Irinotecan versus best supportive care (BSC) as second-line therapy in gastric cancer: A randomized phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4540-4540 ◽  
Author(s):  
P. C. Thuss-Patience ◽  
A. Kretzschmar ◽  
T. Deist ◽  
A. Hinke ◽  
D. Bichev ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Phase Iii ◽  
Open Label ◽  
Logrank Test ◽  
Line Therapy ◽  
Phase Iii Study ◽  
Ecog Ps ◽  
Line Chemotherapy

4540 Background: Up to now the value of 2nd-line therapy for metastatic gastric cancer is unclear. So far there are no randomized phase III data comparing 2nd-line chemotherapy to BSC. Irinotecan has proven activity in 1st-line therapy. In this randomized phase III study we compared irinotecan to BSC to evaluate the value of 2nd- line chemotherapy for gastric cancer. Methods: Prospective multicenter randomized phase III study, open label. Eligibility: Metastatic or locally advanced gastro-esophageal junction or gastric adenocarcinoma. Objective tumor progession (PD) within 6 months after 1st- line chemotherapy. ECOG PS 0–2. Statistics: Primary endpoint: Overall survival (OS). Hypothesis: H1: OS(Irinotecan)>OS(BSC). Calculated number of pts needed (power 80%, alpha error 5%): 60 pts per arm. Stratification for a) PD less versus (vs) more than 3 months after 1st line chemotherapy, b) ECOG PS 0/1 vs 2. Treatment: Arm A: Irinotecan 250mg/m2 q3w (1st cycle) to be increased to 350 mg/m2, depending on toxicity. Arm B: BSC Results: Between Oct 2002 and Dec 2006 40 pts were randomized. The study was closed prematurely due to poor accrual. Arm A:21 pts, arm B 19 pts. Median age A: 58 yrs (43–73), B: 55 yrs (35–72); PD less vs more than 3 months after 1st-line chemotherapy: A: 18 / 3, B: 17 / 2pts. ECOG PS 0/1 vs 2: A: 17/ 4, B: 14/ 5pts. Pre-treatment with cisplatin: A: 21, B:19 pts. Arm A: 68 cycles administered in 21 pts. Toxicity: (main CTC grade 3/ 4): Nausea 1 pt, vomiting 1 pt, diarrhoea: 5 pts, neutropenic fever: 2 pts, data incomplete 6 pts. In 37% of 19 evaluable pts irinotecan dose was escalated to 350mg/m2. Response (19 pts evaluable): No objective responses, SD 58%, PD 42%. Improvement of tumor related symptoms: 44% of pts in arm A, 5% in arm B. Survival: (evaluable pts arm A 21, arm B 18): median survival arm A: 123 days (95%CI 95–216), arm B 72.5 days (95%CI 41–106); OS: HR=2.85 (95%CI 1.41–5.79), Logrank test (two-sided): p=0.0027. Conclusions: To our knowledge this is the first randomized phase III study investigating 2nd- line chemotherapy in gastric cancer. Irinotecan as 2nd-line chemotherapy significantly prolongs overall survival compared to BSC. 2nd-line chemotherapy can now be considered as a proven option in gastric cancer. [Table: see text]

A single-arm multicenter phase II trial of doxorubicin (Doxo) in combination with trabectedin (Trab) given as first-line treatment to patients with metastatic/advanced uterine (U-LMS) and soft tissue leiomyosarcoma (ST-LMS): Final results of the LMS-02 study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11506-11506
Author(s):  
Patricia Pautier ◽  
Anne Floquet ◽  
Christine Chevreau ◽  
Nicolas Penel ◽  
Cecile Guillemet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Residual Disease ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Response Duration ◽  
Phase Iii ◽  
Line Therapy ◽  
Phase Iii Study ◽  
Line Setting

11506 Background: U-LMS and ST-LMS are rare tumors with poor prognosis when locally advanced or metastatic, and with moderate chemosensitivity. Overall response rates (ORR) given in the 1st-line setting do not exceed 50% for U-LMS and 35% for ST-LMS with a mean response duration of 3- 6 months without impact on overall survival (OS). In 2015 we reported very encouraging results of the LMS-02 study (NCT02131480) with ORR of 59.6% in U-LMS, and 39.3% in ST-LMS with manageable toxicity (Pautier; Lancet oncol 2015). Herein, we report the updated results of progression-free survival (PFS) and final results of overall survival (OS). Methods: Patients (pts) received 60 mg/m² intravenous Doxo followed by trabectedin 1.1 mg/m2 as a 3-hour infusion on Day 1 and pegfilgrastim on Day 2, repeated every 3 weeks for up to 6 cycles. Surgery for residual disease was permitted. Patients were stratified into U-LMS and ST-LMS groups. Results: Overall, 108 patients with LMS with a median age of 59 years and mostly metastatic disease (85%) were enrolled. Of those, 77 patients (71.3%) have received all 6 cycles of treatment, and 20 patients (18.5%) had metastasis resection. With a median follow-up of 7.2 years (95% CI: 6.9 - 8.2), the overall median PFS was 10.1 months (95% CI: 8.5 - 12.6), being 8.3 months (95 CI: 7.4 - 10.3) and 12.9 months (95% CI: 9.2 - 14.1) in U and ST group, respectively. Median OS was 34.4 months (95% CI: 26.9 - 42.7), being 27.5 months (95% CI: 17.9 - 38.2) in U-LMS and 38.7 months (95% CI: 31.0 - 52.9) in ST-LMS group. The median OS among the 20 pts with surgery was not reached vs 31.6 months in the population without surgery (95% IC: 23.9 - 35.4). Conclusions: The Doxo +Trab combination is an effective 1st-line therapy for pts with LMS, with promising PFS and OS results and an acceptable safety profile. Merely for comparison, the most recent results of Doxo alone in metastatic LMS, given in 1st-line setting in a phase III ANNOUNCE trial conducted during the same period, reported median PFS of 6.9 months, and median OS of 21.9 months (ASCO 2019 LBA3). Results of the LMS04 trial (NCT02997358), a randomized phase III study comparing this combination vs Doxo alone in 1st-line therapy in metastatic LMS are pending. Clinical trial information: NCT02131480 .

scholarly journals Adjuvant albumin-bound paclitaxel combined with S-1 vs. oxaliplatin combined with capecitabine after D2 gastrectomy in patients with stage III gastric adenocarcinoma: a phase III multicenter, open-label, randomized controlled clinical trial protocol

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiangdong Cheng ◽  
Dan Wu ◽  
Nong Xu ◽  
Luchuan Chen ◽  
Zhilong Yan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Clinical Study ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Phase Iii ◽  
Stage Iii ◽  
Open Label ◽  
D2 Gastrectomy

Abstract Background Surgery is the only treatment option for operable gastric cancer. The CLASSIC and ACTS-GC studies showed that the 5-year overall survival (OS) of patients with stage III gastric cancer undergoing D2 gastrectomy is still very low. Whether adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) combined chemotherapy is more effective than the XELOX standard adjuvant chemotherapy in patients with stage III gastric cancer has not been confirmed. Methods This is a multicenter, open-label, phase III clinical study. In this trial, 616 patients with locally advanced stage III gastric cancer that underwent curative D2 radical surgery and achieved R0 are planned to be included. Patients will be randomized 1:1 to nab-paclitaxel combined with S-1 (AS) vs. oxaliplatin combined with capecitabine (XELOX). XELOX group: Patients assigned to the XELOX group received eight 3-week cycles of oral capecitabine (1000 mg/m2) twice daily on days 1–14 of each cycle plus intravenous oxaliplatin 130 mg/m2 on day 1 of each cycle. AS group: AS group received eight 3-week cycles of oral S-1 (80–120 mg) (< 1.25 m2, 40 mg; 1.25 to < 1.5 m2, 50 mg; and > 1.5 m2, 60 mg) twice daily on days 1–14 plus intravenous nab-paclitaxel 120 mg/m2 on days 1 and 8 of each cycle. The primary endpoint was the 3-year disease-free survival (3-year-DFS) defined as the time from randomisation to the time of recurrence of the original gastric cancer, development of a new gastric cancer, or death from any cause. The secondary endpoints were the overall survival, (defined as the time from the date of randomisation to date of death from any cause) and safety (any adverse event). Discussion Compared with previous studies, this study includes nab-paclitaxel based on S-1 adjuvant chemotherapy, which is expected to achieve better efficacy and lower toxicity than the standard treatment. This study is the first clinical study to evaluate the safety and efficacy of nab-paclitaxel combined with S-1 in patients with stage III gastric cancer after D2 radical resection. Trial registration This clinical trial has been registered with ClinicalTrials.gov, registration number: NCT04135781, on October 20th, 2019.

CS1001-304: A phase III study of fluorouracil and cisplatin (FP) with CS1001, an anti-PD-L1 antibody, or placebo in unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS255-TPS255
Author(s):  
Jin Li ◽  
Yuxian Bai ◽  
Qingshan Li ◽  
YouEn Lin ◽  
Hao Jiang ◽  
...  
Keyword(s):  
Safety Profile ◽  
Tumor Therapy ◽  
Locally Advanced ◽  
Phase Iii ◽  
Transgenic Rat ◽  
First Line ◽  
Multiple Tumor ◽  
Platinum Based Chemotherapy ◽  
Phase Iii Study ◽  
Ecog Ps

TPS255 Background: ESCC is the predominant histological subtype of esophageal cancer, particularly in Asian countries. Platinum-based chemotherapy is the first-line standard therapy for patients with unresectable, locally advanced, recurrent or metastatic ESCC. The FP regimen is recommended as the preferred treatment by guidelines. However, the survival benefit conferred by this therapy leaves considerable space for improvement, with median OS being less than 1 year. Blockade of the immune checkpoint receptors has shown clinical benefits in multiple tumor types. Recent studies combining standard treatments with checkpoint inhibitors have shown encouraging efficacy and favorable safety profile in patients with unresectable, locally advanced, recurrent or metastatic ESCC. CS1001 (sugemalimab) is the first full-length, fully human immunoglobin G4 (IgG4, s228p) anti-programmed death-ligand 1 (PD-L1) monoclonal antibody developed by the OMT transgenic rat platform. In an ongoing Phase Ib trial, CS1001 in combination with FP regimen demonstrated an ORR of 67.6% (25/37) and an mPFS of 9.0 months with a manageable safety profile in unresectable, locally advanced or distantly metastatic ESCC (19 Feb 2020 data cutoff; Shen, L., et al, ESMO 2020). Methods: CS1001-304 is a randomized, double-blind Phase III study to compare the efficacy and safety of FP regimen with CS1001 or placebo as first-line treatment in ESCC. The study enrolls patients with histologically or cytologically confirmed unresectable locally advanced, recurrent or metastatic ESCC who have ECOG PS of 0-1, patients are not eligible for curative therapy (curative surgery or definitive chemoradiotherapy), and have not received any prior systemic anti-tumor therapy for locally advanced or metastatic disease. Approximately 540 patients will be randomized at 2:1 into CS1001 + FP and placebo + FP arms respectively, stratified by PD-L1 expression status (PD-L1 expression < 1% vs ≥ 1% and < 10% vs ≥10%), ECOG PS (0 vs 1) and distant metastasis (no vs yes). Patients randomized to either arm will receive FP regimen (fluorouracil: 800 mg/m2/day, continuous intravenous infusion [IV], D1-4 of each cycle; cisplatin: 80 mg/m2, IV, D1 of each cycle), Q3W for up to 6 cycles in combination with CS1001 1200 mg or placebo (IV, D1 of each cycle), Q3W for up to 24 months. AEs will be monitored throughout the study and graded per NCI CTCAE v5.0. Tumor response will be assessed by RECIST v1.1 every 6 weeks in the first 12 months, and every 12 weeks thereafter. The primary endpoints are blinded independent central review (BICR)-assessed PFS and OS. Secondary endpoints include investigator-assessed PFS, BICR and investigator-assessed ORR and DoR, safety, PK profile, and immunogenicity. The study is actively enrolling patients in over 60 sites in China. Clinical trial information: NCT04187352.

A single-arm, open-label, U.S. expanded access study of vemurafenib in patients with metastatic melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8567-8567
Author(s):  
Lynn Mara Schuchter ◽  
Lawrence E. Flaherty ◽  
Omid Hamid ◽  
Gerald P. Linette ◽  
Sigrun Hallmeyer ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Response Rate ◽  
Phase Iii ◽  
Open Label ◽  
Expanded Access ◽  
Treatment Naïve ◽  
Phase Iii Study ◽  
Prior Systemic Therapy ◽  
Ecog Ps

8567 Background: Vemurafenib (vem) has been FDA approved for the treatment of unresectable or metastatic BRAFV600E mutated melanoma since August 2011 based on results of a randomized phase III study (treatment-naive) and a single arm phase II study (previously treated). We report results of an expanded access study that allowed appropriate patients (pts) to receive vem until the drug was approved. Methods: Eligible pts had metastatic melanoma with a BRAFV600E mutation as detected by the cobas 4800 BRAFV600 Mutation Test. Enrolled pts received oral vem 960 mg b.i.d. Adverse events (AEs) were evaluated for vem-related toxicities; tumor responses were assessed using RECIST 1.1. Results: 29 US sites screened 745 pts and enrolled 374 from December 2010 until October 2011. The following results are based on a median follow up time and treatment duration of 2 months. At baseline, mean age of pts was 54 y with 22% of pts ≥65 y; 75% had stage M1c disease; 29% had received radiotherapy for brain metastases. 19% of pts were ECOG PS 2 or 3; 71% of pts had prior systemic therapy for metastatic melanoma (21% 1 regimen; 50% ≥2 regimens). 50 pts had prior adjuvant treatment. At data cut-off, 243 pts had sufficient follow-up time for tumor assessment. In this group, the unconfirmed overall response rate was 52% (95% CI, 46 to 59). The median time to response was 1.8 months. Based on 240 pts with available ECOG PS status at time of analysis, response rate was 53% for pts with ECOG PS 0 or 1 (n=209), and 45% for pts with ECOG PS 2 or 3 (n=31). 370 pts were evaluable for safety analysis. The most common vem-related AEs were rash (36%), arthralgia (33%) and fatigue (21%) with the majority (~90%) of grade 1 or 2. 25 vem-related serious AEs were reported in 5.4% of pts with a slightly higher rate of pts with ECOG PS 2 or 3 (8.7%) compared to ECOG PS 0 or 1 (4.7%). 18% of pts missed at least one dose and 11% of pts required dose reduction of at least one level due to AEs. Conclusions: This expanded access study, with its limited follow-up time, confirms the established rapid and high tumor response rate with vem. No new safety signals were detected. Compared to the overall population, pts with an ECOG PS 2 or 3 demonstrated a similar benefit.

Randomized, phase III study of carboplatin plus paclitaxel for 8 cycles (CP8) versus carboplatin x 8 cycles plus paclitaxel x 4 cycles (C8P4) in advanced ovarian, fallopian, or primary peritoneal carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5033-5033
Author(s):  
Aristotelis Bamias ◽  
Eleni Timotheadou ◽  
Gerasimos Aravantinos ◽  
Dimitrios G. Pectasides ◽  
Christos A. Papadimitriou ◽  
...  
Keyword(s):  
Residual Disease ◽  
Randomized Study ◽  
Tumor Grade ◽  
Phase Iii ◽  
Lower Grade ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps ◽  
Line Chemotherapy

5033 Background: The combination of carboplatin/paclitaxel represents the standard 1st-line chemotherapy in advanced OC, FC, and PPC. The optimal duration of paclitaxel treatment has not been defined, while its use is associated with cumulative neurotoxicity in about 50% of patients, which becomes long-term in 15-20% of cases. We, therefore, designed a randomized study to investigate the effect of administering 4 instead of 8 cycles of paclitaxel in the combination carboplatin/paclitaxel on efficacy and tolerability of this treatment. Methods: Patients with FIGO stages IIC-IV OC, FC, PPC were included. Carboplatin AUC 6 and paclitaxel at 175 mg/m2 were used. Both agents were administered for 8 cycles in the CP8 arm, while paclitaxel was administered only for 4 cycles in the C8P4. The study was powered to detect a ± 15% difference in survival rate to a baseline rate of 50 % at the 3-year time point. Results: 389 pts were randomized (2/2004-1/2008) and 380 were eligible for analysis (CP8: 192, C8P4:188). The distribution (CP8 vs C8P4) of baseline characteristics were: stage III: 78% vs. 76%; IV: 12% vs. 15%, residual disease 0 cm: 25% vs. 22%, ECOG PS 0: 68% vs. 64%, serous carcinomas: 79% vs. 68%, tumor grade III: 56% vs. 63%. During a median follow up of 72.3 months 231 patients (111 [58%] in CP8 arm and 120 [64%] in the C8P4 arm) have died. Median PFS was significantly shorter in the C8P4 arm (21.41 vs. 16.46 months, HR [95% CI]: 1.36 [1.07-1.71], Wald’s p=0.011), while OS was similar between the two arms (53.41 vs. 46.59 months, HR [95% CI]: 1.18 [0.91-1.53], Wald’s p=0.211). Lower grade 3 or 4 neurotoxicity (1.9% vs. 10.8%, p< 0.001) but higher myelotoxicity (neutropenia 38.8% vs. 28.8%, p=0.031; thrombocytopenia 20% vs. 8.3%, p=0.004) was observed in the C8P4 arm. Conclusions: Lowering the total number of cycles of paclitaxel in 1st-line chemotherapy of advanced OC, FC, PPC resulted in similar OS but shorter median PFS and is not recommended in this setting. The reduction of neurotoxicity by limiting the total paclitaxel cycles to 4 is achieved at the expense of higher myelotoxicity.

A randomized phase III study to determine the efficacy of capecitabine in addition to a taxane and bevacizumab as first-line therapy in patients with metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1082-1082 ◽  
Author(s):  
Hans-Joachim Lueck ◽  
Kristina Luebbe ◽  
Joachim Bischoff ◽  
Nicolai Maass ◽  
Gabriele Feisel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Locally Advanced ◽  
Sample Size Calculation ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Open Label ◽  
Serious Adverse Events ◽  
Line Therapy

1082 Background: Conventional chemotherapy combined with novel molecular targeted agents has been proven effective and tolerable in metastatic breast cancer (MBC). Taxanes (T) plus bevacizumab (B) and T plus capecitabine (X) showed a benefit in progression free survival (PFS) compared to T alone. Life-threatening or highly symptomatic situations require poly-chemotherapies in MBC patients; therefore a combination of all 3 drugs appears reasonable. Methods: TABEA (NCT01200212) is a prospective, randomized, open label, phase III trial comparing T plus B +/- X as 1st-line therapy in MBC. Patients with histologically confirmed HER2- locally advanced or MBC were included. All patients received T (paclitaxel 80 mg/m2 i.v. d1,8,15 q22 or docetaxel 75 mg/m2 i.v. d1 q22) and B (15 mg/kg i.v. d1 q22) (TB) and were randomized to X (1800 mg/m² daily d1-14 q22) in addition and concurrently to TB (TBX) or TB alone. Randomization was stratified by receptor status, planned taxane, and disease free interval (≤ or >12 months). Primary objective was PFS. Secondary objectives were response rate and duration, clinical benefit rate (CR, PR, stable disease ≥ 24 weeks), 3yr overall survival, PFS in patients ≥ 65 years, toxicity, and compliance. Sample size calculation assumed a PFS of 10 and 13.3 months for TB and TBX, respectively (HR=0.75) requiring 432 patients and 386 events with 2-sided α=0.05 and β=0.2. Interim analysis was planned after 25% of required events (n=96). Results: Planned interim futility and safety analyses after 100 documented events in 202 patients have shown no efficacy benefit and higher toxicity in the TBX arm. For PFS, HR=1.061, 95% CI (0.715, 1.576) was observed, futility boundary was crossed. Overall grade 3-4 adverse events (e.g., thrombopenia, diarrhea, hand-foot-syndrome) (72.3 vs. 57.4%, p=0.039)and serious adverse events (40.6 vs. 24.8%, p=0.016) rates were higher for TBX after 16.3 months median follow up. There were 6 deaths in the TBX vs. 1 in the TB arm. Recruitment and therapy were stopped on 5th Oct 2012 following the advice from the IDMC. Conclusions: TABEA failed to show an improvement using the 3 drug regimen TBX in high-risk MBC patients. Clinical trial information: NCT 01200212.

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