A randomized phase II/III study of naptumomab estafenatox plus IFN-α versus IFN-α in advanced renal cell carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3073-3073 ◽  
Author(s):  
Robert E. Hawkins ◽  
Martin Eric Gore ◽  
Yaroslav Shparyk ◽  
Vladimir Bondar ◽  
Oleg Gladkov ◽  
...  
Keyword(s):  
Clin Oncol ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase 1 ◽  
Risk Scores ◽  
Open Label ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
To Receive

3073 Background: Naptumomab estafenatox/ANYARA (Nap) is a fusion protein of an antibody (5T4) and a superantigen (SEA/E-120). After phase I studies (Borghaei. J Clin Oncol. 2009, 27:4116) a prospective, randomized phase II/III trial of Nap + IFN-α (A) vs IFN-α (I) was conducted. Methods: Patients (pts) with RCC were randomized in an open label study to receive A or I. The primary endpoint was OS. Secondary endpoints were PFS, response rate and safety. Baseline (bl) plasma IL-6 was predictive of pazopanib (Tran. Lancet Oncol. 2012, 13:827) and MVA-5T4 vaccine (Harrop. Cancer Immunol Immunother. 2012, 61:2283) benefit in RCC pts. IL-6 and anti-SEA/E-120 antibodies (a-S) were analyzed. A subgroup SG1 had bl levels below median for IL-6 (<7 pg/ml) and a-S. Another subgroup SG2 had IL-6 below 13 pg/ml (Tran. Lancet Oncol. 2012, 13:827) and excluding upper quartile of a-S according to phase 1 levels (Borghaei. J Clin Oncol. 2009, 27:4116). Results: From 5/2007 to 10/2010 513 pts were treated (ITT) with a median follow-up time for censored pts of 43 months. Unexpectedly, pts in certain territories had increased bl a-S (median of 61 pmol/ml in Russia vs 34 in UK). The table summarizes efficacy results. The primary endpoint was not met. Multivariate analysis adjusted for risk scores and subsequent TKI usage verified Nap benefit in pts with low IL-6 and normal a-S. Nap was well tolerated. Pyrexia (A:46%/I:18%), nausea (21%/11%), back pain (18%/6%), vomiting (16%/7%) and chills (12%/4%) were more common after Nap. Conclusions: The study did not meet primary endpoint. In pts with low IL-6 and normal levels of a-S, addition of Nap to IFN-α improves OS and PFS. The results warrant further studies with Nap in sequence or combo with e.g. TKIs in this subgroup. More generally, as bl IL-6 appears to be prognostic and predictive of outcome on treatment with TKIs and immunotherapies this may be a stratification factor for RCC studies. Clinical trial information: NCT00420888. [Table: see text]

Short Course Radiotherapy Concomitant with Temozolomide in GBM Patients: A Phase II Study

2017 ◽  
Vol 103 (5) ◽  
pp. 457-463 ◽  
Author(s):  
Laura Fariselli ◽  
Lucia Cuppini ◽  
Paola Gaviani ◽  
Marcello Marchetti ◽  
Valentina Pinzi ◽  
...  
Keyword(s):  
Total Dose ◽  
Phase Ii ◽  
Local Control ◽  
Primary Endpoint ◽  
Phase Ii Study ◽  
Treatment Schedule ◽  
Open Label ◽  
Macdonald Criteria ◽  
Secondary Endpoints ◽  
Group B

Purpose Despite recent advances, the prognosis of glioblastoma (GBM) remains poor. The aim of this study was to assess the efficacy and tolerability of multiple daily fraction radiotherapy performed with multiple temozolomide (TMZ) administrations in newly diagnosed patients with GBM. Methods This trial was a prospective, open-label, monocentric, nonrandomized, single arm, phase II study. The primary endpoint was the proportion of progression-free patients at 12 months, and the secondary endpoints were overall survival (OS) and toxicity. Thirty-five patients underwent two radiotherapy courses concomitant with TMZ after surgery. At each course, radiation was delivered 3 times daily, 2 Gy/fraction, for 5 consecutive days, and the total dose was 60 Gy; concurrent TMZ was administered in a total dose of 150-200 mg/m2/day. Results The primary endpoint failed to be applied; Macdonald criteria could be used in 16 (46%) patients with local or intracerebral recurrence (group A). In 12 patients, due to suspicion of radiation necrosis vs recurrence, Macdonald criteria were not applied (group B). The OS was 22 months, and OS probabilities at 12, 18, and 24 months were 82%, 59%, and 44%, respectively. Hematologic toxicities generally did not exceed grade 2. The quality of life and cognitive functioning did not significantly change between baseline and the first follow-up. In the multivariate analysis, necrosis and pseudoprogression were significant prognostic factors of OS. Conclusions To improve local control and OS, a more aggressive treatment schedule should be explored. The related higher necrosis risk and its implications regarding local control deserve further investigation.

scholarly journals Oral levosimendan in amyotrophic lateral sclerosis: a phase II multicentre, randomised, double-blind, placebo-controlled trial

2019 ◽  
Vol 90 (10) ◽  
pp. 1165-1170 ◽  
Author(s):  
Ammar Al-Chalabi ◽  
Pamela Shaw ◽  
P Nigel Leigh ◽  
Leonard van den Berg ◽  
Orla Hardiman ◽  
...  
Keyword(s):  
Heart Rate ◽  
Amyotrophic Lateral Sclerosis ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Iii ◽  
Open Label ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Lateral Sclerosis

ObjectiveTo evaluate the efficacy and safety of oral levosimendan in patients with amyotrophic lateral sclerosis (ALS). This phase II, randomised, double-blind, placebo-controlled, crossover, three-period study with 6 months open-label follow-up enrolled adults with ALS and sitting slow vital capacity (SVC) 60%–90 % of predicted from 11 sites in four countries.MethodsPatients received levosimendan 1 mg daily, 1 mg two times a day or placebo during three 14-day crossover periods and levosimendan 1–2 mg daily during open-label follow-up. Primary endpoint was sitting SVC; secondary endpoints included supine SVC, ALS Functional Rating Scale-Revised (ALSFRS-R), tolerability and safety.ResultsOf 66 patients randomised, 59 contributed to the double-blind results and 50 entered open-label follow-up. Sitting SVC was not significantly different between the treatments. In post hoc analysis using period-wise baselines, supine SVC favoured levosimendan over placebo, estimated mean differences from baseline being −3.62% on placebo, +0.77% on levosimendan 1 mg daily (p=0.018) and +2.38% on 1 mg two times a day (p=0.001). Headache occurred in 16.7% of patients during levosimendan 1 mg daily (p=0.030), 28.6% during 1 mg two times a day (p=0.002) and 3.3% during placebo. The respective frequencies for increased heart rate were 5.1% (p=0.337), 18.5% (p=0.018) and 1.7%. No significant differences between the treatments were seen for other adverse events.ConclusionsLevosimendan did not achieve the primary endpoint of improving sitting SVC in ALS. Headache and increased heart rate were increased on levosimendan, although it was otherwise well tolerated. A phase III study to evaluate the longer term effects of oral levosimendan in ALS is ongoing.

Gemcitabine and oxaliplatin (GEMOX) alone or in combination with cetuximab as first-line treatment for advanced biliary cancer: Final analysis of a randomized phase II trial (BINGO).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4032-4032 ◽  
Author(s):  
David Malka ◽  
Laetitia Fartoux ◽  
Vanessa Rousseau ◽  
Tanja Trarbach ◽  
Eveline Boucher ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Mutational Analysis ◽  
Metabolic Response ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
First Line ◽  
Open Label ◽  
Randomized Phase Ii

4032 Background: Gemcitabine-platinum chemotherapy (CTx) regimens are widely accepted as first-line standard of care for patients (pts) with advanced biliary cancers (ABC). EGFR overexpression has been observed in ABC, suggesting that the combination with anti-EGFR monoclonal antibodies may be appropriate. Methods: Patients with ABC, WHO performance status (PS) 0-1, and without prior palliative CTx were eligible for this international, open-label, two-stage, non-comparative, randomized phase II trial. Patients received GEMOX (gemcitabine, 1 g/m² [10 mg/m²/min] at day [D]1 + oxaliplatin, 100 mg/m² at D2, arm A) or GEMOX + cetuximab (500 mg/m² at D1 or 2, arm B), every 2 weeks. The primary endpoint was crude 4-month progression-free survival (PFS) rate (H0, <40%; H1, ≥60%; planned sample size, 100 pts, increased to 150 pts by amendment to allow subgroup analyses). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), PFS, overall survival (OS), and toxicity (NCI-CTC v3.0). Exploratory endpoints included early metabolic response as assessed by PET at 1 month, and tumor KRAS mutational analysis. Results: From Oct. 2007 to Dec. 2009, we enrolled 150 pts (median age, 62 years; male, 57%; metastatic, 79%; cholangiocarcinoma, 84%; median follow-up, 30 months) (Table). Conclusions: GEMOX-cetuximab regimen was well tolerated and met its primary endpoint (4-month PFS ≥60%). However, median PFS and OS were similar in both arms. Exploratory analyses (e.g., KRAS tumor status) are underway to identify pt subgroups deriving benefit from the addition of cetuximab to CTx. [Table: see text]

Randomized, open-label, phase II study comparing five-weekly S-1 plus cisplatin (SP) with tri-weekly capecitabine plus cisplatin (XP) in chemotherapy-naïve patients with HER2 negative advanced gastric cancer (AGC): OGSG 1105 HERBIS-4A trial.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 102-102
Author(s):  
Atsushi Takeno ◽  
Youichi Makari ◽  
Shunji Endo ◽  
Jin Matsuyama ◽  
Ryohei Kawabata ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Open Label ◽  
Group 13 ◽  
Common Grade ◽  
Open Label Phase ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
To Receive

102 Background: This phase II study aimed to investigate the safety and efficacy of XP compared to SP in the first-line treatment of HER2 negative AGC. Methods: Patients were randomly assigned to receive either SP (S-1 at 40–60 mg twice daily for 21 days plus cisplatin at 60 mg/ m2 on day 8, every 5 weeks) or XP (capecitabine 1,000 mg/m2 twice daily for 14 days plus cisplatin 80 mg/m2 on day 1, every 3 weeks). Primary endpoint was response rate (RR), and secondary endpoints were progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF), and adverse events. Results: 84 eligible patients were randomly assigned to receive SP ( N = 41) or XP ( N = 43). No statistical difference was observed in overall RR between the SP and XP groups [51.2% (95% CI, 35.1% to 67.1%) vs. 53.5% (95% CI, 37.7% to 68.8%), P = 1.000]. Despite not significant, however, SP vs. XP showed a trend toward better PFS [median, 5.9 months vs. 4.1 months; hazard ratio (HR), 0.763; 95% CI, 0.462 to 1.259; P = .284] and OS (median, 13.5 months vs. 10.0 months; HR, 0.776; 95% CI, 0.485 to 1.244; P = .290). This trend in the SP vs. XP comparison was more pronounced in TTF (median, 4.5 months vs. 3.1 months; HR, 0.651; 95% CI, 0.421 to 1.006; P = .052). Common grade 3 to 4 hematological toxicities were neutropenia and anemia (SP group, 23% and 23%; XP group, 35% and 28%). Grade 3-4 anorexia and hyponatremia were more frequently seen in the XP group (31% and 16%) compared to the SP group (13% and 5%). Treatment-related deaths occurred in one patient (2.3%) in the XP group. Conclusions: XP failed to demonstrate the superior efficacy over SP. Higher incidence of severe toxicities by XP suggests SP as the standard 1st line chemotherapy for HER2 negative AGC in Japan. Clinical trial information: UMIN000006755.

Final results and OS of the randomized phase II VOLFI trial (AIO- KRK0109): mFOLFOXIRI + panitumumab versus FOLFOXIRI as first-line treatment in patients with RAS wild- type metastatic colorectal cancer (mCRC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3511-3511 ◽  
Author(s):  
Michael Geissler ◽  
Jorge Riera-Knorrenschild ◽  
Uwe Marc Martens ◽  
Swantje Held ◽  
Jobst Greeve ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Objective Response ◽  
Open Label ◽  
Secondary Resection ◽  
Strong Trend ◽  
Mutational Status ◽  
Secondary Endpoints

3511 Background: This trial evaluated activity and safety of mFOLFOXIRI + panitumumab vs FOLFOXIRI in ECOG 0-1, primarily non-resectable mCRC patients. The final primary endpoint was presented at ASCO and ESMO 2018. Now we report for the first time the final results regarding OS and PFS. Methods: Prospective 2:1 randomized, controlled, open label multi-center, phase II trial comparing mFOLFOXIRI (Ox 85 mg/m2, Iri 150 mg/m2, 5-FU 3000mg/m2 cont. 48h, LV 200 mg/m2) + Panitumumab 6 mg/KG (arm A) with FOLFOXIRI (Ox 85 mg/m2, Iri 165 mg/m2, 5-FU 3200mg/m2 cont. 48h, LV 200 mg/m2; arm B), both arms q2w. Prospective strata were cohort 1: irresectable mCRC (n=65), and cohort 2: chance of secondary resection of metastatic lesions (n=31). Primary endpoint was ORR, secondary endpoints were secondary resection rate (cohort 2), DCR, PFS, OS, toxicity, quality of life (QLQ-C30). Financially supported by an unrestricted grant from Amgen. Results: A total of 96 patients were randomized (63 arm A, 33 arm B). ORR was 87.3% in arm A and 60.6% in arm B (p=0.0041, OR 4.47; 95%-CI 1.614-12.376). Secondary resections of metastases in the ITT population were observed in 33·3% (arm A Pmab) versus 12·1% (arm B) (OR=3.63; 95%-CI 1.13–11.67, p=0·029) and in cohort 2 in 75% (arm A Pmab) versus 36.4% (arm B) (OR=5.25; 95%-CI 1.07–25.8, p=0.05), respectively. Median PFS was similar in the study arms (9.7 mo in both arms, HR 1.071; 95%-CI 0.689-1.665, p=0.76). OS in the ITT population showed a strong trend in favour of the Pmab-containing arm A with a median OS of 35.7 mo compared to 29.8 mo in arm B (HR: 0·67; 95%-CI 0.41-1.11, P=0·12). mOS of cohort 2 was 52.0 mo in arm A versus 41.7 mo in arm B (HR 0.413; 95%-CI 0.15-1.12, p=0.07). Further results regarding to sidedness and BRAF mutational status will be presented. Conclusions: The addition of Pmab to a mFOLFOXIRI regimen in patients with RASwildtype metastatic colorectal cancer significantly improved objective response rate and the rate of secondary resection of metastases. Although PFS was comparable, there was a strong trend towards improved OS in the Pmab arm. Future studies are warranted to confirm this trend towards improved overall survival with this regimen. Clinical trial information: NCT01328171.

Neoadjuvant atezolizumab (A) with gemcitabine and cisplatin (GC) in patients (pts) with muscle-invasive bladder cancer (MIBC): A multicenter, single-arm, phase 2 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4517-4517
Author(s):  
Samuel Aaron Funt ◽  
Michael Lattanzi ◽  
Karissa Whiting ◽  
Hikmat A. Al-Ahmadie ◽  
Colleen Quinlan ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Pancreatic Enzyme ◽  
Phase 2 Trial ◽  
Common Grade ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Muscle Invasive ◽  
Enzyme Elevation ◽  
To Receive

4517 Background: Neoadjuvant GC is standard for pts with MIBC and can result in pathologic downstaging to non-MIBC ( < pT2N0) at radical cystectomy (RC), which correlates with improved survival. Based on the known activity of A in metastatic BC (mBC), we tested the combination of GC+A as neoadjuvant therapy for MIBC in a phase II trial (NCT02989584). Methods: Eligible pts with MIBC (cT2-T4aN0M0) received a single dose of A (1200 mg IV) and, two weeks later, began C (as either 70mg/m2 IV on D1 or 35 mg/m2 on D1,D8), G (1000 mg/m2 on D1,D8), and A (1200 mg IV on D8) every 21 days for 4 cycles followed by RC. Pts were also able to receive one additional dose of A 3 weeks after the last dose of A and prior to RC. The primary endpoint was proportion of pts with < pT2N0. Pts were considered not evaluable for the primary endpoint if they received less than 2 cycles due to withdrawal of consent or unrelated adverse events (AEs). Secondary endpoints included the proportion of pts with pT0N0, recurrence-free survival (RFS), and safety. We prespecified null and alternate < pT2N0 rates of 35% and 55%, respectively, with the null being rejected if at least 19 of 39 pts achieved < pT2N0. Pretreatment tumors underwent centralized PD-L1 staining (SP142; positive if ≥5% of immune cells). Results: Between Feb 2018 and May 2020, 44 pts were enrolled from five institutions. Five pts were not evaluable (withdrawal of consent before C3, n = 4; unrelated AEs during C1, n = 1). Of the 39 evaluable pts (cT2N0 79%, cT3N0 18%, cT4N0 3%), 1 pt refused surgery and was considered a non-responder. The primary endpoint was met, with 27 of 39 pts (69%) < pT2N0 at RC, including 15 (38%) pT0N0. All pts achieving < pT2N0 are alive and disease free. The median RFS was not reached with a median follow-up of 16.7 months (range: 7.7-33.2). The median time from last dose of chemotherapy to RC was 7.8 weeks (range 5.1 – 17). The most common grade 3-4 treatment related AEs were due to chemotherapy and were neutropenia (36%), lymphopenia (16%), and anemia (11%). Possible grade 3-4 immune related AEs included 2 pts with asymptomatic grade 3 pancreatic enzyme elevation, 1 pt with grade 3 pancreatitis, and 1 pt with hepatitis requiring steroids. Only 4 of 39 (10%) pts had PD-L1 positive tumors, which is low compared to mBC (25% positive; Powles et al. Lancet 2017) and MIBC (40% positive; Powles et al. Nature Med 2019) cohorts also tested with the SP142 clone. All 4 pts with PD-L1 positive tumors achieved < pT2N0. Twelve of 12 (100%) non-responding pts were PD-L1 negative and 23 of 27 (85%) responding pts were PD-L1 negative (p = 0.3). Conclusions: Neoadjuvant GC+A is an effective and safe regimen for the treatment of pts with MIBC. The PD-L1 positivity rate was low compared with other studies and was not predictive of pathologic downstaging. Additional interrogation of the genomic and host immune factors mediating response and resistance to GC+A is ongoing. Clinical trial information: NCT02989584.

A randomized phase II study evaluating the activity of bevacizumab in combination with carboplatin plus paclitaxel in patients with previously untreated advanced mucosal melanoma (NCT02023710).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9521-9521
Author(s):  
Xieqiao Yan ◽  
Xinan Sheng ◽  
Lu Si ◽  
Zhihong Chi ◽  
Chuanliang Cui ◽  
...  
Keyword(s):  
Disease Control ◽  
Phase Ii ◽  
Cox Model ◽  
Mucosal Melanoma ◽  
Phase Iii ◽  
Study Endpoint ◽  
Primary Study ◽  
Open Label ◽  
Randomized Phase Ii ◽  
To Receive

9521 Background: Mucosal melanoma is rare and associated with extremely poor prognosis. There was no standard treatment for advanced mucosal melanoma patients. BEAM study had demonstrated the effectivity and safety of bevacizumab combined with carboplatin plus paclitaxel in patients with previously untreated metastatic melanoma. This study was to evaluate the activity of bevacizumab combined with carboplatin plus paclitaxel in Patients with Previously Untreated Advanced Mucosal Melanoma. Methods: This study is an open-label, multicenter, randomized phase II trial. Eligible patients had metastatic, recurrent, or unresectable mucosal melanoma and no received any systemic therapy before enrollment. Patients were randomly allocated in a 2:1 ratio to receive bevacizumab (CPB arm, 5mg/kg every two weeks) or placebo (CP arm) with carboplatin (area under the curve, 5) plus paclitaxel (175 mg/m2). Treatment was continued for both groups until disease progression, unacceptable toxicity, death, or withdrawal of consent. The primary study endpoint is progress-free survival (PFS). Overall survival, disease control rate, and safety will also be assessed. Results: The first patient visit was December 1st, 2013, and the final data cutoff was August 30th, 2018. At that time, 114 patients were randomly assigned to receive CP or CPB therapy. Median PFS was 3.2 months for the CP arm and 4.7 months for the CPB arm (HR, 0.50; 95% CI, 0.33-0.72; P = 0.001). Median OS was 9.0 months in the CP arm versus 12.9 months in the CPB arm (HR, 0.61; 95% CI, 0.40-0.92; P = 0.02). The PFS was longer in the CPB arm in the subgroups of patients with neutrophil-to-lymphocyte ratio (NLR) more than 4 and patients with abnormal lactate dehydrogenase concentration (1.2 v 3.0 months, HR, 0.38; 2.0 v 4.7 months, HR, 0.39, respectively). Multivariate analysis using the Cox model showed that combination with bevacizumab was the predictor for better disease control and survival (PFS: HR 0.400, 95% CI 0.251-0.636, P < 0.001; OS: HR 0.505, 95% CI 0.313-0.814, P = 0.005). No new safety signals were observed. Conclusions: To our knowledge this is the largest study about advanced mucosal melanoma. This study demonstrated that bevacizumab in combination with carboplatin plus paclitaxel is active and safe regimen as first line treatment in patients with in advanced mucosal melanoma. A phase III study will be necessary to confirm the benefit, especially in some special setting such as elevated NLR and elevated LDH subgroups. Clinical trial information: NCT02023710.

Sequential chemoradiotherapy (SCRT) for larynx preservation (LP): Preliminary results of the randomized phase II TREMPLIN study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6010-6010 ◽  
Author(s):  
J. Lefebvre ◽  
Y. Pointreau ◽  
F. Rolland ◽  
M. Alfonsi ◽  
A. Baudoux ◽  
...  
Keyword(s):  
Phase Ii ◽  
Concurrent Chemoradiotherapy ◽  
New Approach ◽  
Larynx Preservation ◽  
Randomized Phase Ii ◽  
Significant Difference ◽  
Secondary Endpoints ◽  
Function Preservation ◽  
To Receive

6010 Background: Induction chemotherapy (ICT) followed by irradiation (RT) and concurrent chemoradiotherapy (CRT) are validated options for LP. Docetaxel-based ICT, concurrent cetuximab and RT are new options and SCRT (ICT followed by CRT) has been reported as a potential new approach. However, to date there are no data assessing SCRT specifically for LP. Methods: Previously untreated patients (pts) with larynx or hypopharynx squamous cell carcinoma and candidates for a total laryngectomy were eligible for this randomized phase II study. Eligible pts received 3 cycles of ICT (docetaxel and cisplatin both 75 mg/m2 on day 1 and 5-FU 750 mg/m2/day on days 1–5). In case of response ≥ 50 % pts were randomized to receive either in arm A: RT (70 Gy) with cisplatin (100 mg/m2 on days 1, 22 and 43 of RT) or in arm B: Cetuximab (400 mg/m2 loading dose before RT and 250 mg/m2 on the first day of the 7 weeks of RT. Pts with response < 50% had salvage surgery. Primary endpoint was LP 3 months after treatment, secondary endpoints were larynx function preservation at 18 months, quality of function and tolerance to treatment. Results: From March 2006 to April 2008 (end of accrual), 153 pts with stage III-IV larynx/hypopharynx cancer were enrolled in the study and could start ICT. Of them 74 % could receive the planned ICT while the others had either reduced dosages or less than 3 cycles. Toxic deaths occurred in 3 pts (2%). Of the 147 evaluable pts after ICT, 22 were non-responders (15%), 4 pts were withdrawn from the study, 6 responding pts with ICT-related toxicity precluding any further cisplatin could not be randomized and finally 115 pts could be randomized (59 in arm A and 56 in arm B). 3 months after treatment there was no significant difference in LP (93% in arm A and 96% in arm B). In arm A, 45 % of pts could receive the full CRT protocol vs 71 % in arm B. In arm A 50% of pts had cisplatin-related toxicity (definitive in 52% the cases) while in arm B 26 % of patients had cetuximab-related toxicity (definitive in only 1 case). There was no CRT treatment-related death. Conclusions: SCRT is considered for LP. ICT followed by RT with concurrent cetuximab appeared better tolerated than with concurrent cisplatin with the same LP rate 3 months after treatment. [Table: see text]

Randomized phase II study of cladribine with simultaneous or delayed rituximab in patients with untreated hairy cell leukemia.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7003-7003 ◽  
Author(s):  
Dai Chihara ◽  
Evgeny Arons ◽  
Maryalice Stetler-Stevenson ◽  
Constance Yuan ◽  
Hong Zhou ◽  
...  
Keyword(s):  
Phase Ii ◽  
Hairy Cell Leukemia ◽  
Residual Disease ◽  
Single Agent ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Secondary Endpoints

7003 Background: Single-agent purine analog therapy, usually cladribine, has been the standard 1st-line therapy of hairy cell leukemia (HCL) for ~30 years. Relapse is attributed to minimal residual disease (MRD) persisting despite complete remission (CR). Rituximab can clear MRD, but there are no long-term data for how frequently and for how long this happens, or even how frequently MRD remains after cladribine. We therefore conducted a randomized phase II trial of 1st-line cladribine with concurrent vs delayed rituximab. Methods: The primary endpoint was to determine if 8 weekly doses of rituximab (375 mg/m2 iv) begun the same day as 5 daily doses of cladribine (0.15 mg/kg iv) reduce HCL MRD 6 months later compared to cladribine alone. Secondary endpoints included testing delayed rituximab, 8 weekly doses beginning if/when MRD is detected in blood (or if HCL-related cytopenias persist preventing consideration of CR) ≥ 6 months after cladribine. Both groups could receive a 2nd course of rituximab if the same situation recurred ≥ 6 months after starting the 1st course of rituximab. MRD was assessed in blood (PB) and bone marrow (BM) using flow cytometry (FC), consensus PCR, and immunohistochemistry. Results: Sixty-eight patients were randomized 1:1 to concurrent vs delayed arms. At 6 months after cladribine, 97% concurrent vs 24% delayed (p < 0.0001) patients were MRD-free by all tests. 100% concurrent vs 41% delayed patients were MRD-free by all tests except BMA FC (p < 0.0001). At a median follow-up of 87.3 months, delayed rituximab was required by 1 concurrent patient vs 27 courses in 21 delayed patients. MRD-free survival after 1st rituximab was not reached for 34 patients after concurrent rituximab, with 32 still MRD-free after a median of 72 months (94% MRD-free survival), compared to median MRD-free survival 60.1 months after delayed rituximab, with 10 (48%) of 21 remaining MRD-free (p < 0.0001, hazard ratio for concurrent rituximab 0.09). Conclusions: Achievement of MRD-free CR after 1st line cladribine for HCL is greatly enhanced by concurrent rituximab. Use of delayed rather than concurrent rituximab could achieve MRD-free CR but durability was clearly inferior to concurrent rituximab. Longer follow-up will determine if MRD-free survival leads to cures of HCL, increased CR duration, and/or less need for additional therapy. Clinical trial information: NCT00923013.

Induction oxaliplatin capecitabine followed by switch to carboplatin-paclitaxel based RT versus continuing oxaliplatin capecitabine RT in operable esophageal adenocarcinoma: Survival analysis of the randomized phase II neoscope trial.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 373-373
Author(s):  
Somnath Mukherjee ◽  
Chris Hurt ◽  
Catrin Cox ◽  
Ganesh Radhakrishna ◽  
Sarah Gwynne ◽  
...  
Keyword(s):  
Phase Ii ◽  
Complete Response ◽  
Oesophageal Adenocarcinoma ◽  
Oesophagogastric Junction ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Initial Results ◽  
Term Analysis ◽  
Clinical Trial Information

373 Background: Initial results of the NEOSCOPE trial comparing pre-operative CarPac vs OxCap based chemoradiotherapy (CRT) in patients with adenocarcinoma of the oesophagus or oesophagogastric junction showed comparable toxicity and improvement in pathological complete response (pCR) in favour of the CarPacRT. Here we report survival after a median follow-up of 40.7 months (95% CI: 45.1-53.6). Methods: NEOSCOPE was an open, randomised, ‘pick a winner’ phase II trial. Patients with resectable oesophageal adenocarcinoma ≥ cT3 and/or ≥ cN1 were randomised to OxCapRT (oxaliplatin 85 mg/m2 day 1, 15, 29; capecitabine 625 mg/m2 bd on days of RT) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m2 day 1, 8, 15, 22, 29). RT dose was 45 Gy/25 fractions/5 weeks. Induction OxCap (2 cycles) was given prior to CRT. Surgery was performed 6–8 weeks after CRT.The primary endpoint was pCR, secondary endpoints were toxicity, PFS and OS. Results: Between Oct 2013 and Feb 2015, 85 patients were recruited from 17 UK centres. Median OS was not reached in the CarPacRT group and was 41.72 months (95% CI 19.58-.)in the OxCap group (HR 0.56[95% CI 0.29-1.07]; p=0.079). 3-year and 5-year OS rates were 74% (95% CI 58%-85%) and 54% (95% CI 34%-71%) (CarPacRT), and 52% (95% CI 35%-67%) and 39% (95% CI 21%-56%) (OxCapRT). Median PFS (not reached vs 35.3 months, HR=0.61 [95% CI 0.33-1.12]; p=0.111) and metastatic PFS (not reached vs 39.0 months, HR=0.61 [95% CI 0.32-1.14], p=0.118) both favoured the CarPacRT arm. Local recurrence rate was low (OxCapRT= 10%; CarPacRT= 7%). The OS benefit for CarPacRT was consistent across subgroups but not statistically significant. Conclusions: In this longer term analysis there was some evidence that induction OxCap followed by switch to CarPacRT was superior to continuing OxCapRT, with efficacy similar to that seen in other published studies such as ‘CROSS’ and ‘FLOT’. Taken together with the previously published pCR results CarPacRT rather than OxCapRT warrants inclusion in future trials. Funding: Cancer Research UK (C44694/A14614). Clinical trial information: NCT01843829.

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