Clinical trial NCT04025424: Genetic Predictors of Efficiency and Safety of ICIs in Patients With Different Malignancies (ICIPRESIST-0519)
Official title: Observational Study of Genetic Predictors of Efficiency and Safety of Immune Checkpoints Inhibitors in Patients With Different Malignancies (ICIPRESIST-0519)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Melanoma
Squamous Cell Lung Cancer
Uveal Melanoma
Hodgkin Lymphoma
Lead sponsor: Russian Academy of Medical Sciences
Sponsor class: OTHER
First posted: 2019-07-18
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The target sample consists of approximately 350 treated patients, treatment of patients with melanoma, squamous cell lung cancer in the late stages (inoperable or metastatic) and Hodgkin dsisease, who met the criteria.

The current study will be conducted in selected research centers where at least 5 patients are treated with blockers of immune checkpoints during the quarter (3 months) in the period from 2015 to 2019. In each research center, patients will be identified that meet the inclusion criteria, based on the lists of patients who received therapy with blockers of immune checkpoints in specific research centers. The study is conducted only in centers located in Russia.

Brief summary: This is a multicenter, non-interventional, retrospective study (with two prospective cohorts), including previously treated patients with melanoma, squamous cell lung cancer in the late stages (inoperable or metastatic) and Hodgkin disease at any stages.

The duration of the follow-up will be 12-60 months. Data from medical records will be retrospectively collected at different points in time. The first data extraction will consist of collecting data from the initial level (before treatment with immune checkpoints inhibitors (anti-PD1 / PDl1) before the end of the recruitment period for this study (up to 3 years of follow-up). Two additional annual data collections are planned for display additional follow-up and data for patients who will survive.


Eligibility criteria: Inclusion Criteria:

To participate in this study, the patient must meet the following criteria:

* At least 2 injections (or 10 weeks) of ICI (PD1, PDl1 blockers, including but not limited to such drugs as nivolumab, pembrolizumab, prolglimab, atezolizumab, avelumab, durvalumab, spratalizumab)
* Deceased patients meet the criteria; signing the informed consent of the legal representative of the deceased patient is not required

Specific inclusion criteria for individual cohorts:

* Cohort 1 (retrospective cohort of skin melanoma patients)

  * 1) Clinically and morphologically verified diagnosis of skin melanoma or melanoma metastases without an identified primary focus;
  * 2) The availability of basic clinical information about the patient and the course of his illness;
  * 3) Therapy with a PD-1 or PD-L1 inhibitor in the standard dosage in monotherapy (at least 2 injections);
  * 4) Evaluation of the effect of immunotherapy
  * 5) Availability of tumor material (paraffin blocks) for morphological, immunohistochemical and molecular genetic studies, obtained no earlier than 24 months. before initiating therapy with a PD-1 or PD-L1 inhibitor;
  * 8) Patient-signed informed consent in case the patient is alive
* Cohort 2 (Hodjkin disease - retrospective)

  * 1) Clinically and morphologically verified diagnosis of Hodgkin disease (any histological variant);
  * 2) The availability of basic clinical information about the patient and the course of his illness;
  * 3) Availability of tumor material (paraffin blocks) for morphological, immunohistochemical and molecular genetic studies;
  * 4) Patient signed informed consent.
* Cohort 3 (Uveal melanoma - retro)

  * 1) Clinically and morphologically verified diagnosis of uveal melanoma (any histological variant);
  * 2) The availability of basic clinical information about the patient and the course of his illness;
  * 3) Availability of tumor material (paraffin blocks) for morphological, immunohistochemical and molecular genetic studies;
  * 4) Patient signed informed consent.
* Cohort 4 (melanoma of the skin - prospective)

  * 1) Clinically and morphologically verified diagnosis of metastatic melanoma;
  * 2) The availability of basic clinical information about the patient and the course of his illness;
  * 3) Indications for therapy with a PD-1 or PD-L1 inhibitor in the standard dosage in monotherapy;
  * 4) The possibility of including the patient in the present study before the first course of immunotherapy;
  * 5) Availability of tumor material (paraffin blocks and histological glass preparations) for morphological, immunohistochemical and molecular genetic studies obtained no earlier than 2 years before the planned start of immunotherapy with a standard PD-1 inhibitor;
  * 6) Separate patient consent to a repeated biopsy of the tumor focus before the planned start of immunotherapy with a PD-1 or PD-L1 inhibitor, if the existing tumor material was obtained earlier than 2 years before the planned start of immunotherapy
  * 7) Availability of samples of biological fluids collected before the start of immunotherapy and after the first course of immunotherapy for molecular genetic studies of circulating tumor DNA;
  * 8) Evaluation of the effect of therapy in the framework of local practice in accordance with the criteria of RECIST 1.1
  * 9) Signed by the patient informed consent to participate in the study.
* Cohort 5 (squamous cell lung cancer - prospective)

  * 1) Clinically and morphologically verified diagnosis of metastatic or inoperable squamous cell lung cancer;
  * 2) The availability of basic clinical information about the patient and the course of his illness;
  * 3) The presence of indications for therapy with a PD-1 or PD-L1 inhibitor in the standard dosage in monotherapy;
  * 4) The possibility of including the patient in the present study before the first course of immunotherapy;
  * 5) Availability of tumor material (paraffin blocks) for morphological, immunohistochemical and molecular genetic research, obtained no earlier than 2 years before the planned start of immunotherapy with a standard PD-1 inhibitor;
  * 6) Separate patient consent to a repeated biopsy of the tumor focus before the planned start of immunotherapy with a PD-1 or PD-L1 inhibitor, if the existing tumor material was obtained earlier than 2 years before the planned start of immunotherapy
  * 7) Availability of samples of biological fluids collected before the start of immunotherapy and after the first course of immunotherapy for molecular genetic studies of circulating tumor DNA;
  * 8) Evaluation of the effect of therapy in the framework of local practice in accordance with the criteria of RECIST 1.1
  * 9) Signed by the patient informed consent to participate in the study.

Exclusion Criteria:

* Cohort 1 (retrospective cohort of skin melanoma patients)

  - 1) It is not allowed to conduct other immunotherapy (anti-CTLA4, vaccines, etc.) to patients before the course of therapy with a PD-1 or PD-L1 inhibitor in a standard dosage in monotherapy
* Cohort 2 (Hodgkin disease - retrospective)
* no special exclusion criteria
* Cohort 3 (Uveal melanoma - retro)

  - No special exclusion criteria.
* Cohort 4 (melanoma of the skin - prospective)

  * 1) It is not allowed to include patients who have previously undergone other immunotherapy (anti-CTLA4, vaccines, etc.) before the course of therapy with the PD-1 or PD-L1 inhibitor in the standard dosage in monotherapy
  * 2) It is not allowed to include patients who are scheduled for combination immunotherapy (anti-PD1 + anti-CTLA4, vaccines, etc.) after inclusion in this study
* Cohort 5 (squamous cell lung cancer - prospective)

  * 1) It is not allowed to include patients who have previously undergone other immunotherapy (anti-CTLA4, vaccines, etc.) before the course of therapy with the PD-1 or PD-L1 inhibitor in the standard dosage in monotherapy
  * 2) It is not allowed to include patients who are scheduled for combination immunotherapy (anti-PD1 + anti-CTLA4, vaccines, etc.) after inclusion in this study.

Primary outcomes:
measure: overall survival (OS) of patients receiving immune checkpoint blockers (PD1 / PDl1 blockers) in the first and subsequent treatment lines in patients with metastatic or unresectable melanoma, lung cancer and lymphoma granulomatosis
timeFrame: dec 2021
measure: incidence and severity of all adverse events (AEs) in patients receiving immune checkpoint blockers (PD1 / PDl1 blockers) in the first and subsequent treatment lines in patients with metastatic or unresectable melanoma, lung cancer and lymphoma.
timeFrame: dec 2021
Secondary outcomes:
Other outcomes:
measure: progression-free survival (PFS) in patients receiving immune checkpoint blockers (PD1 / PDl1 blockers) in the first and subsequent treatment lines in patients with metastatic or unresectable melanoma, lung cancer and Hodgkin disease
timeFrame: dec 2021
measure: response rate in patients receiving immune checkpoint blockers (PD1 / PDl1 blockers) in the first and subsequent treatment lines in patients with metastatic or unresectable melanoma, lung cancer and Hodgkin disease
timeFrame: dec 2021
measure: Development of predictive molecular testing tools
timeFrame: dec 2021
Locations:
city: Moscow'
country: Russian Federation
facility: N.N. Blokhin Russian Cancer Research Center
state: Москва
Study officials:
References: