Mistletoe Therapy in Primary and Recurrent Inoperable Pancreatic Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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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

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Mistletoe extract (Iscador Qu)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mistletoe extract (Iscador Qu)<br>Fermented aqueous extract of Viscum album ssp album (L.) (mistletoe) = Iscador Qu, subcutaneous use 3 injections/week; dose escalation from 0,01mg - 20mg | Drug: Mistletoe extract (Iscador Qu)<br>* 1ml subcutaneous injection 3 times/week, dose escalation 0,01mg - 20mg<br>* Other names: Fermented aqueous extract of Viscum album ssp album (L.);|
| Placebo Comparator: Placebo<br>isotonic saline solution, subcutaneous use 3 injections/week | Drug: Placebo<br>* 1ml subcutaneous injection 3 times/week<br>* Other names: Isotonic saline solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | OS defined as time from randomization to death for any reason | End of study (estimated 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life questionnaire EORTC QLQ-C30 | Evaluation according to EORTC QLQ-C30 Scoring Manual | At 7 visits during study (9 months) | 
| Quality of Life questionnaire EORTC PAN -26 | Evaluation according to EORTC PAN-26 Scoring Manual | At 7 visits during study (9 months) | 
| Weight in kilograms, height in meters, BMI in kg/m^2 | Body weight, Body Mass Index | At 7 visits during study (9 months) | 
| 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) | 
| Number of visits of homecare team per week | Costs for supportive care | At 7 visits during study (9 months) | 
| Use of oral nutrition support per week (number used per day) | Costs for supportive care | At 7 visits during study (9 months) | 
| Use of symptom relieving medication in mg/day (painkillers, antiemetic and anxiolitic medication) | Costs for supportive care | At 7 visits during study (9 months) | 
| Chemotherapy use (number of cycles first line, second line, ..) and dose reduction in% | Costs for supportive care | At 7 visits during study (9 months) | 
| Number of parenteral nutrition infusions per week | Costs for supportive care | At 7 visits during study (9 months) | 
| Days of unplanned inpatient care | Costs for inpatient care | At 7 visits during study (9 months) | 
| Incidence of treatment-emergent adverse events (AE) | Safety | Through study completion (9 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary diagnosis, Relapse