Avelumab as single agent for patients with metastatic or locally advanced urothelial cancer PD-L1+ unfit for cisplatin: The ARIES study.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS596-TPS596
Author(s):  
Roberto Iacovelli ◽  
Sebastiano Buti ◽  
Consuelo Buttigliero ◽  
Rocco De Vivo ◽  
Claudia Caserta ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Standard Dose ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Ecog Performance Status ◽  
Progression Of Disease ◽  
Unfit Patients ◽  
Unselected Population

TPS596 Background: Urothelial cancer (UC) is the ninth most common cancer worldwide, this tumour has a poor prognosis when in advanced stage. Cisplatin-based chemotherapy is considered the most effective treatment but more than 50% of patients are considered not eligible ( cis-unfit) for this regimen and have a median survival of only 6-9 months. In the past years, the most used chemotherapy regimen for cis-unfit patients was the combination of carboplatin and gemcitabine. Two single arm studies tested the anti-PD-L1/PD1 monoclonal antibodies atezolizumab and pembrolizumab and reported a response rate of 25% with good safety profile in an unselected population for PD-L1 expression. Recently, atezolizumab alone showed longer OS compared to carboplatin-gemcitabine regimen. Avelumab is another fully human anti-PD-L1 IgG1 antibody already tested in urothelial and in other cancers with a promising safety and efficacy profile. Methods: The single arm, phase II ARIES trial (NCT03891238), aims to evaluate the activity and efficacy of avelumab in patients with metastatic or locally advanced UC considered cis-unfit with PD-L1 expression ≥5%. Overall survival is the primary endpoint. Cis-unfit definition includes at least one of the following characteristics (i) ECOG-Performance status=2; (ii) creatinine clearance <60 ml/min; (iii) grade ≥2 peripheral neuropathy or hearing loss; (iv) disease progression within six months after a previous adjuvant/neoadjuvant treatment with cisplatin-based therapy. Avelumab will be administered at standard dose of 10 mg/kg in 1-hour intravenous infusion every 2 weeks (Q2W). Sixty-seven patients will be enrolled, and supportive care is allowed during the study. Avelumab may be continued after radiological progression of disease at physician’s discretion if an improvement of symptoms or not new symptoms will be reported. The study is currently ongoing in twenty centres in Italy. Clinical trial information: NCT03891238.

Baby-step chemotherapy as a way to deliver chemotherapy in poor PS small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17500-e17500
Author(s):  
Vanita Noronha ◽  
Vijay Patil ◽  
Amit Joshi ◽  
Vamshi Muddu ◽  
Kumar Prabhash
Keyword(s):  
Low Dose ◽  
Positive Impact ◽  
Standard Dose ◽  
Performance Status ◽  
Single Agent ◽  
Median Number ◽  
Ecog Performance Status ◽  
Full Dose ◽  
Grade 3 ◽  
Low Dose Chemotherapy

e17500 Background: Majority of patients with SCLC present with advanced stage and poor ECOG performance status. Hence delivery of adequate dose of chemotherapy is compromised. We hypothesized that initial low-dose chemotherapy might improve PS and enable administration of standard-dose chemotherapy, thus extending benefit of chemotherapy to otherwise ineligible patients. Methods: 30 patients with ECOG performance status 2-4 received low-dose chemotherapy consisting of either single agent carboplatin at AUC 2 or an abbreviated course of platinum-etoposide. Patients whose PS improved got full-dose chemotherapy with the standard regimen of platinum-etoposide. Demographic details, toxicity, time to progression and overall survival were analyzed. Univariate and multivariate analysis was performed to determine factors associated with TTP and OS. Results: Median age was 58 years with male predominance. The PS was IV in 9, III in 20 and II in 1 patient. Extensive-stage and limited-stage disease was seen in 24 and 6 patients respectively.15 patients received single-agent carboplatin, 10 patients abbreviated cisplatin-etoposide, 1 patient each cyclophosphamide and cisplatin-etoposide and 3 patients refused chemotherapy. Major grade 3-4 toxicity was mucositis in 1, loose motions in 1 and hyponatremia in 4 patients. There was no grade 3- 4 haematological toxicity. The median number of dose-reduced cycles was 1 and 3 patients received more than 2 cycles. 22 patients were eligible and willing for full-dose chemotherapy. The median time to start of full-dose chemotherapy was 11.5 days (4-26 days). The median number of cycles of standard-dose chemotherapy was 5 (1-6) with 16 completing planned schedule. Grade 3-4 toxicity was neutropenia in 50%, febrile neutropenia in 25%, loose motions in 25% and hyponatremia in 40%. The overall TTP and OS was 182 days and 263 days respectively. Presence of SIADH (p = 0.02) and completion of standard treatment (p = 0.001) had a positive impact on TTP while completion of treatment (p = 0.01) and normal LDH (p = 0.03) had a positive impact on OS. Conclusions: Low-dose chemotherapy is well-tolerated and might help in extending the benefit of standard-dose chemotherapy to otherwise ineligible patients.

ABC-08: A phase Ib, multi-centre, open-label study of a first-in-class nucleotide analogue NUC-1031 in combination with cisplatin in patients with locally advanced/metastatic biliary tract cancers.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS544-TPS544 ◽  
Author(s):  
Mairead Geraldine McNamara ◽  
John A. Bridgewater ◽  
Daniel H. Palmer ◽  
Harpreet Singh Wasan ◽  
David Ryder ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Standard Dose ◽  
Performance Status ◽  
Locally Advanced ◽  
Clinical Activity ◽  
Cancer Resistance ◽  
Open Label ◽  
Ecog Performance Status ◽  
Biliary Tract Cancers ◽  
Phase Ib

TPS544 Background: The UK ABC-02 study established cisplatin and gemcitabine as the reference regimen for first-line treatment of patients (pts) with advanced biliary tract cancers (BTCs) (median overall survival (OS): 11.7 months). No clinical studies since ABC-02 have reported an extension in OS, and therefore effective new agents/combinations are required. NUC-1031 was designed to improve on gemcitabine’s relatively poor efficacy by overcoming its associated key cancer resistance mechanisms, through cellular uptake independent of nucleoside transporters, activation independent of deoxycytidine kinase and protection from cytidine deaminase inactivation, resulting in over 200x the intracellular levels of the anti-cancer metabolite, dFdCTP, greater stability and reduction in the generation of toxic metabolites. NUC-1031 showed activity as monotherapy in a phase I/II study in 7 pts with BTC, refractory to all standard treatments (Blagden et al ASCO 2015; abstract 2514). Methods: ABC-08 is a multi-centre phase Ib study of NUC-1031 combined with cisplatin in pts with non-resectable or recurrent/metastatic cholangiocarcinoma, gallbladder or ampullary carcinoma, aged ≥18 years with an ECOG performance status of 0-1, who have received no prior systemic therapy. The starting dose for NUC-1031 is 625 mg/m2 administered IV on days 1 and 8 in combination with cisplatin (standard dose of 25 mg/m2) (21 day schedule). The dose will be escalated sequentially in cohorts of 3-6 pts using an accelerated titration procedure (725mg/m2, 825mg/m2, 925mg/m2). Treatment will continue until intolerable toxicity/progressive disease. The primary endpoints are safety and RP2D. Secondary endpoints are progression-free survival, OS, response rate and pharmacokinetic endpoints, including assessments of multiple plasma and intracellular analytes: NUC-1031, cisplatin, dFdC, dFdCMP, dFdCDP, dFdCTP and dFdU, and will be correlated with safety profile and clinical activity. Planned accrual is 15-24 pts over 2 years. Cohort 1 has been completed without dose-limiting toxicities. Enrolment to cohort 2 is on-going. Clinical trial information: NCT02351765.

VinCaP: A phase II trial of vinflunine chemotherapy in locally-advanced and metastatic carcinoma of the penis (CRUK/12/021).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 547-547
Author(s):  
Lisa M. Pickering ◽  
Holly Tovey ◽  
Tony Elliott ◽  
Stephanie M. Burnett ◽  
Amit Bahl ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Metastatic Carcinoma ◽  
Primary Analysis ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Exact Design

547 Background: Platinum-based combination chemotherapy regimens are used in the treatment of carcinoma of the penis, but toxicity limits their value for patients with metastatic disease. This trial aims to define both the toxicity and the rate of disease control for the non-platinum cytotoxic agent Vinflunine. Methods: A phase II single-arm trial was designed to demonstrate a clinical benefit rate of at least 40% and to exclude a rate of less than 15% (p0 = 0.15, p1 = 0.40, α = 0.05, β = 0.80, Fleming-A’hern exact design). 22 evaluable patients were required. Key eligibility criteria included measurable, histologically-proven squamous cell carcinoma of the penis staged as M1; or M0, Tx, N3; or M0, Tx, N2 and deemed inoperable by multidisciplinary team; or M0, T4 any N. Patients were required to have ECOG performance status of 0, 1 or 2 and adequate hepatic and renal function. Treatment comprised four 21-day cycles of vinflunine (320mg/m2) with RECIST v1.1 restaging following cycle 4 (response primary endpoint). Patients deemed to be benefitting from treatment were permitted to continue vinflunine at the discretion of the treating clinician until progression or unacceptable toxicity. Results: 25 patients were recruited from 8 UK centres between June 2014 and May 2017. Median age was 68 years; 19 patients had metastatic (M1) disease. All patients have completed trial treatment and primary endpoint assessment. Data cleaning for the primary analysis is currently in progress, with the snapshot for the primary analysis due in October 2017 and primary analysis to be presented to the trial oversight committees in November 2017. Conclusions: It is hoped that single-agent vinflunine will be associated with a favourable toxicity profile combined with meaningful clinical responses. The results will be available for presentation at the meeting. Clinical trial information: NCT02057913.

Phase II Study of Pemetrexed for Second-Line Treatment of Transitional Cell Cancer of the Urothelium

2006 ◽  
Vol 24 (21) ◽  
pp. 3451-3457 ◽  
Author(s):  
Christopher J. Sweeney ◽  
Bruce J. Roth ◽  
Fairooz F. Kabbinavar ◽  
David J. Vaughn ◽  
Michael Arning ◽  
...  
Keyword(s):  
Performance Status ◽  
Cell Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Transitional Cell ◽  
Neoadjuvant Treatment ◽  
Previous Treatment ◽  
Line Treatment ◽  
Second Line ◽  
Grade 3

Purpose To assess the antitumor activity and toxicity of pemetrexed as second-line chemotherapy in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium. Patients and Methods Eligible patients had a performance status of 0 or 1, adequate organ function, previous treatment with one prior chemotherapy regimen for locally advanced or metastatic TCC of the urothelium or relapsed within 1 year of adjuvant or neoadjuvant treatment. Patients received pemetrexed 500 mg/m2 intravenously on day 1 every 21 days, with vitamin B12, folic acid, and dexamethasone prophylaxis. Results Forty-seven patients were enrolled and included in the intent-to-treat efficacy analysis. Responses: 3 (6.4%) complete responses and 10 (21.3%) partial responses produced an overall response rate of 27.7%. Ten patients (21.3%) had stable disease and 22 patients (46.8%) progressed. The median time to progressive disease was 2.9 months (95% CI, 1.7 months to 4.6 months) and median overall survival was 9.6 months (95% CI, 5.1 months to 14.6 months). Median duration of response was 5.0 months (95% CI, 3.9 months to 13.8 months). Of the 47 patients assessable for safety, grade 3 or 4 hematologic events were thrombocytopenia (8.5%; 0.0%), neutropenia (4.3%; 4.3%) and anemia (2.1%; 2.1%), respectively. Nonlaboratory toxicities included grade 4 stomatitis/pharyngitis, sepsis syndrome (one patient each), and grade 3 fatigue (three patients) and diarrhea (two patients). Conclusion Single-agent pemetrexed is safe and active as second-line treatment of patients with advanced TCC of the urothelium. Additional evaluation in the first- or second-line setting in TCC of the urothelium is warranted.

Tolerability of neoadjuvant chemotherapy with gemcitabine plus cisplatin in elderly (older than age 65) patients (pts) with muscle-invasive urothelial cancer.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 296-296
Author(s):  
D. Niedersuess-Beke ◽  
B. Gruenberger ◽  
T. Puntus ◽  
W. Bauer ◽  
M. Lamche ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Performance Status ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Significant Risk ◽  
Palliative Radiotherapy ◽  
Pathologic Response ◽  
Metastatic Setting ◽  
Grade 3 ◽  
Muscle Invasive

296 Background: Urothelial cancer (UC) is a common tumor with a peak in the seventh decade. Locally advanced disease has a significant risk for developing metastases. Neoadjuvant, platinum-containing, combination chemotherapy improves survival over radical cystectomy (RC). Chemotherapy with gemcitabine plus cisplatin (GC) shows equivalent efficacy with less toxicity to methotrexate-vinblastine-doxorubicin- cisplatin (MVAC) in metastatic setting. Methods: We prospectively evaluated 23 elderly pts (8 female, 15 male) with a median age of 72 years, WHO performance status 0/1, with muscle invasive UC who received neoadjuvant GC (gemcitabine 1,000 mg/m2 days 1, 8, 15 and cisplatin 70 mg/m2, day 2 q28) for 3 cycles between 2006 and 2010 prior to RC. Assessments included toxicity of GC, pathologic response, progression free survival (PFS) and overall survival (OS). Results: 21 (91.3%) out of 23 pts finished intended chemotherapy. Two refused chemotherapy due to personal reasons. According to CTCAE guidelines 43.5% developed grade 3 hematologic toxicities; 13% developed grade 4 thrombopenia. Grade 3 non-hematologic toxicities included nausea in 2 patients. In 2 (8.7%) pts grade 4 thromboembolic events occurred. There was no treatment related febrile neutropenia or death. 15 (71.4%) of the pts underwent RC. 5 (23.8%) pts refused RC due to personal reasons. 1 of them agreed second look TURB. 1 patient underwent palliative radiotherapy due to progression of disease. Out of the 16 pts 43.75% achieved pathological response (18.75% pT0 stage and 25% pT1 stage). 56.25% had muscle invasive UC. 18.75% of them nodal positive disease. All 7 pts achieving < pT2 pathologic stage remained progression-free at a median follow up of 16 months. Pts > pT2 stage had a median PFS of 14 months. Median OS was not reached yet. Conclusions: Neoadjuvant GC is a well tolerated regiment in elderly pts and it seems to be less toxic than MVAC. Prophylactic anticoagulation during treatment should be considered. Although pathologic response is lower than in previously published retrospective data we recommend neoadjuvant treatment with GC in elderly pts. [Table: see text]

Safety and efficacy of modified FOLFIRINOX in pancreatic cancer: A retrospective experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14614-e14614 ◽  
Author(s):  
Hemchandra Mahaseth ◽  
John S. Kauh ◽  
Edith Brutcher ◽  
Natalyn Nicole Hawk ◽  
Sungjin Kim ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Emory University ◽  
Grade 3

e14614 Background: Conroy et al reported a significant improvement in overall survival of patients with metastatic pancreatic cancer treated with FOLFIRINOX compared to single agent gemcitabine. The regimen was associated with significant grade 3/ 4 toxicities, such as myelosuppression(46%), fatigue(24%), vomiting(15%) and diarrhea (13%). In order to improve the toxicity profile, we have modified FOLFIRINOX (mFOLFIRINOX) regimen by removing the bolus 5-FU and adding the routine use of growth factor prophylaxis. We present our experience with mFOLFIRINOX in patients with locally advanced or metastatic pancreatic cancer. Methods: After obtaining IRB approval, patients with a diagnosis of pancreatic cancer were identified from the Emory University tumor registry. Twenty eight patients who received at least one dose of mFOLFIRINOX (5-FU 2400 mg/m2 CIVI over 46 hours, leucovorin 400 mg/m2, oxaliplatin 85 mg/m2, irinotecan 180 mg/m2 and pegfilgrastim 6 mg every two weeks ) were selected and their charts were retrospectively reviewed for safety, response, and survival. Results: Of 28 patients, 14 (50%) were male, 18 (64%) white, 8 (29%) black and other 2(7%). Median age was 63 (50-75) and ECOG performance status 0-1. Nineteen (68%) patients had primary tumor located in head of pancreas. Eight patients (29%) experienced grade 3/4 toxicities, i.e., nausea/vomiting (11%), diarrhea (11%), fatigue (11%), neuropathy (4%), neutropenia (4%), thrombocytopenia(4%), and sepsis not-related to neutropenia (4%). No grade 3/4 anemia or febrile neutropenia was noted. mFOLFIRINOX controlled the disease in 20 patients (71%) with 2 CR, 4 PR and 14 SD. With a median follow up of 5.5 months, median overall or progression free survival is not reached. Two patients have died and six patients have progressed. Conclusions: Modified FOLFIRINOX is well tolerated in this US population. The clinical activity appears very promising with majority of patients being free of progression.

Phase I/II study of biweekly pemetrexed plus cisplatin in patients with locally advanced, nonresectable or metastatic urothelial cancer: Safety and efficacy results from phase II.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4550-4550 ◽  
Author(s):  
Ana Lopez Martin ◽  
Joaquim Bellmunt ◽  
José Pablo Maroto ◽  
Enrique Gallardo ◽  
Marta Lopez Brea ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Urothelial Cancer ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Transitional Cell ◽  
Mucosal Inflammation ◽  
Metastatic Urothelial Cancer ◽  
Advanced Urothelial Cancer

4550 Background: Pemetrexed (P) plus cisplatin (C) combination is effective against several malignant tumors. Single-agent P has shown antitumor activity in advanced urothelial cancer; we performed a phase I/II study to define the maximum tolerated dose of biweekly P plus C combination. Here, we report the final results of the phase II study. Methods: Eligible patients (pts) had locally advanced or metastatic transitional cell carcinoma of the urothelium not suitable for curative therapy, performance status (PS) 0-2, estimated life expectancy of at least 12 weeks, and adequate organ function. P and C were administered on days 1 and 15 of each 28-day cycle, up to a maximum of 6 cycles. Pts received the recommended dose from phase I, with P at 400 mg/m2 plus C at 50 mg/m2 (folic acid and vitamin B12 supplementation were also administered). Primary objective was overall response rate (ORR) according to RECIST 1.0. Results: Thirty-eight pts were recruited, 32 (84.2%) pts had bladder cancer with a mean diagnosis time of 1 (range 0-7) year and 30 (78.9%) had metastatic disease; 19 (50%) pts had visceral metastasis and 2 (5.3%) pts had a PS 2. Only 2 pts did receive adjuvant systemic therapy. Median number of cycles was 3 (range 0-7). Twelve (31.6%) pts discontinued the study treatment due to toxicity. The most common treatment-related AEs (> 20%) were asthenia (n=27 pts), nausea and vomiting (n=21, respectively), diarrhea (n=18), anorexia (n=17), mucosal inflammation (n=14), and constipation (n=8). Most treatment-related AEs were of mild or moderate severity. Neutropenia (n=5) and asthenia (n=3) were the most frequent Grade 3 or 4 treatment-related AEs. Serious related AEs were observed in 8 (21.1%) pts. ORR was 39.5% (95% CI 24.0-56.6): 2 (5.3%) pts achieved complete response and 13 (34.2%) pts, partial response. Median progression free survival was 6.7 months, and median overall survival was 10.5 months. Conclusions: In this study, biweekly P (400 mg/m2) plus C (50 mg/m2) combination showed anti-tumor activity in pts with advanced urothelial cancer, with an acceptable safety profile. Clinical trial information: NCT00374868.

Efficacy of Sequential High-Dose Doxorubicin and Ifosfamide Compared With Standard-Dose Doxorubicin in Patients With Advanced Soft Tissue Sarcoma: An Open-Label Randomized Phase II Study of the Spanish Group for Research on Sarcomas

2009 ◽  
Vol 27 (11) ◽  
pp. 1893-1898 ◽  
Author(s):  
Joan Maurel ◽  
Antonio López-Pousa ◽  
Ramón de las Peñas ◽  
Joaquín Fra ◽  
Javier Martín ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Standard Dose ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
High Dose ◽  
Open Label ◽  
Advanced Soft Tissue Sarcoma ◽  
Ecog Performance Status

Purpose To assess the progression-free survival (PFS) and antitumor response to standard-dose doxorubicin compared with sequential dose-dense doxorubicin and ifosfamide in first-line treatment of advanced soft tissue sarcoma. Patients and Methods Patients with measurable advanced soft tissue sarcoma, Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2, between the ages 18 and 65 years, and with adequate bone marrow, liver, and renal function were entered in the study. The stratifications were: ECOG PS (0 v 1), location of metastases, and potentially resectable disease. Patients were randomly assigned to either doxorubicin 75 mg/m2 given as a bolus injection every 3 weeks for 6 cycles (arm A) or doxorubicin at 30 mg/m2 per day for 3 consecutive days once every 2 weeks for 3 cycles followed by ifosfamide at 12.5 g/m2 delivered by continuous infusion over 5 days once every 3 weeks for 3 cycles with filgastrim or pegfilgastrim support (arm B). Results Between December 2003 and September 2007, 132 patients were entered onto the study. Febrile neutropenia, asthenia, and mucositis were more frequent in the arm B. The interim preplanned analysis for futility allowed the premature closure. Objective responses were observed in 23.4% of assessable patients in arm A and 24.1% in arm B. PFS was 26 weeks in the arm A and 24 weeks in arm B (P = .88). Overall survival did not differ between the two therapeutic arms (P = .14). Conclusion Single-agent doxorubicin remains the standard treatment in fit patients with advanced soft tissue sarcoma.

Phase II study of single-agent volasertib (BI 6727) for second-line treatment of urothelial cancer (UC).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 253-253 ◽  
Author(s):  
W. M. Stadler ◽  
D. J. Vaughn ◽  
G. Sonpavde ◽  
N. J. Vogelzang ◽  
S. T. Tagawa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Response Rate ◽  
Single Agent ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Mitotic Checkpoint ◽  
Line Treatment ◽  
Second Line ◽  
Metastatic Urothelial Cancer

253 Background: Polo-like kinase 1 (Plk1) controls multiple essential steps of mitosis. Volasertib (BI 6727) is a first-in-class, selective inhibitor of Plk1. In vitro, Plk1 depletion in cancer cells leads to activation of the mitotic checkpoint, prolonged mitotic arrest, and eventually apoptosis. No standard therapy exists for metastatic urothelial cancer (UC) progressing after initial chemotherapy. Thus, there is an urgent need for novel treatment options. Interim efficacy and tolerability results are presented from an open-label, single-arm, multi-center phase II trial of volasertib in patients (pts) with previously treated advanced UC. Methods: Pts progressing after one prior systemic chemotherapy for locally advanced or metastatic UC or relapsing within 2 years of adjuvant/ neoadjuvant treatment received 300 mg volasertib (2-hour intravenous infusion) on day 1 every 21 days. If well tolerated, dose escalation to 350 mg in cycle 2 was encouraged. Primary endpoint was objective tumor response, defined by RECIST. The trial follows a modified Gehan-two-stage design with an early stopping rule based on the observed response rate of the first 20 pts receiving up to 4 courses of treatment. A minimum response rate of 10% (2/20) was required to recommend additional study. Results: This trial is ongoing: 31 pts (median age 67) were treated between December 2009 and August 2010. All pts were eligible for interim safety/efficacy analysis. As of August 2010, 6 pts (19%) demonstrated a partial response, 7 pts (23%) had stable disease and 16 (52%) progressed between 3-6 weeks after study initiation. Thirteen (42%) pts remain on trial between 13-41 weeks (median time on trial 5 months) without disease progression. Major grade 3 or 4 adverse events (irrespective of drug relatedness) were neutropenia (10 pts, 32%), thrombocytopenia (7 pts, 23%), anemia (5 pts, 16%), hyponatremia (3 pts, 10%), dehydration (2 pts, 7%), and urinary tract infection (2 pts, 7%). Conclusions: Single-agent volasertib was well tolerated and demonstrates clinical activity in the second-line treatment of pts with advanced UC. The early signs of clinical benefit allows proceeding per protocol to the second stage of the trial. [Table: see text]

A phase III randomized trial of two cisplatin-based concurrent chemoradiation (CCRT) regimens for locally advanced head and neck squamous cell carcinoma (LAHNSCC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6035-6035
Author(s):  
Cristina P. Rodriguez ◽  
David J. Adelstein ◽  
Lisa A. Rybicki ◽  
Panayiotis Savvides ◽  
Jerrold P. Saxton ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Feeding Tube ◽  
Concurrent Chemotherapy ◽  
Phase Iii ◽  
Radiation Dermatitis ◽  
Ecog Performance Status ◽  
Hpv Status

6035 Background: Excellent outcomes have been reported using both single and multiagent CCRT in LAHNSCC. This trial compares a 5FU/cisplatin regimen to single agent cisplatin CCRT. Methods: Patients (pts) with previously untreated stage III-IV, M0, LAHNSCC of the larynx, oropharynx (OP), oral cavity or hypopharynx received definitive once or twice daily radiation (70-74.4 Gy) and were randomized between concurrent chemotherapy with either Arm A: cisplatin 100mg/m2 on days 1, 22 and 43 or Arm B: cisplatin (20mg/m2/day) and 5-FU (1000mg/m2/day) as continuous 96 hour infusions weeks 1 and 4. ECOG performance status ≤ 1, and adequate renal, liver and marrow function were required for entry. The primary endpoint was recurrence free survival (RFS). Results: Between 2/2008 and 10/2011, 69 pts were enrolled. An accrual of 126 pts was planned in order to demonstrate an improvement in 2-year RFS from 55% to 75%. The study was closed prematurely when a scheduled interim analysis confirmed markedly better outcomes in both arms and the futility of further comparison. Pt and tumor characteristics were well balanced in both arms. OP cancer was diagnosed in 83% of pts; 86% of the OP cancers were HPV/p16+. With a median follow up of 29.4 months, 2 yr Kaplan-Meier outcome estimates were similar between arms (Table). Pts on Arm A experienced more nephrotoxicity (26% vs. 3%; p=0.007) and ototoxicity (11% vs. 0%; p=0.042), but less Grade ≥2 radiation dermatitis (43% vs. 68%; p=0.038), neutropenia <1000/mm3 (34% vs. 65%; p=0.012), and unplanned hospitalization (43% vs. 68% p=0.038). Treatment outcomes were inferior and feeding tube requirements greater in the HPV/p16 negative and actively smoking pts. Conclusions: Although these CCRT regimens produced similar outcomes, their toxicity profiles proved different and may serve to inform individual pt treatment. Tobacco use and HPV status had far greater impact on treatment outcomes than did the CCRT regimen. Clinical trial information: NCT00608205. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document