line tx in MPC pts (ClinicalTrials.gov ID: NCT01231347). Methods: This is an ongoing, global, phase III, double-blind study. Pts are randomized 2:2:1 to receive placebo, GAN 12 mg/kg, or GAN 20 mg/kg (IV; days 1 and 15 Q28D) with G 1000 mg/m2 (IV; days 1, 8, and 15 Q28D). The planned sample size is 825. Primary endpoint: overall survival. Key secondary endpoints: progression-free survival, 1-year survival rate, patient-reported outcomes, and safety. This study includes multiple planned safety analyses conducted by an independent Data Monitoring Committee (DMC). The current predefined safety analyses occurred when 150pts received ≥ 1 cycle of tx. Results: As of Sep 16, 2011, 207 pts are included in this aggregate analysis: 50% male; median age, 63 yrs (range 36-83); ECOG PS 0/1, 50%/50%. Of the 207 pts, 204 pts received study tx, and 61 pts ended study tx. Most frequent adverse events (AE) are shown (table). Ten pts (5%) died during or within 30 days of the end of tx. Seven events were attributed to or associated with disease progression. One event of cardiac failure was reported to be possibly tx related. Pulmonary embolism was suspected but not confirmed. Conclusions: The GAMMA study continues per protocol. The only grade 3/4 AE occurring in more than 5% of patients to date is neutropenia. [Table: see text]

Results of a phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim (PEG) in patients (pts) receiving first-line FOLFOX or FOLFIRI and bevacizumab (B) for colorectal cancer (CRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. LBA445-LBA445 ◽  
Author(s):  
Tamas Pinter ◽  
Steve Abella ◽  
Alvydas Cesas ◽  
Adina Croitoru ◽  
Jochen Decaestecker ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Free Survival ◽  
Clinically Significant ◽  
Grade 3

LBA445 Background: The literature reports that adding biologics to chemotherapy (ctx) may increase the incidence of clinically significant neutropenia. This trial was conducted to evaluate the efficacy of PEG in reducing the incidence of febrile neutropenia (FN) in pts with locally advanced (LA) or metastatic (m)CRC receiving first-line treatment with either FOLFOX/B or FOLFIRI/B. Methods: Key eligibility: ≥ 18 years old; measurable, nonresectable CRC per RECIST 1.1. Pts were randomly assigned 1:1 to either placebo or 6 mg PEG ~24 h after ctx/B. The study treatment period included four Q2W cycles, but pts could continue their assigned regimen until progression. Pts were stratified by region (North America vs rest of world), stage (LA vs mCRC), and ctx (FOLFOX vs FOLFIRI). Estimated sample size (N = 800) was based on the expected incidence of grade 3/4 FN (primary endpoint) across the first 4 cycles of ctx/B, powered for PEG superiority over placebo. Other endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: 845 pts were randomized (Nov 2009 to Jan 2012) and received study treatment; 783 pts completed 4 cycles of ctx/B. Median age was 61 years; 512 (61%) pts were male; 819 (97%) had mCRC; 414 (49%) received FOLFOX, and 431 (51%) received FOLFIRI. Grade 3/4 FN (first 4 cycles) for placebo vs PEG was 5.7% vs 2.4%; OR 0.41; p = 0.014. A similar incidence of other ≥ grade 3 adverse events was seen in both arms (28% placebo; 27% PEG). See Table for additional results. Conclusions: PEG significantly reduced the incidence of grade 3/4 FN in this pt population receiving standard ctx/B for CRC. Follow-up is ongoing. Clinical trial information: NCT00911170. [Table: see text]

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