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

Abstract

Background: Most 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.

Methods: The 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.

Discussion: 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. 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 registration: EU Clinical Trial Register, EudraCT Number 2014-004552-64 . Registered on 19 January 2016. ClinicalTrials.gov NCT02948309 . Registered on 28 October 2016.

Keywords: Clinical trial; Complementary therapies; Mistletoe; Neoplasms; Palliative care; Pancreatic neoplasms; Quality of life; Randomised controlled trial.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Schedule of enrolment, interventions and assessments 1 Or as close to this date as possible 2 Phone call by study nurse 3 Three subcutaneous injections per week with placebo/ME; dose escalation from 0.01mg to 20mg 4 At screening visit: general condition, heart, lungs, abdomen and icterus (yes/no). At subsequent visits at least abdomen, icterus (yes/no) and general condition 5 Access is documented; referral if medical need for access 6 Recorded by participants in study-specific patient diary: n total parenteral nutrition infusions per week, n visits from palliative home care team per week, consumption of n dietitian-prescribed nutritional supplement drinks per day, injections, dosage, interruptions of study treatment, comments 7 Voluntary for participants at end of study

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