Clinical Benefit and Biomarker Analysis of Combination of PD-1/PD-L1 Immune Checkpoint Inhibitors and Radiotherapy

Esophageal Cancer Clinical Trial

— ST-ICI02  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04892849
• Other study ID #: ST-ICI02
• Status: Recruiting
• Start date: April 30, 2021
• Est. completion date: December 31, 2027

Study information

• Verified date: February 2023
• Source: University of Erlangen-Nürnberg Medical School
• Contact: Markus Hecht, PD Dr.
• Phone: +49 9131 85
• Email: markus.hecht[@]uk-erlangen.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2027
• Est. primary completion date: May 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Bronchogenic
• Carcinoma, Renal Cell
• Esophageal Cancer
• HNSCC
• NSCLC
• Renal Cell Carcinoma
• Squamous Cell Carcinoma of the Skin
• Urothelial Carcinoma

Intervention

Other:
• Conventional Therapy acc. to prevailing clincal approved schemes
The study is observational. The treatment-plan of the underlying disease remains unchanged. The treatment of the patient is according to the prevailing clinical approved schemes at the respective entities. Blood will be drawn from patients at several time points during and after RT and ICI for detailed immunomonitoring of the patients.

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	Overallsurvival	Prospective investigation of the survival of the patients.	From inclusion till death of subject or up to 5 years, whichever came first.
Primary	Longitudinal Immunophenotype	Longitudonal Immunophenotyping of the patients: Detection of about 30 distinct immune cell (sub)types together with their activation markers during treatement.	Day 0 till progression or end of study up to 5 years or till change to conventional treatment without ICI, whichever came first.
Primary	Predictors in pattern recognition analyses	Identification of possible predictors in pattern recognition analyses from clinical imaging data sets.	Day 0 till progression or end of study up to 5 years or till change to conventional treatment without ICI, whichever came first.
Primary	Immune-associated side effects	Detection of immune-associated side effects	Day 0 till progression or end of study up to 5 years or till change to conventional treatment without ICI, whichever came first.
Secondary	Detection of adverse events according to NCI CTAE (v4.0)	The adverse effects of Immunecheckpoint and Radiotherapy is recorded by official questionaire	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.
Secondary	Progression free survival	survival of the patient without progression of malignant disesase	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
Secondary	Treatment response (according to RECIST and iRECIST criteria)	RECIST and iRECIST criteria will used to analyse the response of the patient to the respective treatement	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
Secondary	Attempt to establish an immune matrix of responding/non-responding patients	Analysis of clincal, MRI and imunnologic, molecular data to develop an biomarkermatrix with processes of machine learning	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.