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

Официальное название

Clinical Benefit and Biomarker Analysis of Combination of PD-1/PD-L1 Immune Checkpoint Inhibitors and Radiotherapy in NSCLC, HNSCC and Other Solid Tumors

Обзор

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

Вмешательства

• Другое 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.

Первичные конечные точки

• Overallsurvival [Срок оценки: From inclusion till death of subject or up to 5 years, whichever came first.]
• Longitudinal Immunophenotype [Срок оценки: Day 0 till progression or end of study up to 5 years or till change to conventional treatment without ICI, whichever came first.]
• Predictors in pattern recognition analyses [Срок оценки: Day 0 till progression or end of study up to 5 years or till change to conventional treatment without ICI, whichever came first.]
• Immune-associated side effects [Срок оценки: Day 0 till progression or end of study up to 5 years or till change to conventional treatment without ICI, whichever came first.]

Вторичные конечные точки (4)

• Detection of adverse events according to NCI CTAE (v4.0) [Срок оценки: 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.]
• Progression free survival [Срок оценки: 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]
• Treatment response (according to RECIST and iRECIST criteria) [Срок оценки: 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]
• Attempt to establish an immune matrix of responding/non-responding patients [Срок оценки: 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.]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Германия · 1 центр

• Department of Radiation Oncology, Universitätsklinikum Erlangen — Erlangen

Идентификаторы

NCT: NCT04892849 · ST-ICI02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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