Optimum biased coin designs for sequential clinical trials with prognostic factors

Biometrika ◽  
1982 ◽  
Vol 69 (1) ◽  
pp. 61-67 ◽  
Author(s):  
A. C. ATKINSON
Keyword(s):  
Clinical Trials ◽  
Prognostic Factors ◽  
Biased Coin

scholarly journals Patients with Primary Central Nervous System Lymphoma Not Eligible for Clinical Trials: Prognostic Factors, Treatment and Outcome

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2934
Author(s):  
Sabine Seidel ◽  
Michelle Margold ◽  
Thomas Kowalski ◽  
Alexander Baraniskin ◽  
Roland Schroers ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Prognostic Factors ◽  
Central Nervous System Lymphoma ◽  
Initial Response ◽  
Early Response ◽  
Multicenter Trial ◽  
High Dose ◽  
Therapeutic Trials

Patients with primary central nervous system lymphoma (PCNSL) not fulfilling inclusion criteria for clinical trials represent an underreported population. Thirty-four consecutive PCNSL patients seen at our center between 2005 and 2019 with exclusion criteria for therapeutic trials were analyzed (non-study patients) and compared with patients from the G-PCNSL-SG-1 (German PCNSL Study Group 1) study (study patients), the largest prospective multicenter trial on PCNSL, comprising 551 patients. Median follow up was 68 months (range 1–141) in non-study patients and 51 months (1–105) in study patients. Twenty-seven/34 (79.4%) non-study patients received high dose methotrexate (HDMTX), while seven/34 (20.6%) with a glomerular filtration rate (GFR) < 50 mL/min did not. Median overall survival (OS) was six months (95% confidence interval [CI] 0–21 months) in those 34 non-study patients. The 27 non-study patients treated with HDMTX were compared with 526/551 G-PCNSL-SG-1 study patients who had received HDMTX as well. Median OS was 20 months (95% CI 0–45)/21 months (95% CI 18–25) in 27 non-study/526 study patients (p = 0.766). Favorable prognostic factors in non-study patients were young age, application of HDMTX and early response on magnet resonance imaging (MRI). If HDMTX-based chemotherapy can be applied, long-term disease control is possible even in patients not qualifying for clinical trials. Initial response on early MRI might be useful for decision on treatment continuation.

Prognostic Factors Associated To Achievement Of Complete Or Partial Response In MDS Patients Treated With Azacitidine Outside Clinical Trials

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5203-5203
Author(s):  
Massimo Breccia ◽  
Maria Teresa Voso ◽  
Luca Maurillo ◽  
Pasquale Niscola ◽  
Francesco Autore ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Prognostic Factors ◽  
High Risk ◽  
Who Classification ◽  
Conflicts Of Interest ◽  
Large Series ◽  
Clinical Parameters ◽  
Factors Associated ◽  
Risk Patients ◽  
Cytogenetic Profile

Abstract Azacitidine is able to induce responses and to prolong survival (OS) in intermediate/high risk MDS subgroups or in CMML: in the AZA001 trial, median OS was significantly longer for azacitidine patients compared with the combined conventional care regimen (CCR) group. We retrospectively assessed prognostic factors associated to the achievement of these responses in a large series of MDS patients treated outside clinical trials. Overall, we recruited for this study, 166 primary or secondary MDS and 21 CMML diagnosed and treated with azacitidine in 6 different hematologic units. Patients were recruited consecutively, without any criteria of exclusion. All patients received azacitidine with a schedule of 5+2+2 or of 7 consecutive days every 28 days until progression or unacceptable toxicity. Clinical parameters (age, sex, WHO classification, IPSS) and baseline cytogenetic evaluation were retrospectively collected. Of 166 MDS patients recruited, 103 were males and 63 females; median age was 69.5 years (range 49-89). A median of 8 cycles was performed (range 1-60). According to IPSS stratification there were 29 intermediate-1 risk patients, 118 intermediate-2 patients and 15 high–risk patients (7 patients not determined). According to WHO classification, 37 patients were diagnosed as having RAEB-1, 101 patients as RAEB-2, 28 patients as RCMD. Of 21 CMML patients recruited, 19 were males and 2 females; median age was 67.5 years (range 62-89). According to WHO classification, 14 patients were CMML-2. Overall, 41 patients (22%) achieved a CR/PR according to IWG 2009 criteria. Analysis of factors associated to the achievement of best responses revealed that pre-azacitidine WBC higher than 5 x 109/l (p=0.02) neutrophil count higher than 0.5 x 109/l (p=0.03) and platelet count higher than 150 x 109/l (p=0.01) were significantly associated to CR/PR achievement. We did not reveal significant differences, when compared to patients that did not achieve a response, in terms of sex, age, hemoglobin level at baseline, bone marrow blast count, cytogenetic profile, IPSS stratification. In conclusions, from our results, based on a large series of patients treated outside clinical trials, it seems that, independently from cytogenetic or hematological subtype, only clinical parameters at baseline could influence the achievement of a good response with azacitidine. Disclosures: No relevant conflicts of interest to declare.

Prognostic factors for cancer patients with good performance status considered for inclusion in phase I clinical trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2568-2568
Author(s):  
M. Bonneterre ◽  
N. Penel ◽  
M. Vanseymortier ◽  
E. Dansin ◽  
S. Clisant ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Prognostic Factors ◽  
Serum Albumin ◽  
Phase I ◽  
Cancer Patients ◽  
Cox Model ◽  
Performance Status ◽  
Univariate Analysis ◽  
Rank Test ◽  
Phase I Clinical Trials

2568 Background: For investigators, the selection of patients to be considered for phase I clinical trials is difficult, because of the lack of objective criteria for a rational decision-making process. From October 1997 to October 2002, we retrospectively assessed prognostic factors for cancer patients considered for Phase 1 trials. Methods: 148 consecutive patients who had been screened for inclusion in 6 different phase I trials were included in the present study. 70 out of them actually received the phase I treatment. Univariate (Log-Rank test) and multivariate analysis (Cox proportional hazard ratio model) were performed to determine the prognostic factors related to overall survival (OS) after screening. Results: The study comprised 63 men and 85 women, with a median age of 54 (range 23–79). The most frequent primary cancer sites were: breast (38 cases), head and neck (28 cases), lung (18 cases) and colorectal (17 cases). 91 out of them had a performance status PS = 0. The median OS of the 148 patients was 5.7 months (173 days, range 1–2,421). Univariate analysis identified PS = 1, Body Mass Index < 20, liver and visceral metastasis, serum albumin < 38 g/L, lymphocytes count < 0.7 x 109/L and granulocytes count > 7.5 x 109/L as poor prognostic factors. The Cox model identified serum albumin < 38 g/L (HR 2.51 [1.51–4.18], p=0.0001) and lymphocyte count < 0.7 x 109/L (HR 2.27 [1.13–4.62], p=0.024) as independent prognostic variables for OS. All patients presenting with both prognostic factors died within 90 days. Conclusion: We propose a simple model, easily obtained at the patient bedside, which can discriminate patients who have a life expectancy of over 3 months and thus could be enrolled in phase-I anti-cancer trials. No significant financial relationships to disclose.

Treatment effectiveness in advanced breast cancer patients in Italy: Ten years experience.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11573-e11573
Author(s):  
Sandro Barni ◽  
Ilaria Vallini ◽  
Marta Bonotto ◽  
Antonella Brunello ◽  
Monica Indelli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Prognostic Factors ◽  
Soft Tissue ◽  
Triple Negative ◽  
Demographic Data ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Luminal B ◽  
Oncology Unit

e11573 Background: Several studies suggest that newer therapies can improve survival in MBC, but a different impact on overall survival (OS) is observed according to histology, extension of disease and prognostic factors. This survey was performed for evaluate Italian experience in cancer treatment in the last ten years. Methods: We collected data from 13 Italian Medical Oncology Unit; we registered all consecutive patients (pts) with breast cancer who have developed metastasis between 2000 and 2008. Demographic data, pathological characteristics and treatment were reported. OS was calculated from time of recurrence and stratified according to biological characteristics and to recurrence date. Results: 1542 pts was suitable for analysis; median age 61,7 (range 22-94); MBC at diagnosis 21,8%. Site of disease recurrence: bone 26,2%, visceral 25,4%, bone and visceral 20,7%, soft tissue 11,5%, soft tissue and visceral 8,4%, bone and soft tissue 7,8%. Molecolar classification: luminal A 66,3%, luminal B 14,5%, triple negative 11,5%, HER2+ like 7,7%. Pts received a median of 2 lines of chemotherapy (range 0-10) and 1 line of hormonal therapy (range 0-7); 22,5% received biological drugs. 15,5% of metastatic pts were enrolled in clinical trials. After a median follow up of 7.1 years 84,1% pts died (1297/1542 pts) and median OS was 2,7 years (range 2,6-2,9). We did not observe difference in OS for pts divided into 3 groups according to recurrence date (2000-2002, 2003-2005, 2006-2008). A longer median OS was observed in luminal B (3,8 years) versus luminal A and HER2+ like (2,8 years) and triple negative disease (1,2 years). Conclusions: Our survey describe a large number of MBC pts treated in 13 Italian Oncology Unit. OS analysis did not show significant differences according to recurrence date, but for different prognostic factors. OS data are superimposable to literature ones, showing a good transfer from clinical trials to clinical practice.

Clinical outcomes of intermediate risk metastatic germ cell tumors (IRGCT): Results from a single-institution series.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 380-380
Author(s):  
Daniele Raggi ◽  
Salvatore Lo Vullo ◽  
Patrizia Giannatempo ◽  
Daniele Giardiello ◽  
Nicola Nicolai ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Lung Metastases ◽  
Multivariable Analysis ◽  
Germ Cell Tumors ◽  
Time Frame ◽  
Logrank Test ◽  
First Line Therapy ◽  
Kaplan Meier

380 Background: IRGCT comprises a consistent category of metastatic patients (pts), and information on the recommended management of these pts should be updated. Usually they enter clinical trials for poor prognosis GCT. We aimed to address the heterogeneity of this category and to identify clinical prognostic factors for sub-stratification of pts. Methods: Data on consecutive pts with IRGCT and who received treatment at Fondazione INT Milano in the time-frame 02/1980-03/2014 were collected. Cox regression analyses were done evaluating potential prognostic factors for overall survival (OS, primary endpoint) to first-line therapy. Each factor was evaluated in a multivariable model. An exploratory OS comparison between outlier groups was undertaken with Kaplan Meier curves and logrank test. Results: Data on 181 pts were collected. Median age was 27 yrs (IQR 22-32), 10 pts had a retroperitoneal (RP) primary, 6 had pure seminoma. 72 (39.8%) had lung metastases and 54 (32.3%) bulky (i.e. ≥10cm) RP lymph-nodes (LN). Pts received cisplatin, bleomycin and etoposide (PEB, n=156) or vinblastine (PVB, n=23), 2 other treatments. Median follow up was 173 months (IQR: 87-237). Globally, 5-y PFS and OS were 66.8% (95%CI: 60.1-74.2) and 83.3% (77.8-89.2). However, 5-y OS for pts with AFP 5,000-10,000 IU/ml (N=19) was 61.8% (95%CI: 43.0-88.7) while it was 89.1% (95%CI: 81.2-97.7) for nonseminomas with elevated LDH only (N=57) and similar for elevated HCG only (N=22); overall p<0.001. Multivariable analysis for OS is shown in the table (c-index= 0.63). Distribution of variables over time: bulky RP LN and elevated LDH were more frequent in earlier series (p=0.003 and 0.011). Conclusions: The prognostic heterogeneity of IRGCT category is a matter of fact and should be addressed by clinical trials. Pts with highly elevated AFP have an OS similar to poor prognostic category, while those categorized by elevated HCG or LDH only are close to good risk ones. [Table: see text]

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