A Prospective Dose Finding Study of Iscador Infusion

NCT04376931 | Unknown Phase 1

• 1 other identifier: ISINFULA 37-04
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Prospective, dose-escalating mono-center open label dose-finding study without control group (3+3 design), including a follow-up on-treatment observation. In this study will be recruited 15 patients with a histologically or cytologically confirmed diagnosis of an advanced malignant disease during a therapy-free interval.Investigational drug:Iscador®P: fermented aqueous extract of mistletoe grown on pine tree (Viscum album L. subspecies austriacum (Wiesb.) Vollmann), licensed for subcutaneous (SC) application in Switzerland, Germany, Austria, Sweden, and South Korea in dosages up to 20 mg. The initial dose group of the study is set to 40 mg Iscador®P.

Conditions

Advanced Cancer

Keywords

advanced malignant disease; mistletoe; Iscador

Outcome Measures

Primary Outcomes (1)

• Incidence of dose-limiting toxicities

  Maximum tolerated dose (MTD) of Iscador®P infusions, i.e. the dose eliciting dose-limiting toxicities (DLTs) in a maximum of 1 out of 6 patients treated at that dose.treated at that dose.

  Subjects will be in this study for up to 58 weeks ( 4 weeks of treatment and follow-up for a maximum of 52 weeks if subjects are deemed to have continuous clinical benefit from the Iscador®P infusions.

Secondary Outcomes (5)

• Quality of Life as Assessed Using Functional Assessment of Cancer Therapy - General (FACIT-G)

  Baseline and prior to each infusion in phase I and monthly in the follow-up period.4 weeks and follow up period for a maximum of 52 weeks

• Incidence of adverse drug reactions (ADRs).

  Subjects will be in this study for up to 58 weeks ( 4 weeks of treatment and follow-up for a maximum of 52 weeks if subjects are deemed to have continuous clinical benefit from the Iscador®P infusions.

• Tumor response

  4 weeks and follow up period for a maximum of 52 weeks

• Progression-free survival

  4 weeks and follow up period for a maximum of 52 weeks

• Overall survival

  4 weeks and follow up period for a maximum of 52 weeks

Study Arms (1)

Iscador®P as intravenous infusion

EXPERIMENTAL

Investigational therapy will be administered in six Dose Groups (DG): 10 mg, 20 mg, 40 mg, 90 mg, 140 mg and 200 mg Iscador®P. The initial dose group of the study is set to 40 mg Iscador®P. The two lower dose groups (20 or 10 mg) will only be used in case of intolerance at 40 mg Iscador®P. Once per week patients receive intravenous infusions of Iscador®P dissolved in 250 ml of sodium chloride solution (0.9 %). After the 4-week period of the MTD estimation phase each subject will immediately be included into a follow up observation in which he/she receives the last well tolerated dosage they had or the next lower dosage than the currently investigated DG in the running phase Ib study depending on the current estimate of the MTD at that time.

Drug: Intravenous Solution

Interventions

Intravenous Solution DRUG

Iscador®P: fermented aqueous extract of mistletoe grown on pine tree (Viscum album L. subspecies austriacum (Wiesb.) Vollmann), licensed for subcutaneous (SC) application in Switzerland, Germany, Austria, Sweden, and South Korea in dosages up to 20 mg.

Also known as: ISINFULA

Iscador®P as intravenous infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily given written informed consent.
• ≥18 years of age.
• Metastatic or locally advanced solid tumor, histologically or cytologically confirmed, no standard therapy available or standard therapy has failed.
• Adequate organ function
• Life expectancy ≥ 3 months, ECOG ≤ 2.
• No ongoing or preceding therapy with mistletoe products.
• Women of childbearing potential: negative serum pregnancy test at screening, use of two adequate barrier methods
• Compliance with protocol, legal competence.

You may not qualify if:

• \- Systemic cytotoxic chemotherapy, biological therapy, radiation therapy, OR major surgery prior trial treatment.
• Persisting toxicity of NCI-CTCAE Grade \>1 related to prior therapy (Sensory neuropathy of Grade ≤2 is acceptable).
• Expected to require any other form of systemic or localized antineoplastic therapy while on trial
• Systemic corticosteroid therapy received ≤ 3 days prior to trial treatment or other forms of systemic immunosuppressive medication (except corticosteroids against immune-related AEs and /or premedication for IV contrast allergies/reactions; corticosteroid replacement therapy)
• Tumor and/or metastases of the CNS and/or carcinomatous meningitis
• Active infection requiring intravenous systemic therapy, HIV, severe allergic illness (including asthma), active tuberculosis, inflammatory diseases with body temperature \> 38° C.
• Known hypersensitivity to mistletoe products.

Sponsors & Collaborators

• HaEmek Medical Center, Israel: lead

Study Sites (1)

Haemek MC

Afula, North, Israel

Location

Study Officials

• Gil Bar Sela, Prof

  Haemek MC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gil Bar Sela, Prof

CONTACT

+97250-206-1207; gil_ba@clalit.org.il

Ela Lutwak, M.SC

CONTACT

+972546459510; ella_lu@clalit.org.il

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, dose-escalating mono-center open label dose-finding study without control group (3+3 design), including a follow-up on-treatment observation.

Study Record Dates

• First Submitted: April 30, 2020
• First Posted: May 6, 2020
• Study Start: December 1, 2020
• Primary Completion: July 1, 2022
• Study Completion: July 1, 2023
• Last Updated: July 29, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)