POWER: An open-label, randomized phase III trial of cisplatin and 5-FU with or without panitumumab (P) for patients (pts) with nonresectable, advanced, or metastatic esophageal squamous cell cancer (ESCC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS4158-TPS4158 ◽  
Author(s):  
Markus Hermann Moehler ◽  
Ingo Ringshausen ◽  
Ralf Hofheinz ◽  
Salah-Eddin Al-Batran ◽  
Lothar Mueller ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Cell Cancer ◽  
Locally Advanced ◽  
Safety Data ◽  
Phase Iii ◽  
Tumor Control ◽  
Open Label ◽  
Phase Iii Trial ◽  
Metastatic Setting

TPS4158 Background: More than 50% of pts with esophageal cancer have locally advanced or metastatic disease at the time of initial diagnosis. For this group chemotherapy is increasingly used intending local and distant tumor control, improvement of quality of life (QoL) and longer survival. Previous data suggested that EGFR-targeting antibodies may be safely combined with cisplatin and 5-FU, and in addition may increase the efficacy of the standard cisplatin/5-FU regimen [Lorenzen et al, Ann Oncol2009; 20(10): 1667-1673]. Methods: In this open-label, randomized (1:1), multicenter, multinational phase III trial pts with nonresectable, advanced or metastatic ESCC, not eligible for definitive radiochemotherapy, are included. Pts have measurable or non-measurable disease according to RECIST 1.1 and an ECOG PS 0-1. Previous chemotherapy of ESCC in the metastatic setting, concurrent radiotherapy involving target lesions and previous exposure to EGFR-targeted therapy are excluded. Pts receive either CTX (cisplatin 100 mg/m² on day 1 and 5-FU 1000 mg/m²/d on day 1-4) or CTX + P (9 mg/kg on day 1). Cycles are repeated every 3 weeks until progression of disease. Tumor assessment is performed every 9 weeks. The primary objective is to demonstrate superiority of CTX + P over CTX alone in terms of overall survival. Secondary endpoints are progression-free survival, 1-year survival, response rate, safety and tolerability, and QoL. A translational analysis in tumor tissue and serum samples is included. 300 pts are planned to be enrolled for a power of 90% to reject the null hypothesis in which the median overall survival in the control and experimental groups are 6 and 9 months, respectively. 18 pts have been enrolled to date. A Data Monitoring Board will review safety data after 40, 100 and 200 pts. The clinical trial registry number is NCT1627379. Clinical trial information: NCT01627379.

Cisplatin/5-FU (CF) +/- panitumumab (P) for patients (pts) with non-resectable, advanced, or metastatic esophageal squamous cell cancer (ESCC): An open-label, randomized AIO/TTD/BDGO/EORTC phase III trial (POWER).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4011-4011 ◽  
Author(s):  
Markus H. Moehler ◽  
Peter C. Thuss-Patience ◽  
Baruch Brenner ◽  
Federico Longo ◽  
Johannes Meiler ◽  
...  
Keyword(s):  
Cell Cancer ◽  
Kidney Injury ◽  
Primary Objective ◽  
Phase Iii ◽  
Open Label ◽  
Skin Reactions ◽  
Phase Iii Trial ◽  
Metastatic Setting ◽  
Hand Foot Syndrome

4011 Background: Most ESCC pts have advanced disease at time of diagnosis. Chemotherapy (CTX) is used to improve quality of life (QoL) and overall survival (OS), but still with limited impact. Prior studies suggested increased efficacy of EGFR antibodies (AB) combined with CF (Lorenzen, Ann Oncol 2009). Methods: This open-label, randomized (1:1), multicenter, multinational phase III included pts with non-resectable, advanced or metastatic ESCC (RECIST1.1), not radiochemotherapy (RCTX) eligible and ECOG 0-1. Previous CTX in metastatic setting, concurrent RCTX and exposure to EGFR-AB were excluded. Pts received CF (C 100 mg/m² d1 + F 1000 mg/m²/d, d1-4) or CFP (9 mg/kg d1) q3 weeks until disease progression. Due to more Gr3-4 SAEs in the first 60 Pts with CFP, C was reduced to 80mg/m²d1 Tumor assessment was performed q9 weeks. Primary objective was OS: superiority of CFP (9 months [mo]) over CF (6 mo) with 300 pts (90% power). Results: Between 6.2012-5.2015, 146/155 pts were randomized. After interim analysis for futility, the trial was stopped. 60(83%) of CFP and 55(79%) of CF pts had any AE, mostly diarrhea, hypokalemia, hypomagnesaemia, rash, and hand-foot syndrome. Main Gr≥3 AEs were low neutrophils 21/ 24% and anemia 13/16 % for CFP vs CF, respectively. Gr 3-4 skin reactions and rash were higher in CFP (10%) vs CF (0%). Overall, 51/72 (71%) of CFP and 36/70 (51%) of CF had SAE. Main SAE were dysphagia, acute kidney injury, diarrhea, fevers and febrile neutropenia in 6/6%, 7/4%, 7/3%, 3/6% and 6/1% for CFP vs CF, respectively. For all CFP vs CF pts, median OS was 9.4 vs. 10.2 mo (hazard ratio (HR) 1.17, 95%CI 0.79-1.75; P=0.43). For 56 pts treated with cisplatin 100mg/m²d1, OS was 9.4 vs. 12.9 mo (HR 1.83, 95 % CI 0.98-3.42; P=0.06). After C was reduced (80mg/m²), OS (85 pts) favored CFP vs CF, with 9.8 vs. 8.3 mo (HR 0.84, 95%CI 0.49-1.43; P=0.51). Median PFS for all CFP vs CF pts, was 5.3 vs. 5.8 mo. (HR 1.21, 95%CI 0.85-1.73; P=0.29) respectively. Conclusions: Addition of Panitumumab to CF provided no additional benefit to chemotherapy alone as first-line treatment of ESCC. Biomarker program is going on for further analyses. Clinical trial information: NCT1627379.

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.

scholarly journals Adjuvant Capecitabine With Docetaxel and Cyclophosphamide Plus Epirubicin for Triple-Negative Breast Cancer (CBCSG010): An Open-Label, Randomized, Multicenter, Phase III Trial

2020 ◽  
Vol 38 (16) ◽  
pp. 1774-1784 ◽  
Author(s):  
Junjie Li ◽  
Keda Yu ◽  
Da Pang ◽  
Changqin Wang ◽  
Jun Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Safety Data ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Control Treatment ◽  
Open Label ◽  
Phase Iii Trial ◽  
Grade 3

PURPOSE Standard adjuvant chemotherapy for triple-negative breast cancer (TNBC) includes a taxane and an anthracycline. Concomitant capecitabine may be beneficial, but robust data to support this are lacking. The efficacy and safety of the addition of capecitabine into the TNBC adjuvant treatment regimen was evaluated. PATIENTS AND METHODS This randomized, open-label, phase III trial was conducted in China. Eligible female patients with early TNBC after definitive surgery were randomly assigned (1:1) to either capecitabine (3 cycles of capecitabine and docetaxel followed by 3 cycles of capecitabine, epirubicin, and cyclophosphamide) or control treatment (3 cycles of docetaxel followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide). Randomization was centralized without stratification. The primary end point was disease-free survival (DFS). RESULTS Between June 2012 and December 2013, 636 patients with TNBC were screened, and 585 were randomly assigned to treatment (control, 288; capecitabine, 297). Median follow-up was 67 months. The 5-year DFS rate was higher for capecitabine than for control treatment (86.3% v 80.4%; hazard ratio, 0.66; 95% CI, 0.44 to 0.99; P = .044). Five-year overall survival rates were numerically higher but not significantly improved (capecitabine, 93.3%; control, 90.7%). Overall, 39.1% of patients had capecitabine dose reductions, and 8.4% reported grade ≥ 3 hand-foot syndrome. The most common grade ≥ 3 hematologic toxicities were neutropenia (capecitabine, 136 [45.8%]; control, 118 [41.0%]) and febrile neutropenia (capecitabine, 50 [16.8%]; control, 46 [16.0%]). Safety data were similar to the known capecitabine safety profile and generally comparable between arms. CONCLUSION Capecitabine when added to 3 cycles of docetaxel followed by 3 cycles of a 3-drug anthracycline combination containing capecitabine instead of fluorouracil significantly improved DFS in TNBC without new safety concerns.

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]

Prognostic significance of HPV and p16 status in patients with oropharyngeal cancer treated on a large international phase III trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6004-6004 ◽  
Author(s):  
D. Rischin ◽  
R. Young ◽  
R. Fisher ◽  
S. Fox ◽  
Q. Le ◽  
...  
Keyword(s):  
Oropharyngeal Cancer ◽  
Cox Regression ◽  
Cell Cancer ◽  
Prognostic Significance ◽  
Phase Iii ◽  
Tumor Control ◽  
Eligibility Criteria ◽  
Cytoplasmic Staining ◽  
Phase Iii Trial ◽  
Hpv Status

6004 Background: Previous studies have reported that in patients with oropharyngeal cancer (OPC) the presence of human papilloma virus (HPV) is associated with an improved prognosis. We sought to determine the prognostic importance of HPV and p16 in patients with OPC treated with concurrent chemoradiation on a large international phase III trial. Methods: Patients with previously untreated Stage III or IV head and neck squamous cell cancer were randomized to receive definitive radiotherapy concurrently with either cisplatin or cisplatin plus tirapazamine. In this substudy, analyses were restricted to patients with OPC who received > 60 Gy and did not have major radiation deviations predicted to impact on tumor control. HPV 16/18 were detected by in situ hybridization and scored as detected or undetected. p16 was detected by immunohistochemistry. Nuclear and cytoplasmic staining intensity of tumor cells was scored as grade 0–3, with grade 2 and 3 called positive. Log rank and Cox regression used for survival analyses. p values were 2-sided . Results: 384 out of 861 patients had OPC and met the eligibility criteria. Slides were available for HPV assay in 195 and for p16 in 186, and for both in 173. 54/195 (28%) were HPV positive, 107/186 (58%) were p16 positive. HPV pos tumors were associated with better 2-year overall survival (OS) (94 v 77%, p = 0.007) and better failure-free survival (FFS) (86 v 75%, p = 0.035) compared to HPV neg tumors. Similarly p16 pos tumors were associated with better 2-year OS (92 v 75%, p = 0.004) and FFS (87 v 72%, p = 0.003) compared to p16 neg . After adjustment for stage, Hb and ECOG PS, HPV pos had better OS than HPV neg (HR 0.29, p = 0.018), and p16 pos had better OS than p16 neg (HR 0.39, p = 0.013). When the HPV and p16 results were combined the relative HRs for OS were: HPVpos/p16pos 0.35 (45 patients, 26% of cases), HPVpos/p16neg 0 (3pts, 2%), HPVneg/p16pos 0.73 (58pts, 33%), HPVneg/p16neg 1.79 (67 pts, 39%). Conclusions: Our results confirm the prognostic significance of tumor HPV status in oropharyngeal cancer treated with chemoradiation, but also show that p16 identifies a larger group with an improved prognosis. The HPV neg/p16 pos population has a better prognosis compared to patients with HPV neg/p16 neg tumors. No significant financial relationships to disclose.

PLATFORM: Planning treatment of oesophago-gastric (OG) cancer—A randomised maintenance therapy trial.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS187-TPS187 ◽  
Author(s):  
Catherine Cafferkey ◽  
Ian Chau ◽  
Fiona Thistlethwaite ◽  
Russell D. Petty ◽  
Naureen Starling ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Maintenance Therapy ◽  
Survival Benefit ◽  
Objective Response ◽  
Locally Advanced ◽  
First Line ◽  
Her2 Positive ◽  
Open Label ◽  
Line Chemotherapy

TPS187 Background: Outcomes for patients with advanced OG cancer remain poor, median overall survival for fit patients treated with platinum and fluoropyrimidine based chemotherapy is less than one year, with second line chemotherapy resulting in a modest (approximately 6 weeks) survival benefit for selected patients. Evidence from NSCLC trials suggests a survival benefit from maintenance treatment following first line chemotherapy. Emerging data also supports the use of immunotherapy in previously treated OG cancer. The PLATFORM study aims to evaluate maintenance therapy in patients with advanced OG cancer. Methods: This is a prospective, open label, multicentre, randomised phase II clinical trial which will recruit at multiple UK cancer centres. Eligible patients are those who have measurable stable disease or better following completion of first line chemotherapy (at least 6 cycles) for locally advanced unresectable or metastatic disease. First line chemotherapy regime should contain a platinum and 5-fluoropyridimine (with trastuzumab if HER2 +), doublet or triplet drug combinations are permitted. Maintenance strategies are split by HER 2 status. For HER2 negative patients these are: Arm A1: surveillance, Arm A2: capecitabine, Arm A3: MEDI 4736 (anti PDL1 inhibitor) and for HER2 positive patients; Arm B1: trastuzumab, Arm B2: in development. Target recruitment is six hundred and sixteen patients, 154 patients will be recruited to each arm, with an interim analysis following recruitment of 61 patients to each arm. An adaptive trial design enables ineffective treatments to be discontinued early, with the opportunity to add novel treatment arms as the trial progresses. Primary endpoint is progression free survival. Secondary endpoints are progression free rate at 3, 6 & 12 months, overall survival, objective response rate by RECIST 1.1, toxicity and analysis of efficacy endpoints according to biomarker status for selected arms. Thirty two patients have been registered for the study with 3 patients randomised, recruitment is ongoing. Clinical trial information: EUDRACT: 2014-002169-30.

Efficacy and safety results from AvaALL: An open-label, randomized phase III trial of standard of care (SOC) with or without continuous bevacizumab (Bev) treatment beyond progression (PD) in patients (pts) with advanced non-small cell lung cancer (NSCLC) progressing after first-line Bev and chemotherapy (chemo).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9004-9004 ◽  
Author(s):  
Jaafar Bennouna ◽  
Javier De Castro ◽  
Anne-Marie C. Dingemans ◽  
Frank Griesinger ◽  
Francesco Grossi ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Safety Data ◽  
Phase Iii ◽  
Positive Trend ◽  
Efficacy And Safety ◽  
First Line ◽  
Open Label ◽  
Phase Iii Trial ◽  
Significance Level ◽  
Safety Signals

9004 Background: The role of treatment with Bev beyond PD is unclear in the multiline treatment strategy of advanced NSCLC.AvaALL(NCT01351415), a multinational, open-label, randomized phase III trial, assessed continuous Bev and SOC beyond first PD (PD1) in pts with NSCLC following first-line treatment with platinum-based chemo plus Bev. Here we present efficacy and safety data from AvaALL. Methods: Pts with NSCLC who received 4–6 cycles of chemo + Bev and ≥2 cycles of maintenance Bev were randomized after PD1 to second-line SOC therapy (docetaxel, pemetrexed or erlotinib) ± Bev. After second PD (PD2) and third PD (PD3), pts received third-line or fourth-line SOC ± Bev treatment, respectively. Primary endpoint was overall survival (OS). Secondary endpoints were OS rates (6, 12, and 18-months [mos]), progression-free survival (PFS) from PD1 to PD2/from PD2 to PD3, overall response rate (ORR), disease control rate (DCR), and safety. Data cut-off: 24 Jun 2016. Results: Overall, 485 pts were randomized (n = 475 treated). Pt characteristics were well balanced between the two arms. Bev plus chemo resulted in a median OS of 11.9 mos versus 10.2 mos for SOC alone (HR 0.84, 90% CI 0.71–1.00; p = 0.1016; 387 OS events). The primary endpoint was not met (416 OS events were required, at 10% two-sided significance level). OS rates were 10% higher in the Bev arm vs SOC alone at 6-, 12- and 18-mos. Median PFS2 was 4.9 mos with Bev vs 3.8 mos with SOC (HR 0.85, 90% CI 0.72–1.00; p = 0.0907). PFS3 was significantly improved (3.5 mos for Bev, 2.4 mos for SOC; HR 0.65, 90% CI 0.51–0.84; p = 0.0047). ORR and DCR were slightly higher in the Bev arm versus the SOC arm (ORR 9.7% vs 6.7%; DCR 86.2% vs 79.3%, respectively). No new safety signals were identified. Grade ≥3 adverse events were reported in 78.2% of Bev pts and 61.6% of SOC pts. Conclusions: Although the primary endpoint was not met, efficacy data suggest a positive trend for continued Bev plus SOC after PD1 compared with SOC alone. No cumulative safety signals were identified. Clinical trial information: NCT01351415.

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