Final report of a randomized phase II study of docetaxel/oxaliplatin (DO) and docetaxel (D) in previously treated non-small cell lung cancer (NSCLC) patients (pts). A novel design, Alpe-Adria Thoracic Oncology Multidisciplinary group study (ATOM 019)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19010-e19010
Author(s):  
O. Belvedere ◽  
A. Follador ◽  
C. Rossetto ◽  
A. M. Sibau ◽  
C. Defferrari ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Trial Design ◽  
Phase Ii Trial ◽  
Phase Iii ◽  
Cross Resistance ◽  
Line Therapy ◽  
Randomized Phase Ii ◽  
Platinum Based Chemotherapy ◽  
Previously Treated

e19010 Background: No combination regimen has proven superior to single agent chemotherapy as 2nd-line treatment for NSCLC. The absence of cross-resistance with cisplatin/carboplatin, favorable toxicity profile, along with both pre-clinical and clinical evidence of activity make O a good candidate for combination with D as 2nd-line therapy of NSCLC. We evaluated the activity of DO in this setting using a novel phase II trial design. Methods: This multicenter, non-comparative randomized phase II trial evaluated the activity of D (75 mg/m2 d1) and O (70 mg/m2 d2) every 3 weeks in previously treated NSCLC pts; the comparator arm was D (75 mg/m2 d1 every 3 weeks). This one-stage, three-outcome phase II trial design (Sargent, Control Clin Trials 2001) had 21 evaluable pts/arm. All had histologically confirmed NSCLC that progressed during/after platinum-based chemotherapy. Primary endpoint was response rate; secondary endpoints were toxicity, time to progression (TTP), 1-yr survival. Results: Fifty pts were enrolled. Pts characteristics: M/F, 76/24%; median age 62 yrs (range 43–69); ECOG PS 0/1, 36/64%; adenocarcinoma/other, 36/64%. With 48 pts evaluable, partial response was seen in 20% and 8% of pts; stable disease in 52% and 32% and progressive disease in 24% and 56% for DO and D, respectively; 1 pt was inevaluable due to early death (D arm). Main grade 3–4 toxicities were: neutropenia 56% and 64%; febrile neutropenia 4% and 8%; diarrhea 12% and 4% for DO and D, respectively. Median TTP was 4.9 and 1.8 months, median survival 10.9 and 6.9 months, and 1-yr survival 41% and 16% for DO and D, respectively. Conclusions: This study shows how novel phase II trial designs enrolling a limited number of pts may help identify promising regimens for subsequent study in phase III trials. The level of activity for DO we observed satisfied the pre-defined study primary endpoint and warrants further evaluation of this combination as 2nd-line therapy for NSCLC. Protocol developed at the 6th FECS/AACR/ASCO Workshop on Methods in Clinical Cancer Research, Flims 2004, with Professors Marc Buyse and Chris Twelves. [Table: see text]

scholarly journals Randomized Phase II Trial Designs With Biomarkers

2012 ◽  
Vol 30 (26) ◽  
pp. 3304-3309 ◽  
Author(s):  
Boris Freidlin ◽  
Lisa M. McShane ◽  
Mei-Yin C. Polley ◽  
Edward L. Korn
Keyword(s):  
Phase Ii ◽  
Trial Design ◽  
Phase Ii Trial ◽  
Phase Iii ◽  
Published Data ◽  
Phase Ii Trials ◽  
Phase Iii Trial ◽  
New Therapy ◽  
Randomized Phase Ii ◽  
Enrichment Designs

Efficient development of targeted therapies that may only benefit a fraction of patients requires clinical trial designs that use biomarkers to identify sensitive subpopulations. Various randomized phase III trial designs have been proposed for definitive evaluation of new targeted treatments and their associated biomarkers (eg, enrichment designs and biomarker-stratified designs). Before proceeding to phase III, randomized phase II trials are often used to decide whether the new therapy warrants phase III testing. In the presence of a putative biomarker, the phase II trial should also provide information as to what type of biomarker phase III trial is appropriate. A randomized phase II biomarker trial design is proposed, which, after completion, recommends the type of phase III trial to be used for the definitive testing of the therapy and the biomarker. The recommendations include the possibility of proceeding to a randomized phase III of the new therapy with or without using the biomarker and also the possibility of not testing the new therapy further. Evaluations of the proposed trial design using simulations and published data demonstrate that it works well in providing recommendations for phase III trial design.

Results of a phase II trial of single-agent amrubicin (AMR) in patients with extensive disease small cell lung cancer (ED-SCLC) refractory to first-line platinum-based chemotherapy: An update

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8103-8103
Author(s):  
D. S. Ettinger ◽  
R. Jotte ◽  
P. Lorigan ◽  
V. Gupta ◽  
L. Garbo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Treatment Completion ◽  
First Line ◽  
Line Therapy ◽  
Platinum Based Chemotherapy ◽  
Line Chemotherapy

8103 Background: Amrubicin (AMR), a third-generation synthetic anthracycline and potent topoisomerase II inhibitor, is approved in Japan for the treatment of lung cancer. Patients (pts) with SCLC, who are refractory to first-line chemotherapy or progress within 3 months (mos) of treatment completion, are less likely to respond to additional chemotherapy and have an expected median survival of 3–5 mos. Here, we investigate the efficacy and safety of single-agent AMR in the treatment of Western pts with refractory ED-SCLC. Methods: In this phase II trial, pts with ED-SCLC refractory to prior 1st-line platinum-based chemotherapy (defined as progression (PD) while on therapy or relapse within 90 days of treatment completion) and ECOG performance status (PS) ≤2 were eligible. Patients were treated with intravenous AMR 40 mg/m2/day x 3 days every 21 days until PD or intolerable toxicity. The primary endpoint was response rate (ORR, by RECIST), with a goal to demonstrate an ORR ≥18% (point estimate). Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results: In all, 75 pts were enrolled with a median age of 63 years (range 43–88), 52% female, 17% PS 2. Response to 1st-line therapy was 5% complete remission (CR), 36% partial remission (PR) and 28% PD. Median time from completion of 1st-line therapy to PD was 1.3 mos. Sixty-nine pts received AMR for a median of 4 cycles (range 1–12). Six pts died or discontinued before receiving treatment. The primary endpoint was met with an ORR of 21% (16/75, 95% confidence interval [CI] 13.6% - 31.9%), including CR in 1 pt (1%) and PR in 15 pts (20%). Stable disease was achieved in 40% of pts. Two pts with PD as best response to 1st line chemotherapy achieved a PR. Median OS was 6.0 mos (95% CI 4.8–7.1 mos). Median PFS was 3.2 mos (95% CI 2.4–4.0 mos). The most common grade 3 or 4 adverse events were neutropenia (65%), thrombocytopenia (39%), and leukopenia (35%). Seven (10%) patients experienced febrile neutropenia. Dose reductions were required in 26 patients (38%). Conclusions: AMR shows promising activity, with an ORR of 21%, and an acceptable safety profile in patients with refractory ED-SCLC, and warrants further study in these pts. [Table: see text]

Temsirolimus in platinum-resistant metastatic urothelial cancer: A phase II trial.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 302-302
Author(s):  
Holger Gerullis ◽  
Christoph Eimer ◽  
Evangelos Georgas ◽  
Jens Willem Bangner ◽  
Thomas Otto
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Line Therapy ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy ◽  
Grade 3

302 Background: This investigator initiated phase II trial assessed temsirolimus, an inhibitor of mamalian target of rapamycin (mTOR), as second-line therapy in patients with locally advanced or metastatic TCCU after failure of platinum-containing therapy. Methods: 15 patients were enrolledin this phase II trial from June/2009 to June/2011. Primary endpoint was overall survival, as secondary endpoints we defined time to disease progression, safety and QoL along treatment. Patients with progressive TCCU after prior platinum-based chemotherapy received 25 mg of temsirolimus for 8 weeks. Evaluation for response was acomlished every 8 weeks according to the RECIST criteria, QoL assessment was done every 4 weeks using the QLC-C30 questionnaire, adverse events (AEs) were recorded and graded using NCI-CTC criteria. Results: We enrolled 15 patients in this study, of whom 14 (93%) were available for activity and safety assessment. We treated 10 (71%) male and 4 female (29%) patients median age was 64.7 years (45-76). Patients received on average 13 (3-15) infusions of temsirolimus. Median overall survival was 3.5 months (107 days). Median time to disease prgression was 2.5 months. Four patients with transient stable disease were observed. QoL assessment along treatment revealed a reduction of EORTC-QLQ-C30 (Global Health Status-Subscale) from initial 7.86 to 5.00. Temsirolimus was well tolerated, mostly observed were fatigue (Grade 3-4) in 2 patients, pancytopenia (Grade 3-4) in 2 patients, thrombopenia (Grade 3-4) in 2 patients. All other adverse events were grade 1-2 in nature. Conclusions: The primary endpoint was not met with an overall survival of 3.5 montsh only. Therefore the trial was closed after 14 patients. Temsirolimus seems to have poor activity in patients with progressive metastasized TCCU after platinum-containing first-line therapy.

scholarly journals Randomized phase II trial of avelumab alone or in combination with cetuximab for patients with previously treated, locally advanced, or metastatic squamous cell anal carcinoma: the CARACAS study

2021 ◽  
Vol 9 (11) ◽  
pp. e002996
Author(s):  
Sara Lonardi ◽  
Alessandra Anna Prete ◽  
Federica Morano ◽  
Marco Messina ◽  
Vincenzo Formica ◽  
...  
Keyword(s):  
Phase Ii ◽  
Squamous Cell ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Anal Carcinoma ◽  
Open Label ◽  
Egfr Inhibition ◽  
Randomized Phase Ii ◽  
Previously Treated

BackgroundNo standard therapies beyond first line are established for advanced squamous cell anal carcinoma (aSCAC). Earlier preliminary data suggest activity of epidermal growth factor receptor (EGFR) inhibition and programmed cell death ligand (PD-(L))1 blockade in patients with previously treated disease. Aim of this study was to explore activity and safety of avelumab with/without cetuximab in patients with aSCAC.MethodsIn this open-label, non-comparative, ‘pick the winner’, multicenter randomized phase II trial (NCT03944252), patients with aSCAC progressing after one or more lines of treatment were randomized 1:1 to the anti-PD-L1 agent avelumab alone (arm A) or combined with cetuximab (arm B). Overall response rate (ORR) was the primary endpoint. With one-sided α error set at 0.05 and power of 80%, at least 4 responses out of 27 patients per arm had to be observed to declare the study positive. Secondary endpoints were progression free survival (PFS), overall survival (OS), and safety.ResultsThirty patients per arm were enrolled. Three patients in arm A and five in arm B achieved partial response: primary endpoint was reached in combination arm. ORR was 10% (95% CI 2.1 to 26.5) and 17% (95% CI 5.6 to 34.7) in arms A and B; disease control rate was 50% (95% CI 31.3 to 68.7) in arm A and 57 (95% CI 37.4–74.5) in arm B. At a median follow-up of 26.7 months (IQR 26.5–26.9), median PFS was 2.0 months (95% CI 1.8 to 4.0) in arm A and 3.9 (95% CI 2.1 to 5.6) in arm B. Median OS was 13.9 months (95% CI 7.7 to 19.4) in arm A and 7.8 (95% CI 6.2 to 11.2) in arm B. Acceptable safety profile was observed in both arms.ConclusionsCARACAS study met its primary endpoint in arm B, documenting promising activity of dual EGFR and PD-L1 blockade in aSCAC.

Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial

2018 ◽  
Vol 36 (5) ◽  
pp. 446-453 ◽  
Author(s):  
Piet Ost ◽  
Dries Reynders ◽  
Karel Decaestecker ◽  
Valérie Fonteyne ◽  
Nicolaas Lumen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Specific Antigen ◽  
Phase Iii ◽  
Curative Intent ◽  
Free Survival ◽  
Local Progression ◽  
Randomized Phase Ii

Purpose Retrospective studies suggest that metastasis-directed therapy (MDT) for oligorecurrent prostate cancer (PCa) improves progression-free survival. We aimed to assess the benefit of MDT in a randomized phase II trial. Patients and Methods In this multicenter, randomized, phase II study, patients with asymptomatic PCa were eligible if they had had a biochemical recurrence after primary PCa treatment with curative intent, three or fewer extracranial metastatic lesions on choline positron emission tomography–computed tomography, and serum testosterone levels > 50 ng/mL. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions (surgery or stereotactic body radiotherapy). Surveillance was performed with prostate-specific antigen (PSA) follow-up every 3 months, with repeated imaging at PSA progression or clinical suspicion for progression. Random assignment was balanced dynamically on the basis of two factors: PSA doubling time (≤ 3 v > 3 months) and nodal versus non-nodal metastases. The primary end point was androgen deprivation therapy (ADT)–free survival. ADT was started at symptomatic progression, progression to more than three metastases, or local progression of known metastases. Results Between August 2012 and August 2015, 62 patients were enrolled. At a median follow-up time of 3 years (interquartile range, 2.3-3.75 years), the median ADT-free survival was 13 months (80% CI, 12 to 17 months) for the surveillance group and 21 months (80% CI, 14 to 29 months) for the MDT group (hazard ratio, 0.60 [80% CI, 0.40 to 0.90]; log-rank P = .11). Quality of life was similar between arms at baseline and remained comparable at 3-month and 1-year follow-up. Six patients developed grade 1 toxicity in the MDT arm. No grade 2 to 5 toxicity was observed. Conclusion ADT-free survival was longer with MDT than with surveillance alone for oligorecurrent PCa, suggesting that MDT should be explored further in phase III trials.

Sign in / Sign up

Export Citation Format

Share Document