Investigation of the Timely-coordinated Therapy of Patients With Metastatic Cancer by Radiotherapy Together With Immune Checkpoint Inhibition

Metastatic Cancer Clinical Trial

— ST-ICI  

Official title:

Investigation of the Timely-coordinated Therapy of Patients With Metastatic Cancer by Radiotherapy Together With Immune Checkpoint Inhibition

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03453892
• Other study ID #: ST-ICI
• Status: Completed
• Start date: April 1, 2017
• Est. completion date: December 30, 2022

Study information

• Verified date: February 2023
• Source: University of Erlangen-Nürnberg Medical School
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Immunotherapy for the treatment of several cancer entities steadily increased during the last years. The data from the finalized and ongoing studies show the tremendous impact of immune checkpoint inhibition (ICI) also for advanced metastatic patients. Especially the ICI with pembrolizumab and nivolumab have an increasing number of first line treatment approvals. However, in particular metastatic patients which receive ICI therapy are often irradiated for immediate palliation of several metastases. Preclinical work revealed that radiotherapy (RT) is capable to modulate the tumor phenotype, its microenvironment in a way that systemic anti-tumor immune responses are induced. However, radiation has also immune suppressive properties as e.g. the expression of immune checkpoint molecules is increased following radiotherapy. So the ICI therapy in combination with the RT has the potential to overcome the immunotolerance of the tumor and the metastases. More and more reports therefore describe a so-called systemic immune-modulating effect of radiotherapy (former and still often named as abscopal effect). However the timely application of ICI and RT is often randomly and depends on the clinical need for the palliative RT. The aim of this trial is therefore to standardize the chronology of RT in combination with ICI, to evaluate the effects of radio-immunotherapy with a stratified and comparable patient cohort. The ST-ICI study is a prospective and observational study not influencing the standard therapeutic scheme and will provide hints how the radio-immune therapy drives systemic anti tumor responses.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: December 30, 2022
• Est. primary completion date: February 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients suffering and diagnosed for: metastatic cancer of several entities

• Clinical indicated therapy with PD-1/PD-L1 inhibitors or CTLA-4 antagonists

• Optionally radiotherapy if clinically indicated

• Age at least 18 years

Exclusion Criteria:

• fertile patients who refuse effective contraception during study treatment

• persistent drug and/or alcohol abuse

• patients not able or willing to behave according to study protocol

• patients in care

• patients that are not able to speak German

• patients which are imprisoned according to legal or governmental order

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis
• Neoplasms
• Neoplasms, Second Primary

Intervention

Drug:
• Nivolumab
The normal clinical treatment-plan of the underlying disease remains unchanged.
• Pembrolizumab
The normal clinical treatment-plan of the underlying disease remains unchanged.

Radiation:
• Radiotherapy
The normal clinical treatment-plan of the underlying disease remains unchanged.

Drug:
• Ipilimumab
The normal clinical treatment-plan of the underlying disease remains unchanged.

Locations

Country	Name	City	State
Germany	Department of Radiation Oncology, Universitätsklinikum Erlangen	Erlangen	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
University of Erlangen-Nürnberg Medical School

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Systemic (according to iRECIST criteria) and local response of detected metastases during radio and/or immunotherapy.		From date of inclusion to the trial until the date of first documented iRECIST progression or date of death from any cause, whichever came first, assessed up to day 540.
Primary	Change of circulating immune cells of treated patients by deep immunophenotyping.	Immunophenotyping of the patients: Detection of about 30 distinct immune sell (sub)types together with their activation markers. The analyses are conducted at time points before (day 0) and before every prescription of ICI (every 14 to 21 days) till progression or end of study at day 540.	The analyses are conducted at time points before (day 0) and before every prescription of ICI (every 14 to 21 days) till progression or end of study at day 540
Secondary	Detection of adverse events according to NCI CTAE (v4.0)		From date of inclusion to the trial until the date of first documented iRECIST progression or date of death from any cause, whichever came first, assessed up to day 540.
Secondary	Documentation of corticoid prescription		From date of inclusion to the trial until the date of first documented iRECIST progression or date of death from any cause, whichever came first, assessed up to day 540.
Secondary	Overall survival		Till death of the patient or end of study at day 540, whichever came first
Secondary	Progression free survival		From date of inclusion to the trial until the date of first documented iRECIST progression or date of death from any cause, whichever came first, assessed up to day 540.