Improving phase II oncology trials using best observed RECIST response as an endpoint by modelling continuous tumour measurements.

In many phase II trials in solid tumours, patients are assessed using endpoints based on the Response Evaluation Criteria in Solid Tumours (RECIST) scale. Often, analyses are based on the response rate. This is the proportion of patients who have an observed tumour shrinkage above a predefined level and no new tumour lesions. The augmented binary method has been proposed to improve the precision of the estimator of the response rate. The method involves modelling the tumour shrinkage to avoid dichotomising it. However, in many trials the best observed response is used as the primary outcome. In such trials, patients are followed until progression, and their best observed RECIST outcome is used as the primary endpoint. In this paper, we propose a method that extends the augmented binary method so that it can be used when the outcome is best observed response. We show through simulated data and data from a real phase II cancer trial that this method improves power in both single-arm and randomised trials. The average gain in power compared to the traditional analysis is equivalent to approximately a 35% increase in sample size. A modified version of the method is proposed to reduce the computational effort required. We show this modified method maintains much of the efficiency advantages

An unusual presentation of multiple cavitated lung metastases from colon carcinoma

<p>Abstract</p> <p>Background</p> <p>Consolidation with or without ground-glass opacity is the typical radiologic finding of lung metastases of adenocarcinoma from the gastrointestinal tract. Lung excavated metastases from gastrointestinal carcinoma are very rare.</p> <p>Case presentation</p> <p>The authors describe an unusual presentation of multiple cavitated lung metastases from colon adenocarcinoma and discuss the outcome of a patient. The absence both of symptoms and other disease localizations, the investigations related to different diagnostic hypotheses and the empirical treatments caused a delay in correct diagnosis. Only a transparietal biopsy revealed the neoplastic origin of nodules.</p> <p>Conclusions</p> <p>This report demonstrates that although lung excavated metastases are described in literature, initial failure to reach a diagnosis is common. We would like to alert clinicians and radiologists to the possibility of unusual atypical features of pulmonary metastases from colon adenocarcinoma.</p

Golimumab, a human antibody to tumour necrosis factor α given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study

Objective: The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy. Methods: Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n = 133), golimumab 100 mg injections plus placebo capsules (group 2, n = 133), golimumab 50 mg injections plus methotrexate capsules (group 3, n = 89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n = 89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24. Results: The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0

Use of Non-concurrent Common Control in Master Protocols in Oncology Trials: Report of an American Statistical Association Biopharmaceutical Section Open Forum Discussion

This article summarizes the discussions from the American Statistical Association (ASA) Biopharmaceutical (BIOP) Section Open Forum that took place on December 10, 2020 and was organized by the ASA BIOP Statistical Methods in Oncology Scientific Working Group, in coordination with the US FDA Oncology Center of Excellence. Diverse stakeholders including experts from international regulatory agencies, academicians, and representatives of the pharmaceutical industry engaged in a discussion on the use of non-concurrent control in Master Protocols for oncology trials. While the use of non-concurrent control with the concurrent control may increase the power of detecting the therapeutic difference between a treatment and the control, the panelists had diverse opinion on the statistical approaches for modeling non-concurrent and concurrent controls. Some were more concerned about the temporality of the non-concurrent control and bias introduced by different confounders related to time, e.g., changes in standard of care, changes in patient population, changes in recruiting strategies, changes in assessment of endpoints. Nevertheless, in some situations such as when the recruitment is extremely challenging for a rare disease, the panelists concluded that the use of a non-concurrent control can be justified

Raltitrexed (Tomudex) administration in patients with relapsed metastatic colorectal cancer after weekly irinotecan/5-Fluorouracil/Leucovorin chemotherapy

PURPOSE: The present study aimed at evaluating the efficacy of Raltitrexed, a specific thymidilate synthase inhibitor, in patients with advanced colorectal cancer (ACC) in relapse (>8 weeks) after a prior response or disease stabilization to first-line chemotherapy combination with lrinotecan+5-Fluorouracil (5-FU)+Leucovorin (LV). METHODS: Twenty-five patients with metastatic ACC entered; 17 males/8 females, median age 61 (range: 47–70), median Karnovsky PS: 80 (70–90), and sites of metastases; liver: 21, lung: 4, lymph nodes: 7, peritoneal: 5 and a life expectancy of at least 3 months, were entered in the present pilot study. All patients had progressed after prior chemotherapy with lrinotecan+5-FU+LV. Raltitrexed was administered at a dose of 3 mg/m(2) i.v. every 21 days. RESULTS: Three patients (12%) achieved a partial response (PR), 8 (32%) had stable disease (SD), and the remaining 14 (56%) developed progressive disease (PD). Median time-to-progression (TTP) was 5.5 months (range, 2–8.5), and median overall survival (OS) 8 months (range, 4.0–12.5). Toxicity was generally mild; it consisted mainly of myelosuppression; neutropenia grade 1–2: 52%-grade 3: 28%, and anemia grade 1–2 only: 36%. Mild mucositis grade 1–2 occured in 13.5% of patients and was the principal non-hematologic toxicity. CONCLUSION: Response to treatment with Raltitrexed is limited in patients with ACC failing after an initial response or non-progression to the weekly lrinotecan+5-FU+LV combination. However, it appears that a limited number of patients with PR/SD may derive clinical benefit, but final proof would require a randomized study

Phase III trial of postoperative cisplatin, interferon alpha-2b, and 5-FU combined with external radiation treatment versus 5-FU alone for patients with resected pancreatic adenocarcinoma – CapRI: study protocol [ISRCTN62866759]

After surgical intervention with curative intention in specialised centres the five-year survival of patients with carcinoma of the exocrine pancreas is only 15%. The ESPAC-1 trial showed an increased five-year survival of 21% achieved with adjuvant chemotherapy. Investigators from the Virginia Mason Clinic have reported a 5-year survival rate of 55% in a phase II trial evaluating adjuvant chemotherapy, immunotherapy and external-beam radiation. DESIGN: The CapRI study is an open, controlled, prospective, randomised multi-centre phase III trial. Patients in study arm A will be treated as outpatients with 5-Fluorouracil; Cisplatin and 3 million units Interferon alpha-2b for 5 1/2 weeks combined with external beam radiation. After chemo-radiation the patients receive continuous 5-FU infusions for two more cycles. Patients in study arm B will be treated as outpatients with intravenous bolus injections of folinic acid, followed by intravenous bolus injections of 5-FU given on 5 consecutive days every 28 days for 6 cycles. A total of 110 patients with specimen-proven R0 or R1 resected pancreatic adenocarcinoma will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patients' enrolment. DISCUSSION: The aim of this study is to evaluate the overall survival period attained by chemo-radiotherapy including interferon alpha 2b administration with adjuvant chemotherapy. The influence of interferon alpha on the effectiveness of the patients' chemoradiation regimen, the toxicity, the disease-free interval and the quality of life are analysed. Different factors are tested in terms of their potential role as predictive markers