Study for the Multidimensional Analyses of Resistance and Toxicity to Immune- and Targeted-therapies.

NCT06321640 | Recruiting

• 1 other identifier: IEO 1777
• Study Type: observational
• Target: 265
• Locations: 1 country
• Sites: 1

Brief Summary

Novel treatment modalities like targeted therapies and Immune checkpoint inhibitors have revolutionised the therapeutic landscape in oncology and hematology, significantly improving outcomes even in clinical contexts in which little improvement had been observed for decades such as metastatic melanoma, lung cancer, and lymphoproliferative neoplasms such as chronic lymphoid leukemia or Hodgkin lymphoma. However, major issues remain unsolved, given the frequent occurrence of primary or secondary resistance and the still incomplete understanding of the physiopathology of adverse events, which represent a major cause of morbidity and treatment interruption and often remain difficult to treat and diagnose. In this complex landscape, identifying the best treatment option for each patient remains challenging. For both targeted therapies and Immune checkpoint inhibitors, several biomarkers have been reported, but their implementation in clinical practice is still uncommon, and most of the decision-making process remains based on purely clinical considerations or constraints dictated by the regulatory bodies. Obstacles to biomarker-driven decision making are manifold and include insufficient understanding of the underlying biology, lack of strong evidence on their predictive power and limited tumor sampling, which may be circumvented by non-invasive techniques such as liquid biopsies.

Conditions

Breast Cancer; Lung Cancer; Melanoma; Head and Neck Cancer; Urothelial Carcinoma; Colorectal Cancer; Liver Metastases; Lung Metastases

Outcome Measures

Primary Outcomes (1)

• Percentage of patients in each cohort that will obtain a full "core" omic characterization.

  For cohorts A-E: i) Whole Exome Sequencing of tumor samples (biopsy/surgery) ii) ribonucleic acid sequence iii) Whole-genome "shotgun" metagenomic sequencing of fecal samples For cohorts C and D: i) Computation of the 11-parameter multivariable score: clonal Tumor Mutation Load, indel Tumor Mutation Load, nonsense mediated decay-escape Tumor Mutation Load, tobacco signature etc. For cohorts E,F i) High throughput cytokine bead array on plasma samples ii) ribonucleic acid sequence iii) Whole-genome "shotgun" metagenomic sequencing of fecal samples

  2 months

Secondary Outcomes (1)

• Percentage of patients with complete clinical data collection over the expected follow-up time and with successful biobanking.

  2 years

Study Arms (6)

Cohort A: primarily operable disease, candidate to adjuvant

This cohort includes any patient with nonmetastatic disease, candidate to surgery as primary treatment, for whom adjuvant therapy with targeted or immune therapy is recommended based on prior information obtained on the diagnostic biopsy. This cohort represents a control group, for whom high-throughput DNA/RNA sequencing is considered feasible in the vast majority of cases, and will not be considered in the computation of the primary endpoint. Small groups representative of relevant diseases will be collected, as follows: * Breast * Lung * Melanoma * Head and Neck * Urothelial * Colorectal cancer * Metastasectomy from lung or liver, from any cancer

Genetic: Cohort A: primarily operable disease, candidate to adjuvant

Cohort B: locally advanced disease

Patients in this cohort are eligible if diagnosed with or highly suspected of locally advanced (nonmetastatic) neoplasm and candidate to a diagnostic/confirmatory biopsy and subsequent treatment with targeted therapy, immune therapy or radiotherapy, where the treatment is administered with potentially curative intent. Patients in this cohort may be considered for enrolment prior to a formal diagnosis, so the study should be offered on the basis of a high suspicion of invasive cancer upon radiological evidence.Cohort B1: patients who, at the moment of biopsy, are expected to be subsequently treated with targeted therapy. Cohort B2: patients who, at the moment of biopsy, are expected to be subsequently treated with immune therapy. Cohort B3: patients who, at the moment of biopsy, are expected to be treated with combined chemo-immuno-radiotherapy

Genetic: Cohort B: locally advanced disease

Cohort C: metastatic disease

In this cohort, patients are eligible if diagnosed with invasive cancer with radiologically proven metastatic localization and candidate to treatment with targeted or immune therapy. Cohort C1: patients candidate to targeted therapy Cohort C2: patients candidate to immune therapy

Genetic: Cohort C: metastatic disease

Cohort D: Progressive disease

In this cohort, patients are eligible if a tumor biopsy is considered indicated by the referring physician upon disease progression to prior treatment in the metastatic setting or for hematological neoplasms. Definition of progression is based on the investigator's judgement and does not strictly require RECIST 1.1 definition, although all relevant radiological data will be collected whenever possible. Tumor biopsy must be collected no more than 6 months after the documented date of progression. Subgroups include: Cohort D1: progression disease to targeted. Patients whose last treatment at the moment of enrolment is a targeted agent. Cohort D2: progression disease to immune. Patients whose last treatment at the moment of enrolment is an immunotherapeutic agent Cohort D3: potential off-label treatment. Any patient that has exhausted standard treatment and that in the judgement of the investigator may benefit from an exome-wide mutational screen to identify actionable alterations

Genetic: Cohort D: Progressive disease

Cohort E: Hematological neoplasms

Cohort E1: Any patient that is expected to be treated with targeted agents. Special consideration will be given to patients affected by chronic lymphoid leukemia and follicular lymphoma treated with Bruton´s tyrosine kinase (BTK) inhibitor, Phosphoinositide 3-kinase inhibitor, B-cell lymphoma 2 inhibitor +/- monoclonal antibodies. Cohort E2: Any patient that is expected to be treated with immunotherapy. Special consideration will be given to patients affected by Hodgkin lymphoma and Diffuse Large B-cell lymphoma treated with Immune checkpoint inhibitors, Tafasitamab/Lenalidomide, immunoconjugates.

Genetic: Cohort E: Hematological neoplasms

Cohort F: Toxicity

In this cohort, patients are enrolled upon experiencing an adverse event of grade 3/4 as per Common Terminology Criteria for Adverse Events version 5.0 that, in the opinion of the investigator, is unequivocally caused by a targeted or immune therapeutic. The event may occur at any time after the last dose of the drug. Events may be of any nature but particular attention will be given to those events for which pathophysiology is currently poorly understood.Cohort F1: toxicity to Targeted therapy. Patients experiencing Grade 3-Grade 4 adverse events due to targeted therapy Cohort F2: toxicity to Immune therapy. Patients experiencing Grade 3-Grade 4 adverse events due to Immune therapy.

Genetic: Cohort F: Toxicity

Interventions

Cohort A: primarily operable disease, candidate to adjuvant GENETIC

This cohort includes any patient with nonmetastatic disease, candidate to surgery as primary treatment, for whom adjuvant therapy with targeted or immune therapy is recommended based on prior information obtained on the diagnostic biopsy. This cohort represents a control group, for whom high-throughput DNA/RNA sequencing is considered feasible in the vast majority of cases, and will not be considered in the computation of the primary endpoint

Cohort A: primarily operable disease, candidate to adjuvant

Cohort B: locally advanced disease GENETIC

Patients in this cohort are eligible if diagnosed with or highly suspected of locally advanced (nonmetastatic) neoplasm and candidate to a diagnostic/confirmatory biopsy and subsequent treatment with targeted therapy, immune therapy or radiotherapy, where the treatment is administered with potentially curative intent. Patients in this cohort may be considered for enrolment prior to a formal diagnosis, so the study should be offered on the basis of a high suspicion of invasive cancer upon radiological evidence.

Cohort B: locally advanced disease

Cohort C: metastatic disease GENETIC

In this cohort, patients are eligible if diagnosed with invasive cancer with radiologically proven metastatic localization and candidate to treatment with targeted or immune therapy.

Cohort C: metastatic disease

Cohort D: Progressive disease GENETIC

In this cohort, patients are eligible if a tumor biopsy is considered indicated by the referring physician upon disease progression to prior treatment in the metastatic setting or for hematological neoplasms. Definition of progression is based on the investigator's judgement and does not strictly require RECIST 1.1 definition, although all relevant radiological data will be collected whenever possible. Tumor biopsy must be collected no more than 6 months after the documented date of progression.

Cohort D: Progressive disease

Cohort E: Hematological neoplasms GENETIC

Any patient that is expected to be treated with targeted agents. Special consideration will be given to patients affected by chronic lymphoid leukemia and follicular lymphoma treated with BTKi, PI3Ki, BCL-2i +/- monoclonal antibodies. Any patient that is expected to be treated with immunotherapy. Special consideration will be given to patients affected by Hodgkin lymphoma and Diffuse Large B-cell lymphoma treated with ICIs, Tafasitamab/Lenalidomide, immunoconjugates.

Cohort E: Hematological neoplasms

Cohort F: Toxicity GENETIC

In this cohort, patients are enrolled upon experiencing an adverse event of grade 3/4 as per CTCAE v 5.0 that, in the opinion of the investigator, is unequivocally caused by a targeted or immune therapeutic. The event may occur at any time after the last dose of the drug. Events may be of any nature but particular attention will be given to those events for which pathophysiology is currently poorly understood (severe myocardial or neurologic Immune-related events or DS-8201-induced pneumonitis)

Cohort F: Toxicity

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patient with solid tumors

You may qualify if:

• age\>18 yrs old
• histological diagnosis of any cancer
• signed informed consent
• fulfills criteria described in cohort definition
• Clinical indication for a diagnostic biopsy

You may not qualify if:

• Performance Status (ECOG) \>2
• life expectancy \< 3 months
• unwilling to receive treatment at IEO for at least 6 months after enrolment
• active pregnancy at the moment of enrolment
• for cohort F: use of steroids (higher than 10 mg prednisone-equivalent) or other major immunosuppressive drug (e.g. tocilizumab) in the 14 days prior to the baseline sample collection.

Sponsors & Collaborators

• European Institute of Oncology: lead

Study Sites (1)

European Institute of oncology

Milan, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

A surgical specimen will be collected. The sample will be processed regularly for diagnostic histopathology.One additional tumor specimen beyond the diagnostic biopsy will be collected using a single-pass technique. If a single additional specimen is collected, it will be processed in formalin according to the standard pathology procedure.Peripheral blood (18 ml in total) and Bone Marrow Aspirate (10 ml) will be collected.A biological specimen relevant for the toxic event will be collected.

MeSH Terms

Conditions

Breast Neoplasms; Lung Neoplasms; Melanoma; Head and Neck Neoplasms; Carcinoma, Transitional Cell; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Luca Mazzarella

  European Institute of Oncology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luca Mazzarella

CONTACT

+390294375111; luca.mazzarella@ieo.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2024
• First Posted: March 20, 2024
• Study Start: July 8, 2022
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: March 20, 2024

Record last verified: 2024-03

Locations

IT (1)