Clinical trial NCT03453892: Investigation of the Timely-coordinated Therapy of Patients With Metastatic Cancer by Radiotherapy Together With Immune Checkpoint Inhibition
Official title: Investigation of the Timely-coordinated Therapy of Patients With Metastatic Cancer by Radiotherapy Together With Immune Checkpoint Inhibition
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Metastatic Cancer
Keywords: Metastatic cancer
Radiotherapy
Immunotherapy
radioimmuno therapy
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
First posted: 2018-03-05
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study cohort consist of patients suffering from metastatic cancer of several entities which will be treated with optionally RT (if indicated) and/or ICI at Department of Radiation Oncology of Universitätsklinikum Erlangen.

Both gender are included into the study, a maximum age was not defined.

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.


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

Primary outcomes:
measure: Systemic (according to iRECIST criteria) and local response of detected metastases during radio and/or immunotherapy.
timeFrame: 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.
measure: Change of circulating immune cells of treated patients by deep immunophenotyping.
timeFrame: 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 outcomes:
measure: Detection of adverse events according to NCI CTAE (v4.0)
timeFrame: 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.
measure: Documentation of corticoid prescription
timeFrame: 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.
measure: Overall survival
timeFrame: Till death of the patient or end of study at day 540, whichever came first
measure: Progression free survival
timeFrame: 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.
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: Department of Radiation Oncology, Universitätsklinikum Erlangen
state: Bavaria
Study officials:
affiliation: Department of Radiation Oncology, Universitätsklinikum Erlangen
name: Rainer Fietkau, Prof. Dr.
role: STUDY_CHAIR
affiliation: Department of Radiation Oncology, Universitätsklinikum Erlangen
name: Markus Hecht, Dr. med.
role: STUDY_DIRECTOR
affiliation: Department of Radiation Oncology, Universitätsklinikum Erlangen
name: Udo S Gaipl, Prof. Dr.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.