Mistletoe Therapy in Primary and Recurrent Inoperable Pancreatic Cancer

Pancreatic Cancer Clinical Trial

— MISTRAL  

Official title:

Mistletoe Therapy in Primary & Recurrent Inoperable Pancreatic Cancer. A Phase III Prospective Randomized Double Blinded Multicenter Parallel Group Placebo Controlled Clinical Trial on Overall Survival and Quality of Life

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02948309
• Other study ID #: 131016
• Secondary ID: 2014-004552-64
• Status: Completed
• Phase: Phase 3
• Start date: June 2016
• Est. completion date: September 2022

Study information

• Verified date: January 2023
• Source: Karolinska University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this study a mistletoe preparation (Iscador Qu) is added to standard therapy in inoperable pancreatic cancer in order to evaluate effect on overall survival and health-related quality of life. Half of participants will take subcutaneous injections with mistletoe in addition to standard therapy (palliative chemotherapy or best supportive care); the other half will receive a placebo and standard therapy.

Description:

Extracts from European mistletoe (Viscum album L.) have been used as complementary cancer therapy since the 1920s. To date over 160 clinical studies on mistletoe in cancer therapy have been conducted with varying quality; the therapy is still controversial.

Best evidence is found for increase of health-related quality of life (HRQoL) and reduction of side effects of conventional therapies (chemotherapy, radiation) in breast cancer patients. Mistletoe treatment is described as safe and well tolerated. There are some clinical studies supporting the use of mistletoe extract in the management of late stage cancer.

Statistically significant effects on overall survival (OS) and HRQoL in pancreatic cancer patients have recently been shown in a randomized open label trial in Serbia investigating the addition of mistletoe extract to best supportive care. The results are questioned because patients knew what kind of treatment they received.

Mistletoe extracts are usually administered subcutaneously. They contain a multitude of substances with immune modulatory and cytotoxic or - in animal studies - antitumorigenic, anti-metastatic and antiangiogenic effects.

This trial investigates whether there is a beneficial effect of mistletoe extracts on OS and HRQoL in pancreatic cancer patients receiving standard treatment (palliative chemotherapy or best supportive care).

Inclusion has started at 4 study centers (2 more centers are waiting for participation). And participants are randomized 1:1 to mistletoe treatment (Iscador Qu®) given in increasing dosage from 0,01mg to 20 mg or placebo injections subcutaneously 3 times /week. Stratification will be performed for received oncological treatment (palliative chemotherapy or best supportive care). At 7 visits in 9 months, participants fill in the validated EORTC QLQ-C30 (QLO=quality of life questionnaire) and PAN-26 (PAN=pancreas) quality of life questionnaires. Body weight, use of cancer-related medicines, substitution of nutrition, adverse events need of supportive care and inpatient care are measured. To be able to assess more dimensions of quality of life than possible with questionnaires, a qualitative sub-study with interviews on about 30 participants in this trial is performed in month 3. A 2nd substudy has been added november 2016 to elucidate the systemic effects of mistletoe therapy and to explore potential prognostic and predictive biomarkers (anticipated n=100).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 290
• Est. completion date: September 2022
• Est. primary completion date: September 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Signed written informed consent

• Age = 18 years

• Inoperable locally advanced or metastatic pancreatic cancer or relapse of pancreatic cancer.

• Primary diagnosis: if histology is not clinically achievable diagnosis is to be confirmed according to local practice sufficient for diagnosis and choice of therapy (such as CA19-9 (=cancer antigen 19-9) and CT).

• Relapse: histology (not required) or diagnosis according to local practice such as clinical signs and/or imaging and/or CA19-9.

• ECOG ( Eastern Cooperative Oncology Group) performance status 0-2 (see table in section 12.14 )

• Adequate negative pregnancy test and adequate contraception (where appropriate)

Exclusion Criteria:

Life expectancy less than 4 weeks

• Pregnancy or breastfeeding

• Neuroendocrine tumors of the pancreas (NET)

• Current use of interferon, G-CSF (granulocyte colony-stimulating factor) and thymus preparations

• Symptomatic brain edema due to brain metastases

• Known hypersensitivity to mistletoe-containing products

• Current use of mistletoe extract preparations in any form

• Chronic granulomatous disease or active autoimmune disease or autoimmune disease with immunosuppressive treatment

• Medical, psychiatric, cognitive or other conditions that may compromise the patient´s ability to understand the patient information, give informed consent, comply with the study protocol or complete the study (e.g. needle phobia).

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• Mistletoe extract (Iscador Qu)
1ml subcutaneous injection 3 times/week, dose escalation 0,01mg - 20mg
• Placebo
1ml subcutaneous injection 3 times/week

Locations

Country	Name	City	State
Sweden	Kathrin Wode	Stockholm

Sponsors (11)

Lead Sponsor	Collaborator
Karolinska University Hospital	Cancerforskningsfonden i Norrland, Dagmar Ferbs Minnesfond, Ekhagastiftelsen, Immunpathologisches Labor, University Tübingen, Karolinska Institutet, Regional Cancer Centre Stockholm Gotland, Signe & Ane Gyllenbergs Stiftelse, Stiftelsen Konung Gustaf V:s Jubileumsfond för cancerforskning, The Sjöberg Foundation, University of Witten/Herdecke

Country where clinical trial is conducted

Sweden, 

References & Publications (4)

Horneber MA, Bueschel G, Huber R, Linde K, Rostock M. Mistletoe therapy in oncology. Cochrane Database Syst Rev. 2008 Apr 16;2008(2):CD003297. doi: 10.1002/14651858.CD003297.pub2. — View Citation

Kienle GS, Glockmann A, Schink M, Kiene H. Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research. J Exp Clin Cancer Res. 2009 Jun 11;28(1):79. doi: 10.1186/1756-9966-28-79. — View Citation

Troger W, Galun D, Reif M, Schumann A, Stankovic N, Milicevic M. Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a randomized controlled trial. Dtsch Arztebl Int. 2014 Jul 21;111(29-30):493-502, 33 p following 502. doi: 10.3238/arztebl.2014.0493. — View Citation

Troger W, Galun D, Reif M, Schumann A, Stankovic N, Milicevic M. Viscum album [L.] extract therapy in patients with locally advanced or metastatic pancreatic cancer: a randomised clinical trial on overall survival. Eur J Cancer. 2013 Dec;49(18):3788-97. doi: 10.1016/j.ejca.2013.06.043. Epub 2013 Jul 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS)	OS defined as time from randomization to death for any reason	End of study (estimated 3 years)
Secondary	Quality of Life questionnaire EORTC QLQ-C30	Evaluation according to EORTC QLQ-C30 Scoring Manual	At 7 visits during study (9 months)
Secondary	Quality of Life questionnaire EORTC PAN -26	Evaluation according to EORTC PAN-26 Scoring Manual	At 7 visits during study (9 months)
Secondary	Weight in kilograms, height in meters, BMI in kg/m^2	Body weight, Body Mass Index	At 7 visits during study (9 months)
Secondary	Corticosteroid use in milligrams betamethasone per day and indication (appetite, chemotherapy, nausea, pain, general wellbeing, other: specified)	Corticosteroid use and indication	At 7 visits during study (9 months)
Secondary	Number of visits of homecare team per week	Costs for supportive care	At 7 visits during study (9 months)
Secondary	Use of oral nutrition support per week (number used per day)	Costs for supportive care	At 7 visits during study (9 months)
Secondary	Use of symptom relieving medication in mg/day (painkillers, antiemetic and anxiolitic medication)	Costs for supportive care	At 7 visits during study (9 months)
Secondary	Chemotherapy use (number of cycles first line, second line, ..) and dose reduction in%	Costs for supportive care	At 7 visits during study (9 months)
Secondary	Number of parenteral nutrition infusions per week	Costs for supportive care	At 7 visits during study (9 months)
Secondary	Days of unplanned inpatient care	Costs for inpatient care	At 7 visits during study (9 months)
Secondary	Incidence of treatment-emergent adverse events (AE)	Safety	Through study completion (9 months)