Safety and Modulation of Adaptive Immunity by Iscador® Qu Viscum Album Extract in Patients With Advanced, Recurrent or Metastatic Cancers Treated With Immune Checkpoint Inhibitors (ISCA-CHECK)

Safety and Modulation of Adaptive Immunity by Iscador® Qu Viscum Album Extract in Patients With Advanced, Recurrent or Metastatic Cancers Treated With Immune Checkpoint Inhibitors - a Randomized Trial

The main objective of this study is to test if adding the mistletoe extract Iscador® Qu to regular cancer treatment with immune checkpoint inhibitors affects:

• The immune system's ability to fight cancer
• Safety of the treatment
• How well the treatment performs against cancer
• How the patient feels during treatment

Researchers will compare patients treated with immune checkpoint inhibitors plus Iscador® Qu with patients treated with imune checkpoint inhibitors only.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: Immune checkpoint inhibitors plus Iscador® Qu.; Drug: Immune Checkpoint Inhibitors

Detailed Description

The impact of mistletoe preparations - that are claimed to have immunostimulatory properties - on cancer treatment with immune checkpoint inhibitors remains unclear. To address this knowledge gap, the current study aims to investigate the modulation of adaptive immunity through the combination of Iscador (a specific mistletoe preparation) and immune checkpoint inhibitors. Additionally, researchers will evaluate the safety profile of this combination therapy in patients with locally advanced non-operable or metastatic cancers except for skin cancers. By examining the modulation of adaptive immunity and safety of this treatment approach, researchers aim to provide valuable insights for clinicians and patients in the context of advanced cancer care.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Mascha Binder, Prof. Dr.; Phone Number: +41 61 265 50 75; Email: mascha.binder@unibas.ch
• Study Contact Backup: Name: Benjamin Kasenda, PD Dr. Dr.; Phone Number: +41 61 265 50 75; Email: Benjamin.Kasenda@usb.ch

Study Locations

• Switzerland
  • Baden, Switzerland, 5404
    • Recruiting
    • Kantosspital Baden AG
    • Contact: Sacha Rothschild, Prof. Dr. Dr.; Phone Number: +41 56 486 27 62; Email: Sacha.Rothschild@ksb.ch
    • Principal Investigator: Sacha Rothschild, Prof. Dr. Dr.
  • Basel, Switzerland, 4031
    • Recruiting
    • Universitatsspital Basel
    • Contact: Benjamin Kasenda, PD. Dr. Dr.; Phone Number: +41 61 265 50 75; Email: Benjamin.Kasenda@usb.ch
    • Principal Investigator: Benjamin Kasenda, PD. Dr. Dr.
  • Liestal, Switzerland, 4410
    • Recruiting
    • Kantonsspital Baselland
    • Contact: Bettina Seifert, Dr.; Phone Number: +41 61 925 27 15; Email: bettina.seifert@ksbl.ch
    • Principal Investigator: Bettina Seifert, Dr.
  • Saint Gallen, Switzerland, 9016
    • Recruiting
    • Tumor- und Brustzentrum Ostschweiz
    • Contact: Friedemann Honecker, PD Dr. Dr.; Phone Number: +41 71 243 02 02; Email: info@tbz-ost.ch
    • Principal Investigator: Friedemann Honecker, PD Dr. Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Locally advanced non-operable or metastatic solid tumor, except for skin cancer
• Eligible for routine (standard) treatment with immune checkpoint inhibitor (+/- chemo/targeted therapy) as per the discretion of the local investigator
• Subjects must be eligible for treatment with mistletoe preparations (controlled brain metastases, prednisolone equivalent below 10mg, no known hypersensitivity)
• ECOG (Eastern Cooperative Oncology Group) performance status score of 0-2
• Males and Females at least 18 years of age; no subjects under tutelage
• No previous mistletoe treatment

Exclusion Criteria:

• Contraindications to Iscador® Qu or immune checkpoint inhibitors, e.g. hypersensitivity, active autoimmune disorder
• Patients with skin cancer
• Participation in another study with investigational drug within 30 days prior to enrolment (participation in observational studies or diagnostic studies without a particular drug intervention are allowed)
• Enrolment of the investigator, his/her family members, employees and other dependent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A: Immune checkpoint inhibitors plus Iscador® Qu; Patients randomized to Arm A will be treated with Immune checkpoint inhibitors plus Iscador® Qu.	Drug: Immune checkpoint inhibitors plus Iscador® Qu.; Standard cancer treatment plus subcutaneous injection of mistletoe fermented extract (Iscador® Qu) as per the summary of product characteristics.
Active Comparator: Arm B: Immune checkpoint inhibitors; Patients randomized to Arm B will be treated with Immune checkpoint inhibitors only.	Drug: Immune Checkpoint Inhibitors; Standard cancer treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with a relative increase in T cell richness or diversity of 20% or more	Percentage of patients with a relative increase in T cell richness or diversity of 20% or more as measured by peripheral blood T cell receptor Next-generation sequencing.	baseline and 12 weeks (+/- 2 weeks)
Percentage of patients with a relative decrease in T cell clonality of 20% or more	Percentage of patients with a relative decrease in T cell clonality of 20% or more as measured by peripheral blood T cell receptor Next-generation sequencing.	baseline and 12 weeks (+/- 2 weeks)
Level of T cell richness	Level of T cell richness as measured by peripheral blood T cell receptor Next-generation sequencing.	baseline and 12 weeks (+/- 2 weeks)
Level of T cell diversity	Level of T cell diversity as measured by peripheral blood T cell receptor Next-generation sequencing.	baseline and 12 weeks (+/- 2 weeks)
Level of T cell clonality	Level of T cell clonality as measured by peripheral blood T cell receptor Next-generation sequencing.	baseline and 12 weeks (+/- 2 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival	up to 24 months
Rate of early immune checkpoint inhibitor-based treatment termination	Rate of early immune checkpoint inhibitor-based treatment termination	up to 24 months
Best tumor response	Best tumor response as per investigators assessment	up to 24 months
Progression-free survival	Investigator-assessed progression-free survival	up to 24 months
Safety and tolerability according to the NCI CTC AE v5	Safety and tolerability according to the NCI CTC AE v5 (National Cancer Institute Common Terminology Criteria for Adverse Events)	up to 18 weeks
EORTC QLQ C30	Quality of life as measured by EORTC QLQ C30 (European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire). Calculation of the scores follows the validated formulas as issued by the EORTC. Scores range from 0% to 100% for all questionnaire domains with higher values representing better outcome.	up to 24 months

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Benjamin Kasenda, PD Dr. Dr., USB

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: May 7, 2024
• First Submitted That Met QC Criteria: May 7, 2024
• First Posted (Actual): May 10, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Mistletoe Extract
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Antineoplastic Agents, Immunological; Anti-Infective Agents; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Immune Checkpoint Inhibitors; Viscum album peptide
• Other Study ID Numbers: 2023-02373; th23binder

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No