Pemetrexed monotherapy as salvage treatment in metastatic colorectal cancer patients who failed standard chemotherapy: A phase II single-arm prospective trial.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 840-840
Author(s):  
Sung Won Lim ◽  
Jangho Cho ◽  
Jeeyun Lee ◽  
Se Hoon Park ◽  
Joon Oh Park ◽  
...  
Keyword(s):  
Folic Acid ◽  
Phase Ii ◽  
Performance Status ◽  
Prospective Trial ◽  
Response Duration ◽  
Complete Response ◽  
Vitamin Supplementation ◽  
Vitamin Supplement ◽  
Open Label ◽  
Ecog Performance Status

840 Background: We designed a single-arm, open label phase II study to determine the efficacy and toxicity of pemetrexed monotherapy with vitamin supplement in refractory colorectal (CRC) patients who failed standard treatments, including 5-FU, oxaliplatin, and irinotecan with or without biologic agents. Methods: Patients were treated with pemetrexed 500 mg/m2 on day 1, every 3 weeks, with folic acid and vitamin B12 supplementation. Patients began vitamin supplementation with B12 intramuscular injection (1000 mcg) every 9 weeks starting 1 week before the first pemetrexed dose, and patients received daily oral folic acid (1 mg) starting at least 5 days before the first pemetrexed dose. Treatment was continued until disease progression or intolerable toxicity was observed. Results: Between June 2016 and October 2016, 24 patients were enrolled in this study. One patient withdrew content, leaving a total of 23 patients to be evaluated. The median age of the patients was 54.0 years (range, 23.0 to 67.0), and the median ECOG performance status was 1 (1-2). The median number of previous systemic chemotherapies was 3 (range, 2 to 5). No complete response and no partial response were observed among the patients. Stable disease was observed in 10 patients (43.4%), and 7 patients had a response duration of 2 months or more. The median PFS was 1.6 months (95% CI, 1.1 to 2.0) and the median OS was 9.8 months (95% CI, 5.9 to 13.6). Only one patient experienced treatment-related toxicity of grade 3 or more. Neither hematologic toxicities nor dose reduction due to treatment-related toxicities were observed. There was no treatment-related death. Conclusions: Pemetrexed monotherapy showed moderate disease control and an acceptable toxicity profile as salvage therapy for refractory CRC. Clinical trial information: NCT02588781.

Phase II study with preoperative oxaliplatin (O), cisplatin (P), 5-fluorouracil (F) (OPF) and radiation (XRT) in patients with esophageal (ES), gastroesophageal (GE), and gastric (G) cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15612-e15612
Author(s):  
M. Pera ◽  
R. Gallego ◽  
M. Martin-Richard ◽  
C. Montagut ◽  
M. Iglesias ◽  
...  
Keyword(s):  
Phase Ii ◽  
Median Overall Survival ◽  
Phase Ii Study ◽  
Performance Status ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Surgical Oncology ◽  
Primary Objective ◽  
Ecog Performance Status ◽  
Eligibility Criteria

e15612 Background: A phase I study showed the feasibility of the triplet combination (OPF) with XRT in ES and GE cancer (Maurel et al, IJRBOP, 2005). We conducted a phase II study to evaluate the efficacy of the regimen. Methods: Enrolled pts had resectable, high-risk (HR) based on endoscopic ultrasonography (EUS) (uT3, uN1 or uT4 if deemed resectable) ES, GE and G cancer. The primary objective was to determine the pathologic complete response (pCR). If 2 or more pCR were reported in the first 18 pts treated, enrollment continues with 23 additional pts. Eligibility criteria: squamous cell or adenocarcinoma of the ES, GE or G cancer and ECOG Performance status (PS) 0–1. Staging was done with EUS and computed spiral tomography. Laparoscopic staging was mandatory for pts with ES, GE and G adenocarcinoma. Pts received 2 cycles of O 85 mg/m2, P 55 mg/m2, F (3 g/m2 in 96h CI) q4w, with concomitant 45 Gy XRT in 25 fractions; surgery was planned 5–8 weeks after XRT. All pathological specimens were reviewed by a unique pathologist and regression analysis was recorded using Cologne (C) and M.D.Anderson (MDA) classification for ES and European Journal of Surgical Oncology (EJSO) for GE and G. Results: Between 5/04 to 12/07, 41 pts were enrolled in 5 Spanish Institutions. Median age 62 yrs (39–75 yrs); Male/female 83%/17%; PS 0/1 27%/73%; ES/GE/G 39%/32%/29%; EUS stageT3N0 (20%), T2–3N1 (65%) and T4 (10%). G3/4 adverse events included asthenia (27%), infection (7%), diarrhea (7%) and stomatitis (5%). There were 2 toxic deaths. Of the 31 pts who underwent surgery, there were R0=94%/R1=3%/R2= 3%. 7/41 pts (17%) achieved pCR. Using C and MDA classification, 9/14 (61%) and 12/14 (85%) ES achieved grade IV/III and P0/P1 regression, respectively. With EJSO classification 3/17 (18%) GE and G tumors achieved pCR. Median time to progression or death (PFS) was 16.2 (CI:12.2-NR) months (mo). Median overall survival (OS) was 28.9 mo. (CI: 22.5-NR). Conclusions: Although in the whole group pCR, PFS and OS does not appear superior to results achieved in other trials with preoperative P/F/XRT in HR pts, the OPF regimen seems specially active in ES cancer. No significant financial relationships to disclose.

MAVERICC: A randomized phase II study of mFOLFOX6-bevacizumab (BV) versus FOLFIRI-BV with prospective biomarker stratification in previously untreated metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS3635-TPS3635 ◽  
Author(s):  
Sachdev P. Thomas ◽  
Suprith Badarinath ◽  
Richard H. Greenberg ◽  
Sang Y. Huh ◽  
Kulumani M Sivarajan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Hepatic Metastases ◽  
Predictive Biomarkers ◽  
Snp Markers ◽  
Open Label ◽  
Ecog Performance Status ◽  
The Impact

TPS3635^ Background: The identification of prognostic and predictive biomarkers could significantly improve the risk-benefit ratio and cost-effectiveness of 1st-line mCRC regimens. This is the first prospective study of tumoral ERCC1 (chemo-resistance marker to platinum compounds) and plasma VEGF-A as potential biomarkers for oxaliplatin- and BV-containing regimens, respectively, in an effort to further define the optimal chemotherapy backbone with biologic therapies, including BV, for mCRC. Methods: In this randomized, open-label, global, phase II study, patients (N=360) with histologically or cytologically confirmed CRC and ≥1 measurable metastatic lesion are stratified at screening by tumoral ERCC1 mRNA expression (high vs low, cutoff of 1.7 [ERCC1/β-actin mRNA]). Eligibility criteria include completion of adjuvant therapy >12 months before screening and an ECOG performance status ≤1. Blood samples are collected to quantify plasma VEGF-A levels. Patients within each ERCC1 stratification group are randomized 1:1 to mFOLFOX6-BV or FOLFIRI-BV administered in 2-week cycles. BV will be given at a dose of 5 mg/kg IV q2w. Patients will remain on study treatment until disease progression (PD) or unacceptable toxicity. If oxaliplatin or irinotecan need to be discontinued, BV and 5-fluorouracil or capecitabine are to be continued until PD. The primary objectives are: 1) to assess ERCC1 and VEGF-A as biomarkers of progression-free survival (PFS) for oxaliplatin- and BV-containing regimens in 1st-line mCRC, and 2) within ERCC1 high patients, to test whether FOLFIRI-BV is associated with a prolonged 1st-line PFS compared to mFOLFOX6-BV. Secondary objectives include assessing the impact of these markers on overall survival, objective response, hepatic metastases resection, and safety. Exploratory endpoints include correlative analyses with additional tumor tissue, blood, and SNP markers. The first patient was enrolled in August 2011. An interim biomarker distribution assessment of the first 100 patients is planned, and the evaluation of the primary endpoints is estimated for early 2015. Clinicaltrials.gov: NCT01374425.

Bevacizumab (Bmab) in combination with uracil-tegafur (UFT) and oral leucovorin (LV) in elderly patients (≥ 75 years old) with metastatic colorectal cancer (mCRC): A multicenter phase II trial (J-BLUE study).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 588-588
Author(s):  
Mitsuo Shimada ◽  
Tomohiro Nishina ◽  
Jun Higashijima ◽  
Toshikazu Moriwaki ◽  
Toshiki Masuishi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Elderly Patients ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Effective Treatment Option ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Ecog Ps

588 Background: Now fluoropyrimidine plus Bmab is considered a recommendable option to the majority of elderly mCRC patients who are deemed inappropriate for the standard doublet chemotherapy with biologics. Our previous phase II study of UFT/ LV in elderly mCRC patients (≥75 years old) had demonstrated acceptable safety and efficacy (overall response rate [ORR] 33%, progression-free survival [PFS] 5.3 months, overall survival [OS] 18 months). The aim of the present study was to investigate the efficacy and safety of Bmab in combination with UFT/LV for elderly mCRC patients. Methods: This study was designed as a single-arm, open-label, multicenter, cooperative group (SGOSG-TCTG) clinical trial (trial registration: UMIN000003515). Key eligibility criteria included age ≥75 years, ECOG performance status (PS) 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ functions. Patients received UFT 300mg/m2/day and LV 75mg/body/day on days 1-21 followed by 7 days rest, and intravenous administration of Bmab 5mg/kg on days 1 and 15. Treatment repeated every 28 days. The primary endpoint was PFS, and secondary endpoints were ORR, OS, and safety. Results: A total of 55 patients were enrolled from 15 institutions between Aug 2008 and Mar 2012. Among them, 52 eligible patients were evaluated. Median age was 80 years (range: 75-87). ECOG PS 0 was 73%. Median PFS was 8.2 months (95% confidence interval [CI], 6.2-10.3, events in 86.5%). Confirmed ORR was 40.4% (95% CI, 27.0-54.9%). Median OS was 18.7 months (95% CI, 10.3-27.0, events in 48%). The most common grade ≥3 treatment-related adverse events were hypertension (11.5%), fatigue (7.7%), nausea (5.8%), and diarrhea (5.8%). The treatment-related death occurred in 2 (3.8%) patients. Main reasons for discontinuation of treatment were disease-progression (62.5%) and toxicity (27.1%). Conclusions: Bmab in combination with UFT/LV is tolerable and effective treatment option for elderly patients (≥75 years old) with mCRC. Further trial with Bmab plus UFT/LV targeting elderly mCRC patients would be warranted. Clinical trial information: 000003515.

Phase II study of trifluridine/tipiracil (FTD/TPI) and oxaliplatin as induction chemotherapy (IC) in resectable esophageal and gastroesophageal junction adenocarcinoma (EGAC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS464-TPS464
Author(s):  
Sarbajit Mukherjee ◽  
Hussein Assi ◽  
Christos Fountzilas ◽  
Kristopher Attwood ◽  
Patrick McKay Boland ◽  
...  
Keyword(s):  
Phase Ii ◽  
Metabolic Response ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Fixed Dose ◽  
Open Label ◽  
Ecog Performance Status ◽  
Total N

TPS464 Background: Neoadjuvant chemoradiation (CRT) followed by surgery is a standard approach for localized EGAC. Despite multimodality treatment, 5-year overall survival (OS) is less than 50%, with pathologic complete response (pCR) rates of 20%. Achievement of pCR is associated with an improved OS. We propose to use a novel combination of FTD/TPI and oxaliplatin as IC. We hypothesize that IC before CRT will increase the pCR rate in localized EGAC. Methods: This is an open-label, multicenter phase II trial. Patients (pts) with potentially resectable loco-regional EGAC are eligible. Pts. should have adequate organ function, ECOG performance status of 0 –1, age < 76 years, and endoscopic ultrasound-determined node-positive disease with any T-stage, or T3-T4a with any N stage. Pts. with T4b or M1 disease will be excluded. Pts. will receive three cycles of IC with FTD/TPI and oxaliplatin. Based on the maximum tolerated dose (MTD) observed in a phase I trial, FTD/TPI will be administered 35 mg/m² BID, days 1–5 every 14 days, with a fixed dose of oxaliplatin 85 mg/m² (day 1). Pts will then undergo concurrent CRT (standard radiation dose of 5040 cGY will be utilized) with weekly Carboplatin (AUC 2) and Paclitaxel (50 mg/m2) for 6 weeks followed by surgery. Our primary objective is to evaluate the pCR rate. The secondary objectives include evaluation of 2-year disease-free survival (DFS), 2-year OS, and assessment of toxicities of the IC. As a correlative endpoint, circulating tumor DNA level will be correlated with disease recurrence and metabolic response on PET CT. Assuming a historic pCR rate of 20% with standard CRT, 41 pts (enrollment of up to 45 pts accounting for non-evaluable pts) are needed to show a 15% increase in pCR with IC with 80% power at one-sided significance level of α = 0.1. In stage 1, n1= 22 evaluable pts will be enrolled. If there is 5 or more pCRs, an additional n2= 19 pts will be enrolled in stage 2. If 12 or more pCRs are observed in the total n = 41 evaluable pts, then the proposed treatment regimen will be considered promising for further study. We anticipate accrual over a 2-year period from 3 sites. Clinical trial information: NCT04097028.

scholarly journals Safety and Pharmacokinetics of Motesanib in Combination with Panitumumab and Gemcitabine-Cisplatin in Patients with Advanced Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Howard Burris ◽  
Joe Stephenson ◽  
Gregory A. Otterson ◽  
Mark Stein ◽  
Jesse McGreivy ◽  
...  
Keyword(s):  
Growth Factor ◽  
Performance Status ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Thromboembolic Events ◽  
Open Label ◽  
Ecog Performance Status ◽  
Venous Thromboembolic Events

Purpose. The aim of this study was to assess the safety and tolerability of motesanib (an orally administered small-molecule antagonist of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptor, and Kit) when administered in combination with panitumumab, gemcitabine, and cisplatin.Methods. This was an open-label, multicenter phase 1b study in patients with advanced solid tumors with an ECOG performance status ≤1 and for whom a gemcitabine/cisplatin regimen was indicated. Patients received motesanib (0 mg [control], 50 mg once daily [QD], 75 mg QD, 100 mg QD, 125 mg QD, or 75 mg twice daily [BID]) with panitumumab (9 mg/kg), gemcitabine (1250 mg/m2) and cisplatin (75 mg/m2) in 21-day cycles. The primary endpoint was the incidence of dose-limiting toxicities (DLTs).Results. Forty-one patients were enrolled and received treatment (including 8 control patients). One of eight patients in the 50 mg QD cohort and 5/11 patients in the 125 mg QD cohort experienced DLTs. The maximum tolerated dose was established as 100 mg QD. Among patients who received motesanib (n=33), 29 had motesanib-related adverse events. Fourteen patients had serious motesanib-related events. Ten patients had motesanib-related venous thromboembolic events and three had motesanib-related arterial thromboembolic events, two of which were considered serious. One patient had a complete response and nine had partial responses as their best objective response.Conclusions. The combination of motesanib, panitumumab, and gemcitabine/cisplatin could not be administered consistently and, at the described doses and schedule, may be intolerable. However, encouraging antitumor activity was noted in some cases.

Phase II trial of panobinostat (LBH589) in patients (pts) with refractory metastatic colorectal cancer (MCRC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 582-582 ◽  
Author(s):  
Philip Jordan Gold ◽  
David A. Smith ◽  
Desiree Iriarte ◽  
Barry Boatman ◽  
Henry G. Kaplan
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Median Number ◽  
Open Label ◽  
Ecog Performance Status ◽  
Treatment Regimes ◽  
Open Label Phase ◽  
Secondary Endpoints

582 Background: LBH589 is a novel histone deacetylase inhibitor (HDACi) which induces apoptosis of tumor cells. LBH589 has been shown to cause regression of colon cancer in animal models and phase I trials have shown the agent to be well tolerated, providing rationale for studying this agent in pts with MCRC. Methods: This was a multicenter, open-label phase II study of single agent LBH589 in patients with MCRC who failed at least 2 prior regimens for metastatic disease. Measurable disease, adequate organ function and ECOG performance status of 0-2 were required. Pts received LBH589 30mg po on M/W/F until disease progression. Pts were evaluated for toxicity every 2 weeks and for response every 8 weeks. The primary endpoint was overall survival. Secondary endpoints included response rate, time to progression (TTP), and toxicity. Results: 29 pts were enrolled (16 male, 13 female). The median age was 59 (range 41-76). The median number of prior treatment regimes was 3 (2-11). The median survival was 5.1 months (range 1-24+). There were no objective responses. 3 pts had SD at 8 weeks. The median TTP was 7.7 weeks (range 1-38.). Six pts had grade 4 thrombocytopenia requiring platelet transfusion. Nine pts required dose reductions for toxicity. Conclusions: Single-agent LBH589 was not associated with objective tumor responses in this heavily pre-treated pt population. However, the median survival was comparable to that seen in other trials of single agent targeted therapy in the treatment of refractory MCRC. Thrombocytopenia was significant, and may complicate potential trials of combination therapy.

XELOX with bevacizumab in elderly patients age 75 or older with metastatic colorectal cancer: Results of a planned interim analysis for multicenter phase II ASCA study.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 502-502 ◽  
Author(s):  
Keiichiro Ishibashi ◽  
Yoshinori Munemoto ◽  
Masaki Matsuoka ◽  
Taishi Hata ◽  
Michiya Kobayashi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Renal Function ◽  
Elderly Patients ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Performance Status ◽  
Primary Objective ◽  
Open Label ◽  
Ecog Performance Status ◽  
Grade 3

502 Background: Combination chemotherapy of capecitabine plus oxaliplatin (XELOX) with bevacizumab is commonly used as standard chemotherapy for metastatic colorectal cancer (mCRC). A previous meta-analysis showed that there was no difference between two age groups of <65 years and ≥65 years on overall survival (OS) after treatment with chemotherapy with bevacizumab. However, the safety and efficacy of XELOX with bevacizumab in elderly patients (pts) ≥75 years with mCRC remain unclear. Methods: This study was an open-label multicentre phase II study to evaluate the efficacy and safety of XELOX with bevacizumab in pts ≥75 years with metastatic CRC. The primary objective was to assess progression-free survival (PFS). The secondary endpoints were the safety, response rate (RR), time to treatment-failure (TTF) and OS. Results: 36 pts were enrolled. Pts characteristics were; median age 78 (range 75-86); male/female, 21/15; ECOG performance status 0/1, 30/6; colon/rectum 24/12, creatinine clearance (CCr) 60.2 ml/min (range 32.6-84.6). Median follow-up period was 220 days. RR was 55.6% and median TTF was 209 days. The median PFS and median OS are not reached. Grade 3 or 4 adverse events (AEs) were reported in 22 pts (62.8%). Common grade 3 or 4 AEs were hypertension (11.4%), leukopenia (20.0%), peripheral sensory neuropathy (14.3%), hand foot syndrome (8.6%), and fatigue (8.6%). Examining the relationship between renal function (CCr) and AEs, the incidence of Grade 3 or 4 AEs in the lower CCr group was significantly higher than that in the higher CCr group (61.6% vs. 47.8%; p=0.013); hematological toxicities (87.5% vs. 14.8%; p=0.0003) and non-hematological toxicities (61.5% vs. 11.1%; p=0.018). Conclusions: XELOX with bevacizumab is safely administered in elderly patients ≥75 years. Renal function (CCr) could be a good predictive marker for grade 3 or 4 AEs. Clinical trial information: UMIN000003500.

Phase II study of nivolumab and ipilimumab for advanced bladder cancer of variant histologies (BCVH).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4518-4518 ◽  
Author(s):  
Bradley Alexander McGregor ◽  
Matthew T Campbell ◽  
Wanling Xie ◽  
Arlene O. Siefker-Radtke ◽  
Amishi Yogesh Shah ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Complete Response ◽  
Median Number ◽  
Small Cell ◽  
Blood Collection ◽  
Ecog Performance Status ◽  
Prior Therapy ◽  
Platinum Based Chemotherapy ◽  
Poor Outcomes

4518 Background: Patients with BCVH have poor outcomes and data regarding the management of this heterogeneous group of patients is limited. Nivolumab and ipilimumab has demonstrated safety and efficacy in urothelial carcinoma and other malignancies. In this multicenter, single arm, multi-cohort phase II trial we evaluate the efficacy of nivolumab and ipilimumab in patients with BCVH and other advanced rare genitourinary cancers (NCT 03333616). Herein, we report the preliminary results of the fully accrued BCVH cohort. Methods: Eligible patients had metastatic BCVH, ECOG performance status of 0-2 and were either untreated or had received any number of lines of prior therapy excluding prior immunotherapy. Patients underwent a baseline biopsy and blood collection for correlative studies and received treatment with nivolumab 3 mg/kg and ipilimumab 1 mg/kg intravenously every 3 weeks for 4 cycles with continued maintenance of nivolumab 480 mg IV every 4 weeks. The primary endpoint was overall response rate (ORR) by RECIST 1.1. Results: 19 BCVH patients were enrolled at 4 institutions between 4/2018 and 1/2019: squamous cell (n = 6), small cell (n = 3), adenocarcinoma (n = 3), urachal (n = 5), plasmacytoid (n = 1), and spindle cell (n = 1). 13 (68%) patients had received prior systemic therapy including platinum-based chemotherapy in 92% patients. Median number of cycles of ipilimumab plus nivolumab received was 3 (range 1-8) and median follow-up was 3.6 (0.3-8.8) months. 13 patients had undergone at least one scan; ORR was 31% (4/13, 80%CI: 14-52%), with partial responses seen in small cell carcinoma (n = 2), urachal (n = 1) and a complete response in 1 patient with plasmacytoid carcinoma. 3 patients (16%) developed treatment-related grade 3 toxicities with 1 (5%) grade 4 toxicity. Conclusions: Nivolumab and ipilmumab resulted in objective responses in a subset of patients with BCVH with manageable toxicities. Updated clinical and correlative data will be presented. This combination may warrant further investigation in patients with BCVH, which has substantial unmet needs. Clinical trial information: NCT 03333616.

Results of a randomized phase II trial of amrubicin (AMR) versus topotecan (Topo) in patients with extensive-disease small cell lung cancer (ED-SCLC) sensitive to first-line platinum-based chemotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8028-8028
Author(s):  
R. Jotte ◽  
P. Conkling ◽  
C. Reynolds ◽  
L. Klein ◽  
J. F. Fitzgibbons ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Open Label ◽  
Ecog Performance Status ◽  
Prior Therapy ◽  
Platinum Based Chemotherapy ◽  
Ecog Ps

8028 Background: SCLC presents as ED-SCLC in 60%-70% of patients (pts). AMR, a synthetic anthracycline, is approved for these pts in Japan. We compare the efficacy and safety of single-agent AMR vs topotecan in non-Japanese pts with 2nd-line ED-SCLC sensitive to 1st-line platinum-based chemotherapy. Methods: This phase II, open-label, multicenter study enrolled pts with ED-SCLC sensitive to 1st-line platinum-based chemotherapy (recurrence or progression ≥90 days from 1st-line treatment). Pts aged ≥18 years with ECOG performance status (PS) ≤2 and only 1 prior therapy were eligible. Pts were randomized (2:1) to receive IV AMR 40 mg/m2/d (d, 1–3) or IV topotecan 1.5 mg/m2/d (d 1–5) and treated every 21 days until progression, unacceptable toxicity, or withdrawal. The primary endpoint, overall response rate (ORR, complete + partial response), used RECIST criteria. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: In all, 76 pts were randomized to AMR (n=50) or topotecan (n=26) with AMR given for a median of 6 cycles (range 1–16) and topotecan 3 cycles (1–16). AMR significantly improved ORR rates vs topotecan (p<0.012; Table ). Median PFS/OS was 4.3 months (95% CI 2.0, 6.1)/9.3 months (95% CI 5.7, 12.0) with AMR vs 3.5 months (95% CI 2.1, 6.3)/8.9 months (95% CI 4.8, 13.8) with topotecan. There was a higher proportion of ECOG PS 2 pts in the AMR group (n=6) vs the topotecan group (n=2). A trend towards improved OS was observed in the ECOG 0–1 subgroup of 68 pts: median OS was 10.5 months with AMR vs 9.7 months with topotecan. The most common grade ≥3 adverse events with AMR vs topotecan were neutropenia (53% vs 74%), thrombocytopenia (31% vs 52%) and leukopenia (27% vs 30%). Three AMR pts (6%) and 1 topotecan pt (4%) died of neutropenic infection. Conclusions: AMR significantly improves ORR and has acceptable tolerability as 2nd-line treatment in pts with sensitive ED-SCLC. [Table: see text] [Table: see text]

Maintenance sunitinib postchemotherapy (CT) in patients (pts) with advanced urothelial carcinoma (UC): A randomized placebo controlled phase II trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5073-5073 ◽  
Author(s):  
D. Bradley ◽  
S. Daignault ◽  
D. C. Smith ◽  
D. Nanus ◽  
S. Tagawa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tyrosine Kinases ◽  
Performance Status ◽  
Complete Response ◽  
Clinical Activity ◽  
Progression Rate ◽  
Open Label ◽  
Ct Dose ◽  
Best Response ◽  
Inhibition Of Angiogenesis

5073 Background: Although response to CT is common in pts with advanced UC it is rarely durable. Sunitinib is an oral small molecule inhibitor of receptor tyrosine kinases regulating angiogenesis including VEGFR-1, -2, -3, and PDGFR-α, -β with demonstrated antitumor activity in a variety of solid tumors. Inhibition of angiogenesis following CT may delay disease progression. Therefore, we are evaluating maintenance sunitinib in a phase II study. Methods: Pts with advanced UC, > stable disease (SD) after 4–6 cycles of CT, a performance status (PS) 0–2, adequate organ function and < 42 days from last CT dose were randomized to sunitinib 50 mg or placebo; 4 weeks (wks) on 2 off in 6 wk cycles. Pts were stratified by response to CT. Disease was assessed every 12 wks. Pts were unblinded for progression or unacceptable adverse events (AEs), with placebo pts offered open label sunitinib. The primary end point is 6 month progression rate using a modified version of the randomized selection design (Simon 1985). 42 pts/arm are to be accrued to allow selection of the superior arm with 90% probability. Other endpoints include safety, response rate (RR), time to progression, median survival, RR to open label sunitinib and correlation of changes in serum VEGF and sVEGFR-2 levels with outcome. Results: To date, 28 pts have been registered and 26 have completed > 12 wks of therapy. Median age is 69 years (48–81) and PS is 1 (37% PS 0, 52% PS 1). 12% had a complete response (CR) to prior CT, 46% a partial response (PR) and 42% SD. 14 pts have progressed after a median of 2 cycles (range 1–12). 7 pts received open label sunitinib at progression, 1/7 remains on treatment. Median duration on open label therapy is 2.2 months (11 days-15 months). Best response to open label therapy to date is progressive disease (2 pts), SD (2 pts) for 24 wks, PR in 1 pt through 60 weeks and 2 pts have not reached first assessment. Grade 3 AEs on open label sunitinib included: bladder hemorrhage, increased creatinine, fatigue, thrombocytopenia and hand-and-foot syndrome. No grade 4 or 5 AEs were observed. Conclusions: Preliminary results indicate that maintenance sunitinib post CT is feasible in advanced UC pts and is associated with clinical activity. Supported by Pfizer. [Table: see text]

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