Primary Tumor Resection Before Systemic Therapy in Patients With Colon Cancer and Unresectable Metastases: Combined Results of the SYNCHRONOUS and CCRe-IV Trials.

PURPOSE: Chemotherapy is established as primary treatment in patients with stage IV colorectal cancer and unresectable metastases. Data from nonrandomized clinical trials have fueled persistent uncertainty if primary tumor resection (PTR) before chemotherapy prolongs survival. We investigated the prognostic value of PTR in patients with newly diagnosed stage IV colon cancer who were not amenable to curative treatment. PATIENTS AND METHODS: Patients enrolled in the multicenter, randomized SYNCHRONOUS and CCRe-IV trials were included in the analysis. Patients with colon cancer with synchronous unresectable metastases were randomly assigned at 100 sites in Austria, Germany, and Spain to undergo PTR or up-front chemotherapy (No PTR group). The chemotherapy regimen was left at discretion of the local team. Patients with tumor-related symptoms, inability to tolerate surgery and/or systemic chemotherapy, and history of another cancer were excluded. The primary end point was overall survival (OS), and the analyses were performed with intention-to-treat. RESULTS: A total of 393 patients were randomly assigned to undergo PTR (n = 187) or no PTR (n = 206) between November 2011 and March 2017. Chemotherapy was not administered to 6.4% in the No PTR group and 24.1% in the PTR group. The median follow-up time was 36.7 months (95% CI, 36.6 to 37.3). The median OS was 16.7 months (95% CI, 13.2 to 19.2) in the PTR group and 18.6 months (95% CI, 16.2 to 22.3) in the No PTR group (P = .191). Comparable OS between the study groups was further confirmed on multivariate analysis (hazard ratio, 0.944 [95% CI, 0.738 to 1.209], P = .65) and across all subgroups. Patients with serious adverse events were more common in the No PTR group (10.2% v 18.0%; P = .027). CONCLUSION: Among patients with colon cancer and synchronous unresectable metastases, PTR before systemic chemotherapy was not associated with prolonged OS.

A non-controlled, single arm, open label, phase II study of intravenous and intratumoral administration of ParvOryx in patients with metastatic, inoperable pancreatic cancer: ParvOryx02 protocol.

BACKGROUND: Metastatic pancreatic cancer has a dismal prognosis, with a mean six-month progression-free survival of approximately 50% and a median survival of about 11 months. Despite intensive research, only slight improvements of clinical outcome could be achieved over the last decades. Hence, new and innovative therapeutic strategies are urgently required. ParvOryx is a drug product containing native parvovirus H-1 (H-1PV). Since H-1PV was shown to exert pronounced anti-neoplastic effects in pre-clinical models of pancreatic cancer, the drug appears to be a promising candidate for treatment of this malignancy. METHODS: ParvOryx02 is a non-controlled, single arm, open label, dose-escalating, single center trial. In total seven patients with pancreatic cancer showing at least one hepatic metastasis are to be treated with escalating doses of ParvOryx according to the following schedule: i) 40% of the total dose infused intravenously in equal fractions on four consecutive days, ii) 60% of the total dose injected on a single occasion directly into the hepatic metastasis at varying intervals after intravenous infusions. The main eligibility criteria are: age ≥ 18 years, disease progression despite first-line chemotherapy, and at least one hepatic metastasis. Since it is the second trial within the drug development program, the study primarily explores safety and tolerability after further dose escalation of ParvOryx. The secondary objectives are related to the evaluation of certain aspects of anti-tumor activity and clinical efficacy of the drug. DISCUSSION: This trial strongly contributes to the clinical development program of ParvOryx. The individual hazards for patients included in the current study and the environmental risks are addressed and counteracted adequately. Besides information on safety and tolerability of the treatment after further dose escalation, thorough evaluations of pharmacokinetics and intratumoral spread as well as proof-of-concept (PoC) in pancreatic cancer will be gained in the course of the trial. TRIAL REGISTRATION: ClinicalTrials.gov-ID: NCT02653313 , Registration date: Dec. 4th, 2015.

Stem cell Transplantation for Eradication of Minimal PAncreatic Cancer persisting after surgical Excision (STEM PACE Trial, ISRCTN47877138): study protocol for a phase II study.

BACKGROUND: Pancreatic cancer is the third most common cancer related cause of death. Even in the 15% of patients who are eligible for surgical resection the outlook is dismal with less than 10% of patients surviving after 5 years. Allogeneic hematopoietic (allo-HSCT) stem cell transplantation is an established treatment capable of to providing cure in a variety of hematopoietic malignancies. Best results are achieved when the underlying neoplasm has been turned into a stage of minimal disease by chemotherapy. Allo-HSCT in advanced solid tumors including pancreatic cancer have been of limited success, however studies of allo-HSCT in solid tumors in minimal disease situations have never been performed. The aim of this trial is to provide evidence for the clinical value of allo-HSCT in pancreatic cancer put into a minimal disease status by effective surgical resection and standard adjuvant chemotherapy. METHODS/DESIGN: The STEM PACE trial is a single center, phase II study to evaluate adjuvant allogeneic hematopoietic stem cell transplantation in pancreatic cancer after surgical resection. The study will evaluate as primary endpoint 2 year progression free survival and will generate first time state-of-the-art scientific clinical evidence if allo-HSCT is feasible and if it can provide long term disease control in patients with effectively resected pancreatic cancer. Screened eligible patients after surgical resection and standard adjuvant chemotherapy with HLA matched related stem cell donor can participate. Patients without a matched donor will be used as a historical control. Study patients will undergo standard conditioning for allo-HSCT followed by transplantation of allogeneic unmanipulated peripheral blood stem cells. The follow up of the patients will continue for 2 years. Secondary endpoints will be evaluated on 7 postintervention visits. DISCUSSION: The principal question addressed in this trial is whether allo-HSCT can change the unfavourable natural course of this disease. The underlying hypothesis is that allo-HSCT has the capacity to provide long-term disease control to an extent otherwise not possible in pancreatic cancer, thereby substantially improving survival of affected patients. TRIAL REGISTRATION: This trial has been registered: ISRCTN47877138.

Design of a prospective clinical study on the agreement between the Continuous GlucoseMonitor, a novel device for CONTinuous ASSessment of blood GLUcose levels, and the RAPIDLab® 1265 blood gas analyser: The CONTASSGLU study.

BACKGROUND: Although a device is needed to continuously measure blood glucose levels within an intensive care setting, and several large-scale prospective studies have shown that patients might benefit from intensive insulin, potassium, or glucose therapy during intensive care, no devices are currently available to continuously assess blood glucose levels in critically ill patients. We conceived the study described here to evaluate the clinical use of the Continuous Glucose Monitor (CGM) performed via a central vein, and to determine the impact of phenomena, such as drift and shift, on the agreement between the CGM and a RAPIDLab® 1265 blood gas analyser (BGA). METHODS/DESIGN: In the CONTinuous ASSessment of blood GLUcose (CONTASSGLU) study, up to 130 patients under intensive care will be fitted with the CGM, an ex vivo device that continuously measures blood glucose and lactate levels. Readings from the device taken 8 h after initial placement and calibration will be compared with values measured by a BGA. For this study, we chose the BGA as it is an established standard point-of-care device, instead of the devices used in certified central laboratories. Nevertheless, we will also independently compare the results from the point-of-care BGA with those determined by a central laboratory-based device. Blood samples will be collected from each patient from the same site in which the CGM will measure blood glucose. Consequently, each participant will serve as their own control, and no randomisation is necessary. The 95% limits of agreement and the corresponding confidence intervals will be calculated and compared with a prespecified clinically acceptable relative difference of 20%. DISCUSSION: Several attempts have been made to develop a device to continuously measure blood glucose levels within an intensive care setting or to use the devices that were originally designed for diabetes management, as several of these devices are already available. However, none of these devices were successful in intensive care settings. CONTASSGLU may well bridge this gap by confirming the ability of the CGM to continuously measure blood glucose levels in intensive care settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT01580176.