Copanlisib + rituximab versus rituximab + placebo in patients with relapsed follicular (FL) or marginal zone lymphoma (MZL): Subset analysis from the phase III CHRONOS-3 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7510-7510
Author(s):  
Matthew J. Matasar ◽  
Marcelo Capra ◽  
Muhit Özcan ◽  
Fangfang Lv ◽  
Wei Li ◽  
...  
Keyword(s):  
Disease Progression ◽  
Primary Endpoint ◽  
Response Rate ◽  
Pi3k Inhibitor ◽  
Phase Iii ◽  
Upper Respiratory Tract ◽  
Subset Analysis ◽  
Risk Of Disease ◽  
To Receive ◽  
Common Teaes

7510 Background: Rituximab (R) monotherapy is an approved treatment for patients (pts) with relapsed indolent NHL (iNHL) who have a prolonged progression-free and treatment-free interval after last R-based therapy or who are unwilling/unfit to receive chemotherapy. Copanlisib (C) is a PI3K inhibitor approved as monotherapy in pts with relapsed FL who have progressed after ≥2 systemic therapies. The recent Phase III CHRONOS-3 study in pts with relapsed iNHL treated with C+R vs placebo (P)+R (NCT02367040) met its primary endpoint with a significant 48% reduction in the risk of disease progression or death (Matasar et al. AACR 2021). We report here a pre-planned subset analysis in pts with relapsed FL or MZL. Methods: Pts with relapsed iNHL who were progression- and treatment-free for ≥12 months (mo) after last R-based therapy or ≥6 mo if unwilling/unfit to receive chemotherapy were randomized 2:1 to receive C+R or P+R. C 60 mg/P was given i.v. on days 1, 8, and 15 (28-day cycle); R 375 mg/m2 was given i.v. on days 1, 8, 15, and 22 of cycle 1 and on day 1 of cycles 3, 5, 7, and 9. Primary endpoint was centrally assessed progression-free survival (PFS) by Cheson 2014 criteria. Secondary endpoints included objective response rate (ORR), duration of response (DoR), complete response rate (CRR), time to progression (TTP), and treatment-emergent adverse events (TEAEs). All randomized pts were assessed for efficacy; pts were assessed for safety if they received ≥1 dose of C/P or R. The data cut-off date was August 31, 2020. Results: From a total dataset of 458 iNHL pts, 250 pts with FL/MZL (184 FL/66 MZL) were randomized to C+R and 120 (91 FL/29 MZL) to P+R. Median age was 62 years (range 28-91) and the arms were well balanced. With a median follow-up of 18.5 mo, C+R significantly reduced the risk of disease progression/death vs P+R (HR = 0.55 [95% CI 0.40, 0.76]; 1-sided p = 0.0001); median PFS was 22.2 mo (95% CI 19.1, 33.1) vs 15.4 mo (95% CI 11.0, 19.2), respectively. Median TTP was 27.5 mo for C+R vs 15.4 mo for P+R (HR = 0.500; 1-sided p = 0.00001). ORRs were 82.4% (CRR 37.6%) for C+R and 50.8% (CRR 18.3%) for P+R; median DoR was 23.9 mo vs 17.9 mo, respectively. Most common TEAEs (all grades [G]/G3+) in pts with FL/MZL receiving C+R (n = 249) were hyperglycemia (72.7%/59.0%), hypertension (53.8%/43.0% [all G3]), and diarrhea (35.3%/5.6% [all G3]). For pts receiving P+R (n = 116), the most common TEAEs were hyperglycemia (23.3%/7.8% [all G3]), hypertension (19.8%/8.6% [all G3]), neutropenia (18.1%/13.8%), and upper respiratory tract infection (18.1%/0%). Conclusions: C+R demonstrated superior efficacy vs P+R in pts with relapsed FL/MZL and had a manageable safety profile, consistent with C and R as monotherapy. Copanlisib is the first PI3K inhibitor to be safely combined with R in relapsed FL/MZL, representing a potential new therapeutic option. Clinical trial information: NCT02367040.

P136 Efficacy and safety of olokizumab in a phase III trial in patients with moderately to severely active RA inadequately controlled by TNF-α inhibitor therapy

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Eugen Feist ◽  
Saeed Fatenejad ◽  
Sergey Grishin ◽  
Elena Korneva ◽  
Michael Luggen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Primary Endpoint ◽  
Inhibitor Therapy ◽  
Phase Iii ◽  
Major Adverse Cardiovascular Events ◽  
Research Support ◽  
Acr20 Response ◽  
Phase Iii Trial ◽  
Tnf Α ◽  
To Receive

Abstract Background/Aims  Olokizumab (OKZ) is a new humanised monoclonal antibody targeting IL-6. Here we present the results of the phase III study of OKZ in anti-TNF-IR patients. Methods  Patients with moderately to severely active RA who had previously failed TNF inhibitors (ClinicalTrials.gov Identifier NCT02760433/CREDO3) were randomized in a 2:2:1 ratio to receive subcutaneous (SC) injections of OKZ 64 mg every 2 weeks (q2w), OKZ 64 mg once every 4 weeks (q4w) or placebo (PBO), plus MTX. At week 16, all subjects in the PBO group were randomized in a 1:1 ratio to receive either of OKZ regimes. The primary endpoint was ACR20 response at week 12. Results  368 subjects were randomised according to the protocol and 320 patients (87%) completed the 24-week treatment period. Baseline characteristics were comparable across arms. Both regimens of OKZ were significantly better in primary endpoint: ACR20 were 60.9% (p = 0.0029 in comparison vs. PBO) in OKZ q2w, 59.6% in OKZ q2w (p = 0.0040 in comparison vs. PBO) and 40.6% in PBO. The key efficacy outcomes were maintained throughout the 24-week period of the study. Overall incidences of treatment-emergent adverse events (TEAE) were 65.5% in OKZ q2w, 65.0% in OKZ q4w and 50.7% in PBO. Subsequent randomization of PBO arm at week 16 did not change TEAEs incidence rate per treatment group significantly: 64.3% in any OKZ q2w and 59.7% in any OKZ q4w. The majority of TEAEs in all groups were not serious and were of mild or moderate severity. Incidence of treatment-emergent serious adverse events (TESAE) were: 12 (7.0%) subjects in any OKZ q2w; 6 subjects (3.2%) in any OKZ q4w group, all in the first 16 weeks. The most frequently reported TESAEs across all treatment groups were infections and infestations: 2 (1.2%) in OKZ q2w group, 2 (1.1%) in OKZ q4w group. No opportunistic infections including active tuberculosis, major adverse cardiovascular events, gastrointestinal perforations or deaths were reported. Conclusion  In this global Phase III trial in patients with moderately to severely active RA inadequately controlled by TNF-α inhibitor therapy, treatment with OKZ plus MTX in both regimes (OKZ 64 mg q2w and OKZ 64 mg q4w) was associated with significant improvements in the signs and symptoms of RA compared to PBO plus MTX over a 24-week period. Treatment with OKZ q2w and q4w in this difficult to treat population was well tolerated and consistent with the established safety profile of anti-IL-6 agents. Disclosure  E. Feist: Consultancies; R-Pharm, Abbvie, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi. Honoraria; R-Pharm, Abbvie, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Member of speakers’ bureau; R-Pharm, Abbvie, AB2Bio, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Grants/research support; Lilly, Novartis, Pfizer, Roche/Chugai. S. Fatenejad: Consultancies; RPharm International. Shareholder/stock ownership; Pfizer. S. Grishin: Corporate appointments; Employed by R-Pharm. E. Korneva: Corporate appointments; Employed by R-Pharm. M. Luggen: Consultancies; Amgen, Sun Pharmaceuticals, R-Pharm International. Grants/research support; I havAbbvie, R-Pharm, Sun Pharmaceuticals, Pfizer, Novartis, Lilly, and GSK. E. Nasonov: Honoraria; Lilly, Abbnie, Prizer, Biocad, R-Pharm. Member of speakers’ bureau; Lilly, Abbnie, Prizer, Biocad, R-Pharm. M. Samsonov: Corporate appointments; Employed by R-Pharm.

scholarly journals Impact of early vs. delayed initiation of dutasteride/tamsulosin combination therapy on the risk of acute urinary retention or BPH-related surgery in LUTS/BPH patients with moderate-to-severe symptoms at risk of disease progression

2020 ◽  
Author(s):  
Salvatore D’Agate ◽  
Chandrashekhar Chavan ◽  
Michael Manyak ◽  
Juan Manuel Palacios-Moreno ◽  
Matthias Oelke ◽  
...  
Keyword(s):  
At Risk ◽  
Combination Therapy ◽  
Disease Progression ◽  
Urinary Retention ◽  
Acute Urinary Retention ◽  
Treatment Algorithm ◽  
Phase Iii ◽  
Rank Test ◽  
Survival Curves ◽  
Risk Of Disease

Abstract Purpose To evaluate the effect of delayed start of combination therapy (CT) with dutasteride 0.5 mg and tamsulosin 0.4 mg on the risk of acute urinary retention or benign prostatic hyperplasia (BPH)-related surgery (AUR/S) in patients with moderate-to-severe lower urinary tract symptoms (LUTS) at risk of disease progression. Methods Using a time-to-event model based on pooled data from 10,238 patients from Phase III/IV dutasteride trials, clinical trial simulations (CTS) were performed to assess the risk of AUR/S up to 48 months in moderate-to-severe LUTS/BPH patients following immediate and delayed start of CT for those not responding to tamsulosin monotherapy. Simulation scenarios (1300 subjects/arm) were investigated, including immediate start (reference) and alternative delayed start (six scenarios 1–24 months). AUR/S incidence was described by Kaplan–Meier survival curves and analysed using log-rank test. The cumulative incidence of events as well as the relative and attributable risks were summarised stratified by treatment. Results Survival curves for patients starting CT at month 1 and 3 did not differ from those who initiated CT immediately. By contrast, significant differences (p < 0.001) were observed when switch to CT occurs ≥ 6 months from the initial treatment. At month 48, AUR/S incidence was 4.6% vs 9.5%, 11.0% and 11.3% in patients receiving immediate CT vs. switchers after 6, 12 and 24 months, respectively. Conclusions Start of CT before month 6 appears to significantly reduce the risk of AUR/S compared with delayed start by ≥ 6 months. This has implications for the treatment algorithm for men with LUTS/BPH at risk of disease progression.

Randomized Phase III Study of Gemcitabine-Cisplatin Versus Etoposide-Cisplatin in the Treatment of Locally Advanced or Metastatic Non–Small-Cell Lung Cancer

1999 ◽  
Vol 17 (1) ◽  
pp. 12-12 ◽  
Author(s):  
Felipe Cardenal ◽  
M. Paz López-Cabrerizo ◽  
Antonio Antón ◽  
Vicente Alberola ◽  
Bartomeu Massuti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE: We conducted a randomized trial to compare gemcitabine-cisplatin with etoposide-cisplatin in the treatment of patients with advanced non–small-cell lung cancer (NSCLC). The primary end point of the comparison was response rate. PATIENTS AND METHODS: A total of 135 chemotherapy-naive patients with advanced NSCLC were randomized to receive either gemcitabine 1,250 mg/m2 intravenously (IV) days 1 and 8 or etoposide 100 mg/m2 IV days 1 to 3 along with cisplatin 100 mg/m2 IV day 1. Both treatments were administered in 21-day cycles. One hundred thirty-three patients were included in the intent-to-treat analysis of response. RESULTS: The response rate (externally validated) for patients given gemcitabine-cisplatin was superior to that for patients given etoposide-cisplatin (40.6% v 21.9%; P = .02). This superior response rate was associated with a significant delay in time to disease progression (6.9 months v 4.3 months; P = .01) without an impairment in quality of life (QOL). There was no statistically significant difference in survival time between both arms (8.7 months for gemcitabine-cisplatin v 7.2 months for etoposide-cisplatin; P = .18). The overall toxicity profile for both combinations of drugs was similar. Nausea and vomiting were reported more frequently in the gemcitabine arm than in the etoposide arm. However, the difference was not significant. Gemcitabine-cisplatin produced less grade 3 alopecia (13% v 51%) and less grade 4 neutropenia (28% v 56% ) but more grade 3 and 4 thrombocytopenia (56% v 13%) than did etoposide-cisplatin. However, there were no thrombocytopenia-related complications in the gemcitabine arm. CONCLUSION: Compared with etoposide-cisplatin, gemcitabine-cisplatin provides a significantly higher response rate and a delay in disease progression without impairing QOL in patients with advanced NSCLC.

Updated safety results from EXIST-2: Everolimus therapy for angiomyolipoma (AML) associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (sLAM).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4632-4632
Author(s):  
John Bissler ◽  
Christopher Kingswood ◽  
B. A. Zonnenberg ◽  
Michael Frost ◽  
Elena Belousova ◽  
...  
Keyword(s):  
Data Analysis ◽  
Disease Progression ◽  
Response Rate ◽  
Safety Data ◽  
Study Drug ◽  
Double Blind Study ◽  
Double Blind ◽  
Initial Analysis ◽  
Response Status ◽  
To Receive

4632 Background: EXIST-2 (NCT00790400) is a randomized, double-blind, placebo-controlled, phase 3 trial assessing the efficacy and safety of everolimus, an oral mTOR inhibitor, for treating AML in patients with TSC or sLAM. We have previously reported that everolimus resulted in a significantly higher AML response rate vs placebo (41.8% vs 0%; 95% CI: 23.5–58.4; p<0.0001) with a consistent safety profile (Bissler et al. J Am Soc Nephrol. 22, 2011, Abstract LB-PO3159). Here we present a 90-day safety update. Methods: 118 eligible patients were randomized 2:1 to receive everolimus 10 mg daily (n=79) or placebo (n=39). The primary efficacy endpoint was AML response rate (proportion of patients with best overall AML response status of “response”). Original cut-off date for data analysis was 30 Jun 2011. An updated analysis of the safety data for the safety set (all patients receiving ≥1 dose of double-blind study drug with a valid post-baseline assessment) to 14 Oct 2011 are presented here. Results: As of 14 Oct 2011, median treatment duration was 48.1 and 45.0 weeks for everolimus and placebo arms, respectively. Discontinuations in the double-blind period were the same in the everolimus arm as the initial analysis, but had increased by 4 patients in the placebo arm since initial analysis (3 due to disease progression, 1 withdrew consent). The majority of adverse events (AEs) continued to be grade 1 or 2; the incidence of serious AEs was slightly higher than initially reported, particularly in the placebo arm (everolimus 20.3%, placebo 23.1%). AE incidence leading to discontinuation was the same as initially reported (everolimus 3.8%, placebo 10.3%). In the updated data, 3 additional everolimus patients required dose interruption or reduction due to AEs; dose reduction/interruption remained more common in the everolimus arm (51.9% vs. 20.5%). Conclusions: Overall, the 90-day updated safety data analysis from the EXIST-2 trial has not revealed any additional safety concerns. No other patients receiving everolimus withdrew for any reason, whereas 3 more patients receiving placebo withdrew due to disease progression.

REVEL: A randomized, double-blind, phase III study of docetaxel (DOC) and ramucirumab (RAM; IMC-1121B) versus DOC and placebo (PL) in the second-line treatment of stage IV non-small cell lung cancer (NSCLC) following disease progression after one prior platinum-based therapy.

2014 ◽  
Vol 32 (18_suppl) ◽  
pp. LBA8006-LBA8006 ◽  
Author(s):  
Maurice Perol ◽  
Tudor-Eliade Ciuleanu ◽  
Oscar Arrieta ◽  
Kumar Prabhash ◽  
Konstantinos N. Syrigos ◽  
...  
Keyword(s):  
Disease Progression ◽  
Primary Endpoint ◽  
Objective Response ◽  
Pulmonary Hemorrhage ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Double Blind

LBA8006^ Background: RAM is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. The REVEL study evaluated the efficacy and safety of RAM+DOC vs. PL+DOC (DOC) in patients (pts) with stage IV nonsquamous (NSQ) and squamous (SQ) NSCLC after platinum-based therapy. Methods: Pts with NSQ and SQ stage IV NSCLC were randomized 1:1 (stratified by sex, region, ECOG PS, and prior maintenance therapy) to receive DOC 75 mg/m2 in combination with either RAM 10 mg/kg or PL on day 1 of a 21-day cycle until disease progression, unacceptable toxicity, or death. The primary endpoint was overall survival (OS). Secondary efficacy endpoints included progression-free survival (PFS), and objective response rate (ORR). Results: Between Dec 2010 and Feb 2013, 1,253 pts (26.2% SQ) were randomized (RAM+DOC: 628; DOC: 625). Pt characteristics were balanced between arms. ORR was 22.9% for RAM+DOC and 13.6% for DOC (P<0.001). The hazard ratio (HR) for PFS was 0.762 (P<0.0001); median PFS was 4.5 months (m) for RAM+DOC vs. 3.0m for DOC. REVEL met its primary endpoint; the OS HR was 0.857 (95% CI 0.751, 0.98; P=0.0235); median OS was 10.5m for RAM+DOC vs. 9.1m for DOC. OS was longer for RAM+DOC in most pt subgroups, including SQ and NSQ histology. Grade ≥3 adverse events (AEs) occurring in >5% of pts on RAM+DOC were neutropenia (34.9% vs. 28.0%), febrile neutropenia (15.9% vs. 10.0%), fatigue (11.3% vs. 8.1%), leukopenia (8.5% vs. 7.6%), hypertension (5.4% vs. 1.9%), and pneumonia (5.1% vs. 5.8%). Grade 5 AEs were comparable between arms (5.4% vs. 5.8%), as was pulmonary hemorrhage (any grade; all pts: 2.1% vs. 1.6%; SQ pts: 3.8% vs. 2.4%). Conclusions: REVEL demonstrated a statistically significant improvement in ORR, PFS, and OS for RAM+DOC vs DOC in NSCLC pts with stage IV NSCLC as second-line treatment after platinum-based therapy. Benefits were similar in NSQ and SQ pts, and no unexpected AEs were identified. Clinical trial information: NCT01168973.

IMPALA, a randomized phase III study in patients with metastatic colorectal carcinoma: Immunomodulatory maintenance therapy with TLR-9 agonist MGN1703.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. TPS791-TPS791 ◽  
Author(s):  
David Cunningham ◽  
Alfredo Zurlo ◽  
Ramon Salazar ◽  
Michel Ducreux ◽  
Tom Samuel Waddell ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Immune Cell ◽  
Cox Regression ◽  
Objective Response ◽  
Phase Iii ◽  
Induction Treatment ◽  
Self Administration ◽  
Open Label ◽  
Response To Chemotherapy ◽  
To Receive

TPS791 Background: The potent TLR-9 agonist MGN1703, a synthetic DNA-based immunomodulator, was compared to placebo in metastatic colorectal cancer (mCRC) patients with disease control after standard induction chemotherapy +/- bevacizumab in the phase II IMPACT trial and showed a superior effect with a hazard ratio for the primary endpoint PFS on maintenance of 0.55 (p=0.041) by local investigator assessment and 0.56 (p=0.070) by independent radiological review. In the MGN1703 arm 3 objective responses were observed, two of them appearing as late as 9 months after the start of treatment. At time of study closure 4 MGN1703 patients were still without progressive disease and continued treatment by self-administration in a compassionate use setting. Exploratory Cox regression and ROC analyses suggested a potential predictive role at baseline for normal CEA, objective response to prior chemotherapy and presence of activated NKT-cells. Methods: The pivotal IMPALA study has been designed to confirm these data and started to enroll patients with smaller tumor burden after a good response to chemotherapy, as best candidates to receive a maintenance treatment with immunotherapy. IMPALA is a randomized, international, multicenter, open-label phase III trial that will include 540 patients from 120 centers with the collaboration of the AIO, TTD, and GERCOR cooperative groups and is currently recruiting patients. In this study mCRC patients with an objective tumor response following any first line induction therapy will be randomized to MGN1703 monotherapy maintenance or local standard of care. At time of relapse, patients will reintroduce the induction treatment whenever feasible, with those in the experimental arm continuing to receive MGN1703 in the weeks without chemotherapy. Patients will also be stratified by CEA level and activated NKT at baseline. The primary endpoint of the study will be overall survival. Secondary endpoints include PFS, response rates, safety, and QoL in selected centers. All patients will be evaluated for cytokines and chemokines in serum and the activation status of various immune cell populations. Clinical trial information: NCT02077868.

Immunomodulatory switch maintenance therapy in metastatic colorectal carcinoma: The phase III IMPALA study.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS785-TPS785 ◽  
Author(s):  
David Cunningham ◽  
Werner Scheithauer ◽  
Alfredo Zurlo ◽  
Ramon Salazar ◽  
Michel Ducreux ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Primary Endpoint ◽  
Immune Cell ◽  
Immune Monitoring ◽  
Phase Iii ◽  
Induction Treatment ◽  
Impact Study ◽  
Open Label ◽  
Double Blind ◽  
To Receive

TPS785 Background: The Toll-like receptor 9 agonist MGN1703 was compared to placebo in 59 metastatic CRC (mCRC) patients with disease control after standard induction chemotherapy in the double-blind randomized phase 2 IMPACT study. MGN1703 showed a superior effect over placebo, with a hazard ratio (HR) for the primary endpoint “PFS on maintenance” of 0.55 (p = 0.041) by local assessment and 0.56 (p = 0.070) by independent radiological review. Exploratory PFS analyses identified patients with objective RECIST response, normalized CEA and presence of activated NKT cells at the end of induction treatment to benefit the most from MGN1703. The OS evaluation showed a HR of 0.40 (median 24.5 vs. 15.1 months) for patients with RECIST response after induction therapy. Furthermore, at time of IMPACT study closure, 4 MGN1703 patients were still without progressive disease and continued treatment in compassionate use. As of August 2015, 3 patients were still receiving MGN1703 treatment in excess of three years (47-55 months), with 2 objective responses ongoing over 46 months. Methods: The international, multicenter, open-label phase 3 IMPALA study is conducted in collaboration with the AIO, TTD and GERCOR cooperative groups. In IMPALA, mCRC patients having achieved an objective tumor response following any type of first line induction therapy are randomized to receive MGN1703 switch maintenance monotherapy in the experimental arm or local standard of care in the control arm. In case of relapse, patients will reintroduce induction treatment whenever feasible, with those in the experimental arm continuing to receive MGN1703 therapy in the weeks without infusional chemotherapy. The primary endpoint of the study will be OS. Secondary endpoints include PFS, response rates, safety, and QoL in selected centers. Induction treatment, CEA and activated NKT at baseline are stratification factors and will be prospectively assessed. All randomized patients take part in a comprehensive immune monitoring plan evaluating cytokines and chemokines in serum and the activation status of immune cell populations. Recruitment started in September 2014 and the study is expected to recruit 540 patients within 24 months in 8 European countries. Clinical trial information: NCT02077868.

An EORTC Gastrointestinal Group phase III evaluation of combinations of methyl-CCNU, 5-fluorouracil, and adriamycin in advanced gastric cancer.

1987 ◽  
Vol 5 (9) ◽  
pp. 1387-1393 ◽  
Author(s):  
A Lacave ◽  
J Wils ◽  
H Bleiberg ◽  
E Diaz-Rubio ◽  
N Duez ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Response Rate ◽  
Multicenter Trial ◽  
Phase Iii ◽  
Rank Test ◽  
Short Survival ◽  
Log Rank Test ◽  
Prospective Phase ◽  
To Receive

In a prospective phase III multicenter trial, 189 patients with advanced measurable and nonmeasurable gastric cancer were randomized to receive 5-fluorouracil (5-FU) combined with Adriamycin (FA) or FA plus methyl-CCNU (MeFA). The response rate in patients with measurable disease was 10% (three of 29), and 18% (five of 28), respectively. No difference in the duration of survival was detected (P = .14; log rank test). Median survivals were 21 and 32 weeks, respectively. Toxicity was moderate, but there have been two toxic deaths among the patients who received FA. Because of the low response rate and the short survival, neither regimen can be recommended for the treatment of advanced gastric cancer.

A phase III, randomized, double-blind, multicenter trial comparing the investigational agent orteronel (TAK-700) plus prednisone (P) with placebo plus P in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or following docetaxel-based therapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4693-TPS4693 ◽  
Author(s):  
Robert Dreicer ◽  
David B. Agus ◽  
Joaquim Bellmunt ◽  
Johann Sebastian De Bono ◽  
Daniel Peter Petrylak ◽  
...  
Keyword(s):  
Disease Progression ◽  
Fusion Gene ◽  
Phase 1 ◽  
Objective Response ◽  
Specific Antigen ◽  
Phase Iii ◽  
Double Blind ◽  
Investigational Agent ◽  
Patient Reported ◽  
To Receive

TPS4693 Background: The investigational agent orteronel is a selective inhibitor of 17,20-lyase, a key enzyme in the testosterone synthesis pathway. In a phase 1/2 study in men with mCRPC, orteronel reduced prostate-specific antigen (PSA) levels, and inhibited testosterone and DHEA-S consistent with potent 17,20-lyase inhibition (Agus D, et al. J Clin Oncol 2012;30:s5 abst 98). Docetaxel-based chemotherapy is an effective but noncurative therapy for mCRPC that has progressed on hormonal therapy; new therapeutic options are needed. Methods: This double-blind, multicenter study is assessing orteronel + P vs placebo + P in men with mCRPC (NCT01193257; C21005). Patients must have evidence of disease progression during or after receiving a total of ≥360 mg/m2 docetaxel within a 6-mo period. Patients who are clearly intolerant to docetaxel or have progressive disease before receiving ≥360 mg/m2 are also eligible if they have received at least 225 mg/m2 of docetaxel within a 6-mo period and meet the other inclusion criteria. Other eligibility criteria include radiographically documented metastatic disease and baseline testosterone <50 ng/dL following surgical or medical castration. Prior adrenal-targeted therapies are not permitted. Men may have opioid-requiring bone pain. The planned sample size is 1083; men will be randomized 2:1 to receive orteronel 400 mg twice daily (BID) plus P 5 mg BID or placebo plus P. The primary endpoint is overall survival; other endpoints are radiographic progression-free survival, PSA decrease of ≥50% at 12 wks, pain response at 12 wks, safety, time to PSA progression, objective response by RECIST, circulating tumor cell and endocrine marker changes, and patient-reported outcomes. After disease progression, men may continue to receive study drug. Tumor specimens will be analyzed for biomarkers that may predict orteronel antitumor activity, including the TMPRSS2:ERG fusion gene. The same regimens are being evaluated in a concurrent phase 3 study in chemotherapy-naïve men with mCRPC (NCT01193244).

RAINBOW: A global, phase III, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastroesophageal junction (GEJ) and gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy rainbow IMCL CP12-0922 (I4T-IE-JVBE).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. LBA7-LBA7 ◽  
Author(s):  
Hansjochen Wilke ◽  
Eric Van Cutsem ◽  
Sang Cheul Oh ◽  
Gyorgy Bodoky ◽  
Yasuhiro Shimada ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Febrile Neutropenia ◽  
Disease Progression ◽  
Gastric Adenocarcinoma ◽  
Primary Endpoint ◽  
Phase Iii ◽  
Double Blind Study ◽  
Vegf Receptor ◽  
First Line ◽  
Double Blind

LBA7 Background: RAM is a human IgG1 monoclonal antibody VEGF-receptor 2 antagonist. We conducted a global, placebo-controlled, double-blind, phase III trial to evaluate the efficacy and safety of PTX +/- RAM in patients with metastatic GEJ or gastric adenocarcinoma who had disease progression on or within 4 months after first-line platinum- and fluoropyrimidine-based combination therapy. Methods: Pts received RAM (8 mg/kg IV q2w) or placebo (PL) plus PTX (80 mg/m2 d1, 8, 15 of a 4 week cycle) until disease progression, unacceptable toxicity, or death. Eligible pts had ECOG PS ≤ 1; and adequate organ function. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), time to progression (TTP), and safety. Results: From Dec 2010 to Sep 2012, 665 pts were randomized (RAM+PTX: 330; PTX: 335). Baseline characteristics were generally balanced between arms. The OS hazard ratio (HR) was 0.807 (95% CI 0.678, 0.962; p=0.0169). Median OS was 9.63m for RAM+PTX and 7.36m for PTX. The HR for PFS was 0.635 (95% CI 0.536, 0.752; p <0.0001). Median PFS was 4.40m and 2.86m. Median TTP was 5.5m RAM+PTX; 3.0m PTX (p <0.0001). ORR was 28% RAM+PTX;16% PTX (p=0.0001). Grade ≥ 3 adverse events (AEs) occurring in >5% of patients on RAM+PTX were: neutropenia (40.7% RAM+PTX;18.8% PTX), leukopenia (17.4% vs 6.7% ), hypertension (14.1% vs 2.4%), anemia (9.2% vs 10.3%), fatigue (7.0% vs 4.0%), abdominal pain (5.5% vs 3.3%), and asthenia (5.5% vs 3.3%). Febrile neutropenia was reported in 3.1% RAM+PTX; 2.4% PTX. Conclusions: The primary endpoint of improved OS was met. A statistically significant and clinically meaningful OS benefit of > 2 months was observed for RAM+PTX vs. PTX in gastric and GEJ cancer after progression on 1st-line therapy, as were significant benefits in PFS and ORR. Neutropenia was more frequently reported in the RAM+PTX arm but incidence of febrile neutropenia was comparable between arms. Clinical trial information: NCT01170663.

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