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

NCT ID: NCT03453892

Last Updated: 2023-02-16

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 150 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-04-01
• Study Completion Date: 2022-12-30

Brief 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.

Conditions

Metastatic Cancer

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

anti CTLA-4

The study cohort consist of patients suffering from metastatic cancer of several entities which will be treated with palliative RT and/or ICI (anti CTLA-4) at Department of Radiation Oncology of Universitätsklinikum Erlangen.

Radiotherapy

Intervention Type: RADIATION

The normal clinical treatment-plan of the underlying disease remains unchanged.

Ipilimumab

Intervention Type: DRUG

The normal clinical treatment-plan of the underlying disease remains unchanged.

anti PD-1/PD-L1

The study cohort consist of patients suffering from metastatic cancer of several entities which will be treated with palliative RT and/or ICI (anti PD-1/PD-L1) at Department of Radiation Oncology of Universitätsklinikum Erlangen.

Nivolumab

Intervention Type: DRUG

The normal clinical treatment-plan of the underlying disease remains unchanged.

Pembrolizumab

Intervention Type: DRUG

The normal clinical treatment-plan of the underlying disease remains unchanged.

Radiotherapy

Intervention Type: RADIATION

The normal clinical treatment-plan of the underlying disease remains unchanged.

Interventions

Nivolumab

The normal clinical treatment-plan of the underlying disease remains unchanged.

Intervention Type: DRUG

Pembrolizumab

The normal clinical treatment-plan of the underlying disease remains unchanged.

Intervention Type: DRUG

Radiotherapy

The normal clinical treatment-plan of the underlying disease remains unchanged.

Intervention Type: RADIATION

Ipilimumab

The normal clinical treatment-plan of the underlying disease remains unchanged.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rainer Fietkau, Prof. Dr.

Role: STUDY_CHAIR

Department of Radiation Oncology, Universitätsklinikum Erlangen

Markus Hecht, Dr. med.

Role: STUDY_DIRECTOR

Department of Radiation Oncology, Universitätsklinikum Erlangen

Udo S Gaipl, Prof. Dr.

Role: STUDY_DIRECTOR

Department of Radiation Oncology, Universitätsklinikum Erlangen

Locations

Department of Radiation Oncology, Universitätsklinikum Erlangen

Erlangen, Bavaria, Germany

Countries

Germany

References

Griewing LM, Schweizer C, Schubert P, Rutzner S, Eckstein M, Frey B, Haderlein M, Weissmann T, Semrau S, Gostian AO, Muller SK, Traxdorf M, Iro H, Zhou JG, Gaipl US, Fietkau R, Hecht M. Questionnaire-based detection of immune-related adverse events in cancer patients treated with PD-1/PD-L1 immune checkpoint inhibitors. BMC Cancer. 2021 Mar 24;21(1):314. doi: 10.1186/s12885-021-08006-0.

Reference Type: DERIVED

PMID: 33761922 (View on PubMed)

Zhou JG, Donaubauer AJ, Frey B, Becker I, Rutzner S, Eckstein M, Sun R, Ma H, Schubert P, Schweizer C, Fietkau R, Deutsch E, Gaipl U, Hecht M. Prospective development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with recurrent/metastatic cancer to immune checkpoint inhibitors. J Immunother Cancer. 2021 Feb;9(2):e001845. doi: 10.1136/jitc-2020-001845.

Reference Type: DERIVED

PMID: 33593828 (View on PubMed)

Other Identifiers

ST-ICI

Identifier Type: -

Identifier Source: org_study_id