scholarly journals Protocol of a prospective, monocentric phase I/II feasibility study investigating the safety of multimodality treatment with a combination of intraoperative chemotherapy and surgical resection in locally confined or borderline resectable pancreatic cancer: the combiCaRe study

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e028696
Author(s):  
Susanne Roth ◽  
Christoph Springfeld ◽  
Markus K Diener ◽  
Christine Tjaden ◽  
Phillip Knebel ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Surgical Resection ◽  
Feasibility Study ◽  
Standard Treatment ◽  
Perioperative Chemotherapy ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Reference Number ◽  
Intraoperative Chemotherapy

IntroductionPancreatic cancer is a devastating disease with an exceptionally poor prognosis. Complete resection of the primary tumour followed by adjuvant chemotherapy is the current standard treatment for patients with resectable disease and the only curative treatment option. However, long-term survival remains rare. Tumour cell dissemination due to manipulation during surgery may increase the rate of future metastases and local recurrence, and perioperative chemotherapy might diminish local, distant and circulating minimal residual disease. Yet, safety and feasibility of systemic chemotherapeutic treatments during pancreatic cancer resection have to be evaluated in a first instance.Methods and analysisThis is a prospective, single-centre phase I/II feasibility study to investigate the safety and tolerability of a combination of intraoperative chemotherapy and surgical resection in pancreatic cancer. Forty patients with locally confined or borderline resectable pancreatic cancer, meeting all proposed criteria will be included. Participants will receive 400 mg/m2 calcium folinate over 2 hours and 2000 mg/m2 5-fluorouracil over 48 hours, started on the day before pancreatic surgery and thus continuing during surgery. Participants will be followed until 60 days after surgery. The primary endpoint is the 30-day overall complication rate according to the Clavien-Dindo classification. Secondary endpoints comprise toxicity and treatment associated complications. Patients receiving perioperative chemotherapy will be compared with a propensity score matched contemporary control group of 70 patients with pancreatic cancer receiving the standard treatment. This trial also contains an ancillary translational study to analyse disseminated tumour cells and effects of pharmacological interventions in pancreatic cancer.Ethics and disseminationCombiCaRe has been approved by the German Federal Institute for Drugs and Medical Devices (reference number 4042787) and the Medical Ethics Committee of Heidelberg University (reference number AFmo-269/2018). The results of this trial will be presented at national and international conferences and published in peer-reviewed journals.Trial registration numberGerman Clinical Trials Register (DRKS00015766).

Clinical outcomes in borderline resectable pancreatic cancer: A cohort study.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 494-494
Author(s):  
Davendra Sohal ◽  
Mohammad Altujjar ◽  
Katherine Tullio ◽  
Mohamed Abazeed ◽  
Robert James Pelley ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cohort Study ◽  
Surgical Resection ◽  
Cleveland Clinic ◽  
Pancreatic Head ◽  
Vascular Involvement ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Cross Sectional ◽  
Borderline Resectable Pancreatic Cancer

494 Background: The management of borderline resectable pancreatic cancer (BRPC) remains unsettled and the predictors of outcome are uncertain. We evaluated the role of neoadjuvant therapy (nRx) and outcomes in patients with BRPC. Methods: We conducted a retrospective cohort study of consecutive patients with BRPC who received nRx and were followed at the Cleveland Clinic. A histopathologic diagnosis of pancreatic carcinoma was required. Tumor anatomy was assessed by contrast-enhanced cross-sectional imaging (CT or MRI), and BRPC was defined as a tumor-vessel wall interface involving one or more of: celiac artery, superior mesenteric artery, common hepatic artery, main portal vein, superior mesenteric vein; making margin-negative resection unlikely. Baseline laparoscopy was performed to rule out occult metastatic disease. Chemotherapy (CT), radiation (RT), surgery details, and pathologic and survival outcomes were evaluated. Hazard ratios (HR) with 95% confidence intervals (CI) and 2-sided p-values are presented. Results: The study population comprised 79 patients from 2009 to 2014. Median age was 64 years; 52% were male; 85% were Caucasian. Pancreatic head/neck were the primary site in 81%; body/tail in 19%. Vascular involvement included arterial in 32 (41%), and venous in 65 (82%) patients. nRx included RT in all patients; 77 (97%) received CT; gemcitabine (n = 50, 63%) was the most common agent. After CT/RT, 36 (46%) patients had unresectable/inoperable disease: 29 (37%) for anatomic reasons, 4 (5%) for physiologic reasons, and 3 (4%) for both. Surgical resection was performed in 43 (54%) patients; 38 (88%) had negative margins; 30 (70%) had negative nodes; 32 (74%) received adjuvant CT. There were no statistically significant predictors of resection. After median follow-up of 27 mths, there have been 45 deaths (57%); median overall survival (mOS) is 23.5 mths (95% CI: 16-28 mths). Only cancer resection was associated with survival (mOS, resected: not reached; mOS, not resected: 12.8 mths; HR: 0.30, 95% CI: 0.16-0.56, p = 0.0002). Conclusions: Surgical resection, if feasible, of BRPC is associated with improved OS. Strategies to improve the odds of resection should be evaluated in prospective studies.

scholarly journals Phase I Study of Nab–Paclitaxel plus Gemcitabine as Neoadjuvant Therapy for Borderline Resectable Pancreatic Cancer

2017 ◽  
Vol 37 (2) ◽  
pp. 853-858 ◽  
Author(s):  
KEN-ICHI OKADA ◽  
SEIKO HIRONO ◽  
MANABU KAWAI ◽  
MOTOKI MIYAZAWA ◽  
ATSUSHI SHIMIZU ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Neoadjuvant Therapy ◽  
Phase I Study ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer

Prospective phase I study of nab-paclitaxel plus gemcitabine with concurrent MR-guided IMRT in patients with locally advanced or borderline resectable pancreatic cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS480-TPS480
Author(s):  
Jeffrey R. Olsen ◽  
Parag J. Parikh ◽  
Todd A. DeWees ◽  
Lindsey Olsen ◽  
William G. Hawkins ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Dose Level ◽  
Phase I Study ◽  
Locally Advanced ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Cine Mr ◽  
Patient Reported

TPS480 Background: Radiotherapy (RT) for locally advanced and borderline resectable pancreatic cancer (LABPC) is controversial as potential local control benefits are often obscured by high rates of distant progression. However, local failure remains a significant cause of morbidity among patients without distant progression after initial chemotherapy, although toxicity concerns may limit delivery of optimal systemic therapy concurrent with RT. Given known systemic efficacy and radiosensitization effects of nab-paclitaxel (A) with gemcitabine (G), we initiated a phase I study of nab-paclitaxel with gemcitabine (AG) and concurrent intensity modulated radiation therapy with magnetic resonance guidance (MR-IMRT) for LABPC. Methods: A planned 24 patients with LABPC will be enrolled to a phase I dose escalation trial using the Time-to-Event Continual Reassessment Method (TITE-CRM) design. Following one lead-in cycle of GA, MR-IMRT is administered daily with concurrent weekly GA for a total of 25 fractions in 5 weeks. The initial dose levels for RT and AG, respectively, are: 40 Gy MR-IMRT, 75 mg/m2 A and 600mg/m2 G. The maximum possible dose level is 60 Gy MR-IMRT, 100mg/m2 A and 1000mg/m2 G. To reduce toxicity risk, MR-IMRT volumes include the primary tumor only, with cine-MR used for intra-fraction tumor tracking in place of fiducial markers. The primary endpoint is determination of the maximum tolerated dose level, with secondary endpoints including rate of conversion to resectable disease, progression- free survival, overall survival, and patient reported quality of life. Clinical trial information: NCT02283372.

scholarly journals SPARC: A phase-I trial of pre-operative margin-intensified stereotactic radiotherapy for pancreatic cancer at high risk of positive resection margins.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS536-TPS536
Author(s):  
Daniel Holyoake ◽  
Maxwell Robinson ◽  
Victoria Y Strauss ◽  
Gavin Reilly ◽  
David McIntosh ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Dose Escalation ◽  
Stereotactic Radiotherapy ◽  
Maximum Tolerated Dose ◽  
Radiotherapy Planning ◽  
Resection Margins ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer

TPS536 Background: Standard therapy for resectable and borderline resectable pancreatic cancer in the UK is surgery with adjuvant chemotherapy, but clear resection margins rates are unsatisfactory. Conventional neoadjuvant radiotherapy has limited efficacy, but stereotactic radiotherapy (SBRT) achieves accuracy and precision to enable dose escalation and margin-intensification, with the goal of achieving clear resection margins. This prospective multi-centre study aims to establish the maximum tolerated dose of margin-intensified pre-operative SBRT, for subsequent definitive comparison with other neoadjuvant treatment options. Methods: SPARC is a phase-I dose-escalation study (NCT02308722). A ‘rolling-six’ design is utilised to minimise delays and facilitate ongoing recruitment during dose escalation. Eligibility comprises histologically or cytologically proven borderline-resectable pancreatic cancer, or operable tumour in contact with vessels increasing the risk of positive margin. Up to 24 patients will be recruited from up to 5 treating centres. Radiotherapy is delivered in 5 daily fractions, with surgery planned to take place 5–6 weeks later. The margin-intense radiotherapy concept utilises a systematic method to define the target volume for a simultaneous integrated boost in the region of tumour-vessel infiltration. Up to 4 radiotherapy dose levels will be investigated, and the maximum tolerated dose is the highest dose at which no more than 1 of 6 patients or 0 of 3 patients experience a dose limiting toxicity. Secondary endpoints include resection rate, resection margin status, response rate, overall survival, and progression free survival at 12 and 24 months. Translational work will involve exploratory analyses of the cytological and humoral immunological responses to SBRT in pancreatic cancer. Radiotherapy quality assurance of target definition and radiotherapy planning is enforced with pre-trial test cases and on-trial review. Recruitment began in April 2015 and eleven patients have been treated to date. Cohort 1 was completed without DLT and recruitment to cohort 2 began in September 2016. Clinical trial information: NCT02308722.

Treatment strategy for borderline resectable pancreatic cancer with artery involvement.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 373-373
Author(s):  
Seiko Hirono ◽  
Manabu Kawai ◽  
Ken-Ichi Okada ◽  
Motoki Miyazawa ◽  
Atsushi Shimizu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Surgical Resection ◽  
Neoadjuvant Treatment ◽  
Positive Lymph Node ◽  
University Hospital ◽  
High Morbidity ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer

373 Background: It has been still controversial to perform surgical resection with borderline resectable pancreatic cancer with artery involvement (BR-A), because an aggressive surgery leads to high morbidity and mortality with low R0 rate for the BR-A patients. In this study, we evaluated whether or not neoadjuvant therapy followed by surgical resection improves survival benefits for BR-A patients. Methods: There were 138 patients with BR-A among 330 pancreatic cancer patients underwent surgical resection at Wakayama Medical University Hospital. We compared clinicopathological factors between 38 BR-A patients with neoadjuvant therapy followed by surgical resection and 100 BR-A patients with upfront surgery to evaluate the clinical impacts of neoadjuvant therapy. Results: The overall survival (OS) of BR-A patients was significantly shorter than that of the patients with borderline resectbale pancreatic cancer with portal vein/ superior mesenteric vein (PV/SMV) involvement (n=76) and resectable pancreatic cancer (n=105) who underwent surgical resection (median OS: 13.6 vs. 20.6 months, P<0.001). The OS of BR-A patient with neoadjuvant therapy followed by surgical resection was significantly longer than those with upfront surgery (median OS: 20.2 vs. 12.9 months, P=0.047). Multivariate analysis showed that older age (P=0.027), pathological PV/SMV invasion (P=0.031), moderated or poor differentiated tumor (P=0.008), positive lymph node ratio ³a0.1 (P=0.018), and no postoperative adjuvant chemotherapy (P<0.001) were independent poor prognostic factors for BR-A patients. Conclusions: Neoadjuvant treatment might bring the clinical benefits for BR-A patients, and it is important to develop the appropriate regimen of neoadjuvant therapy and postoperative adjuvant therapy for longer survival in BR-A patients. Clinical trial information: 000003795.

scholarly journals Neoadjuvant therapy may lead to successful surgical resection and improved survival in patients with borderline resectable pancreatic cancer

HPB ◽  
2010 ◽  
Vol 12 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Rebecca J. McClaine ◽  
Andrew M. Lowy ◽  
Jeffrey J. Sussman ◽  
Nathan Schmulewitz ◽  
David L. Grisell ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Surgical Resection ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer
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