Efficacy of mistletoe extract as a complement to standard treatment in advanced pancreatic cancer: study protocol for a multicentre, parallel group, double-blind, randomised, placebo-controlled clinical trial (MISTRAL)

Kathrin Wode,Britt-Marie Bernhardson,Berit Sunde,Johanna Hök Nordberg,Per Fransson,Gunver S Kienle,Lena Sharp,Roger Henriksson,Nils O Elander

doi:10.1186/s13063-020-04581-y

Abstract

BackgroundMost pancreatic cancer patients present with advanced stage at diagnosis with extremely short expected survival and few treatment options. A multimodal palliative approach is necessary for symptom relief and optimisation of health-related quality of life. In a recent open-label trial of mistletoe extract for advanced pancreatic cancer patients not eligible for chemotherapy, promising results on improved overall survival and better health-related quality of life were reported.The objective of the present study is to assess the value of mistletoe extract as a complement to standard treatment (palliative chemotherapy or best supportive care) in advanced pancreatic cancer patients with regard to overall survival and health-related quality of life.MethodsThe trial is prospective, randomised, double-blind, multicentre, parallel group and placebo-controlled. In total, 290 participants are randomly assigned to placebo or mistletoe extract given subcutaneously in increasing dosage from 0.01 to 20 mg three times per week for 9 months. Stratification is performed for site and palliative chemotherapy. Main inclusion criteria are advanced pancreatic cancer and Eastern Cooperative Oncology Group performance status 0 to 2; main exclusion criteria are life expectancy less than 4 weeks and neuroendocrine tumour of the pancreas. Two ancillary studies on sub-sets of participants are nested in the trial: a biomarker study collecting blood samples and a cross-sectional qualitative study with semi-structured face-to-face interviews.DiscussionTo our knowledge, this is the first placebo-controlled randomised trial assessing the impact of mistletoe extract as a complement to standard treatment on overall survival and health-related quality of life in patients with advanced pancreatic cancer. The presented trial with its two nested ancillary studies exploring biomarkers and patient experiences is expected to give new insights into the treatment of advanced pancreatic cancer.Trial registrationEU Clinical Trial Register, EudraCT Number 2014-004552-64. Registered on 19 January 2016.ClinicalTrials.gov NCT02948309. Registered on 28 October 2016.

Highlights

Background and rationale {6a} Pancreatic cancer is currently the fourth most common cause of cancer-related deaths worldwide and is estimated to climb to second place by 2030 [1]
Wode et al Trials (2020) 21:783 (Continued from previous page). To our knowledge, this is the first placebo-controlled randomised trial assessing the impact of mistletoe extract as a complement to standard treatment on overall survival and health-related quality of life in patients with advanced pancreatic cancer
Considering the pessimistic prognosis with short expected survival and considerable symptom burden for patients with advanced pancreatic cancer, there is an urgent need for more effective treatment options to prolong overall survival (OS) and improve health-related quality of life (HRQoL)

Summary

Introduction

Background and rationale {6a} Pancreatic cancer is currently the fourth most common cause of cancer-related deaths worldwide and is estimated to climb to second place by 2030 [1]. The combined impact of severe symptoms and comorbidities associated with the disease most often lead to a rapid deterioration of performance status and health-related quality of life (HRQoL). 80–85% of the newly diagnosed patients present with locally advanced and/or metastatic disease which preclude this type of curative intent strategy. Most pancreatic cancer patients present with advanced stage at diagnosis with extremely short expected survival and few treatment options. In a recent open-label trial of mistletoe extract for advanced pancreatic cancer patients not eligible for chemotherapy, promising results on improved overall survival and better health-related quality of life were reported. The objective of the present study is to assess the value of mistletoe extract as a complement to standard treatment (palliative chemotherapy or best supportive care) in advanced pancreatic cancer patients with regard to overall survival and healthrelated quality of life

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Conclusion