Clinical trial NCT04892849: Clinical Benefit and Biomarker Analysis of Combination of PD-1/PD-L1 Immune Checkpoint Inhibitors and Radiotherapy
Official title: Clinical Benefit and Biomarker Analysis of Combination of PD-1/PD-L1 Immune Checkpoint Inhibitors and Radiotherapy in NSCLC, HNSCC and Other Solid Tumors
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: HNSCC
NSCLC
Esophageal Cancer
Urothelial Carcinoma
Renal Cell Carcinoma
Squamous Cell Carcinoma of the Skin
Small Cell Bronchial Carcinomas
Keywords: Immunotherapy
Radiotherapy
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
First posted: 2021-05-19
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study cohort consist of patients suffering from HNSCC (palliative), NSCLC (separately palliative and adjuvant) and "other solid tumors" (including in particular esophageal carcinomas, urothelial and renal carcinomas, small cell bronchial carcinomas and squamous cell carcinomas of the skin \[depending on the current drug approval\]) which will be treated with ICI (PD-1/PD-L1) and potential radiation of metastases at Department of Radiation Oncology of Universitätsklinikum Erlangen.

Brief summary: Inhibitors of the programmed cell death protein 1 (PD-1)/PD-L1 immune checkpoint signaling pathway are already approved in the treatment of various tumor entities in relapsed or metastatic stages. Different exploratory trials suggest that the combination of radiotherapy and PD-1/PD-L1 inhibitors is highly effective, especially in oligometastatic stages and if all lesions are treated with ablative radiotherapy. In addition, the role of predictive biomarkers is becoming increasingly important for future therapy algorithms. First data, also from our group, indicate clearly that dynamic changes of immune cells and their activation markers in the peripheral blood (immune matrix) can be used as predictive biomarkers. During the planned STICI-02 trial predictive immune matrix derived from the STICI01 trial (NCT03453892) will be validated in the groups of patient suffering from HNSCC (palliative), NSCLC (separately palliative and adjuvant) and "other solid tumors" (including in particular esophageal carcinomas, urothelial and renal carcinomas, small cell bronchial carcinomas and squamous cell carcinomas of the skin \[depending on the current drug approval\]). Within the framework of scientific accompanying projects, the predictive value of markers in tumor tissue and of pattern radiomics analyses will be analyzed accompanying the immunophenotyping in peripheral blood. The side effects


Eligibility criteria: Inclusion Criteria:

* Patients treatable for HNSCC (palliative), NSCLC (separately palliative and adjuvant) or "other solid tumour"
* Indication for system therapy with a PD-1/PD-L1 inhibitor according to clinical standards
* Patients without or with radiation of one or more metastases
* Age at least 18 years

Exclusion Criteria:

* Melanoma patients
* 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

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

Primary outcomes:
measure: Overallsurvival
timeFrame: From inclusion till death of subject or up to 5 years, whichever came first.
measure: Longitudinal Immunophenotype
timeFrame: Day 0 till progression or end of study up to 5 years or till change to conventional treatment without ICI, whichever came first.
measure: Predictors in pattern recognition analyses
timeFrame: Day 0 till progression or end of study up to 5 years or till change to conventional treatment without ICI, whichever came first.
measure: Immune-associated side effects
timeFrame: Day 0 till progression or end of study up to 5 years or till change to conventional treatment without ICI, whichever came first.
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, or till change to conventional treatment , whichever came first, assessed up to 5 years.
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 5 yeras
measure: Treatment response (according to RECIST and iRECIST criteria)
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 5 years
measure: Attempt to establish an immune matrix of responding/non-responding patients
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 up to 5 years or till change to conventional treatment without ICI.
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: Department of Radiation Oncology, Universitätsklinikum Erlangen
state: Bavaria
Study officials:
affiliation: Universitätsklinikum Erlangen, Department of Radiation Oncology
name: Markus Hecht, PD Dr.
role: STUDY_DIRECTOR
affiliation: Universitätsklinikum Erlangen, Department of Radiation Oncology
name: Udo S Gaipl, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitätsklinikum Erlangen, Department of Radiation Oncology
name: Rainer Fietkau, Prof. Dr.
role: STUDY_CHAIR
affiliation: Universitätsklinikum Erlangen, Department of Radiation Oncology
name: Benjamin Frey, PD Dr. Dr.
role: PRINCIPAL_INVESTIGATOR
References: