Breast CancerPOSITiveNCT06321640
Study for the Multidimensional Analyses of Resistance and Toxicity to Immune- and Targeted-therapies.
An observational study of Breast Cancer and Lung Cancer, run by European Institute of Oncology at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Breast Cancer, Lung Cancer, Melanoma
- What is being tested?
- Cohort A: primarily operable disease, candidate to adjuvant, Cohort B: locally advanced disease and Cohort C: metastatic disease
- How many people
- 265 participants
- Where
- 1 siteItaly
- Study dates
- 8 Jul 2022to 31 Dec 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patient with solid tumors
Who may be able to join
- age>18 yrs old
- histological diagnosis of any cancer
- signed informed consent
- fulfills criteria described in cohort definition
- Clinical indication for a diagnostic biopsy
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
European Institute of oncology
Milan
Giuseppe Curigliano
About this study
Official title: POSITive: Prospective Observational Study for the Multidimensional Analyses of Resistance and Toxicity to Immune- and Targeted-therapies
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.
Read the detailed description
Biomarkers to predict response and toxicity to Targeted Therapies. Targeted therapies such as kinase inhibitors are usually associated with extremely elevated response rates, precisely because their use requires the prior detection of a companion biomarker. However, secondary resistance almost invariably develops, resulting in often moderate improvements in overall survival despite major delays in disease progression. Resistance mechanisms can be broadly classified in two groups: i) "cis"-mutations that directly impinge on the binding of the drug to its target and ii) "trans" alterations that activate additional pathways able to override drug-induced inhibition or transcriptional upregulation of parallel pathways . In both cases these mutations are mostly acquired as an evolutionary response to the selective environment generated by the drug itself, and their identification is crucial to identify potential subsequent treatments able to circumvent the resistance mechanism. As more targeted therapies enter clinical practice, including novel classes like Antibody-drug conjugates (which maintain high target specificity but have completely different mechanisms of action), extensive investigation of the molecular mechanisms associated with secondary resistance becomes more and more relevant.
Furthermore, many targeted therapies are associated with specific toxicities such as interstitial lung disease that are themselves poorly characterized from a mechanistic point of view, and this lack of knowledge prevents effective diagnosis and treatment.
Biomarkers to predict response and toxicity to Immune Checkpoint Inhibitors. Several biomarkers with predictive power in Immune checkpoint inhibitorsI-treated patients have been reported (e.g. tumor mutational burden, extent of tumour T-cell infiltration at baseline, expression by tumor cells of the respective Immune checkpoint inhibitors targets). However each of these, individually, bears very little accuracy for outcome . A recent meta-analysis of tumor-intrinsic data across >1,000 patients and multiple tumor types elaborated a multivariable predictive model for each cancer type using 11 features derived from genomic (whole exome sequencing ) and transcriptomic (total ribonucleic acid sequencing ) data of primary tumors (see below for the list of markers). The multivariable predictor attained an Afea Under the Receiver-Operating Characteristic value of 0.86, thus strongly indicating that an integrated assessment of multiple and novel biomarkers achieves an accuracy that can significantly impact on decision making. Moreover, recent findings suggest a critical role for the gut microbiome. Notably, specific species in the gut microbiota promote anti-cancer immunity during Immune checkpoint inhibitors treatment, which can be transferred by faecal microbiome transplantation to rescues Immune checkpoint inhibitors sensitivity in model systems . Underlying molecular mechanisms, however, are unknown, and may involve immunological mimicry of tumour neoantigens by microbial peptides from the gut or tumor microbiota .
The issue of drug-related toxicities (Immune-related Adverse events) is possibly even more crucial in Immune checkpoint inhibitors-treated patients. Immune-related Adverse events commonly develop after a long latency, are associated with significant morbidity and mortality and often represent a reason for treatment discontinuation and disease relapse. Immune-related Adverse events are often difficult to diagnose, since their pathophysiology is different from that of clinically similar idiopathic autoimmune disorders. Despite the definition of consensus guidelines on the diagnosis and treatment of Immune-related Adverse events, therapeutic options are limited and invariably include generalized immune suppression, to the detriment of the anticancer response. Biomarkers strongly predictive or diagnostic of Immune-related Adverse events have not been identified to date. Some studies have identified specific cytokine combinations but these studies remain correlative and require validation in larger cohorts and different clinical contexts.
- Conditions
- Breast Cancer, Lung Cancer, Melanoma, Head and Neck Cancer, Urothelial Carcinoma, Colorectal Cancer
- Being tested
- Cohort A: primarily operable disease, candidate to adjuvant, Cohort B: locally advanced disease, Cohort C: metastatic disease, Cohort D: Progressive disease, Cohort E: Hematological neoplasms
- Medical subject headings
- Breast Neoplasms, Lung Neoplasms, Melanoma, Head and Neck Neoplasms, Carcinoma, Transitional Cell, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cohort A: primarily operable disease, candidate to adjuvantGenetic
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 B: locally advanced diseaseGenetic
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 C: metastatic diseaseGenetic
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 D: Progressive diseaseGenetic
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 E: Hematological neoplasmsGenetic
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 F: ToxicityGenetic
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)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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. Receives: 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. Receives: Genetic: Cohort F: Toxicity |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients in each cohort that will obtain a full "core" omic characterization.
For cohorts A-E:
- 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:
- 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
Measured: 2 months
Secondary outcomes (1)
Percentage of patients with complete clinical data collection over the expected follow-up time and with successful biobanking.
Percentage of patients with complete clinical and laboratory data collection over the expected follow-up time (2 years); Percentage of patients with successful biobanking (presence of at least 1 frozen tumor sample, 1 vial of EDTA blood, 2 vials of plasma at T0, T1, T2, 1 vial of feces at T0, T1, T2).Somatic mutations associated with sensitivity, primary/secondary resistance and toxicity;Prevalence of specific signaling-pathway transcriptional-activation signatures associated with sensitivity, primary/secondary resistance and toxicity;Prevalence of specific microbiota signatures associated with sensitivity, primary/secondary resistance and toxicity; Prevalence of germline variants associated with sensitivity, primary/secondary resistance and toxicity;
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2024
- Study start8 Jul 2022
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by European Institute of OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 265 participants (estimated)
Sponsor and investigators
- Lead sponsor
- European Institute of Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Luca Mazzarella, Principal investigator, European Institute of Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06321640
- Sponsor's protocol ID
- IEO 1777
- Acronym
- POSITive
- Status last verified
- Mar 2024
- First submitted
- 13 Mar 2024
- Last updated
- 20 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- POSITive: Prospective Observational Study for the Multidimensional Analyses of Resistance and Toxicity to Immune- and Targeted-therapies
- ClinicalTrials.gov ID
- NCT06321640
- Acronym / sponsor ID
- POSITive / IEO 1777
- Conditions
- Breast Cancer, Lung Cancer, Melanoma, Head and Neck Cancer, Urothelial Carcinoma, Colorectal Cancer
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 265 participants (estimated)
- Lead sponsor
- European Institute of OncologyUniversity, hospital or other
- Study start
- 8 Jul 2022 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 20 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Biomarkers to predict response and toxicity to Targeted Therapies. Targeted therapies such as kinase inhibitors are usually associated with extremely elevated response rates, precisely because their use requires the prior detection of a companion biomarker. However, secondary resistance almost invariably develops, resulting in often moderate improvements in overall survival despite major delays in disease progression. Resistance mechanisms can be broadly classified in two groups: i) "cis"-mutations that directly impinge on the binding of the drug to its target and ii) "trans" alterations that activate additional pathways able to override drug-induced inhibition or transcriptional upregulation of parallel pathways . In both cases these mutations are mostly acquired as an evolutionary response to the selective environment generated by the drug itself, and their identification is crucial to identify potential subsequent treatments able to circumvent the resistance mechanism. As more targeted therapies enter clinical practice, including novel classes like Antibody-drug conjugates (which maintain high target specificity but have completely different mechanisms of action), extensive investigation of the molecular mechanisms associated with secondary resistance becomes more and more relevant.
Furthermore, many targeted therapies are associated with specific toxicities such as interstitial lung disease that are themselves poorly characterized from a mechanistic point of view, and this lack of knowledge prevents effective diagnosis and treatment.
Biomarkers to predict response and toxicity to Immune Checkpoint Inhibitors. Several biomarkers with predictive power in Immune checkpoint inhibitorsI-treated patients have been reported (e.g. tumor mutational burden, extent of tumour T-cell infiltration at baseline, expression by tumor cells of the respective Immune checkpoint inhibitors targets). However each of these, individually, bears very little accuracy for outcome . A recent meta-analysis of tumor-intrinsic data across >1,000 patients and multiple tumor types elaborated a multivariable predictive model for each cancer type using 11 features derived from genomic (whole exome sequencing ) and transcriptomic (total ribonucleic acid sequencing ) data of primary tumors (see below for the list of markers). The multivariable predictor attained an Afea Under the Receiver-Operating Characteristic value of 0.86, thus strongly indicating that an integrated assessment of multiple and novel biomarkers achieves an accuracy that can significantly impact on decision making. Moreover, recent findings suggest a critical role for the gut microbiome. Notably, specific species in the gut microbiota promote anti-cancer immunity during Immune checkpoint inhibitors treatment, which can be transferred by faecal microbiome transplantation to rescues Immune checkpoint inhibitors sensitivity in model systems . Underlying molecular mechanisms, however, are unknown, and may involve immunological mimicry of tumour neoantigens by microbial peptides from the gut or tumor microbiota .
The issue of drug-related toxicities (Immune-related Adverse events) is possibly even more crucial in Immune checkpoint inhibitors-treated patients. Immune-related Adverse events commonly develop after a long latency, are associated with significant morbidity and mortality and often represent a reason for treatment discontinuation and disease relapse. Immune-related Adverse events are often difficult to diagnose, since their pathophysiology is different from that of clinically similar idiopathic autoimmune disorders. Despite the definition of consensus guidelines on the diagnosis and treatment of Immune-related Adverse events, therapeutic options are limited and invariably include generalized immune suppression, to the detriment of the anticancer response. Biomarkers strongly predictive or diagnostic of Immune-related Adverse events have not been identified to date. Some studies have identified specific cytokine combinations but these studies remain correlative and require validation in larger cohorts and different clinical contexts.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort A: primarily operable disease, candidate to adjuvant | – | Genetic: Cohort A: primarily operable disease, candidate to adjuvantThis 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 |
| Cohort B: locally advanced disease | – | Genetic: Cohort B: locally advanced diseasePatients 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 |
| Cohort C: metastatic disease | – | Genetic: Cohort C: metastatic diseaseIn 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 |
| Cohort D: Progressive disease | – | Genetic: Cohort D: Progressive diseaseIn 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 |
| Cohort E: Hematological neoplasms | – | Genetic: Cohort E: Hematological neoplasmsCohort 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. |
| Cohort F: Toxicity | – | Genetic: Cohort F: ToxicityIn 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patient with solid tumors
Key inclusion criteria (5 listed)
- age>18 yrs old
- histological diagnosis of any cancer
- signed informed consent
- fulfills criteria described in cohort definition
- Clinical indication for a diagnostic biopsy
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cohort A: primarily operable disease, candidate to adjuvantThis 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 | Genetic | Cohort A: primarily operable disease, candidate to adjuvant |
| Cohort B: locally advanced diseasePatients 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. | Genetic | Cohort B: locally advanced disease |
| Cohort C: metastatic diseaseIn this cohort, patients are eligible if diagnosed with invasive cancer with radiologically proven metastatic localization and candidate to treatment with targeted or immune therapy. | Genetic | Cohort C: metastatic disease |
| Cohort D: Progressive diseaseIn 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. | Genetic | Cohort D: Progressive disease |
| Cohort E: Hematological neoplasmsAny 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. | Genetic | Cohort E: Hematological neoplasms |
| Cohort F: ToxicityIn 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) | Genetic | Cohort F: Toxicity |
Primary outcome
Percentage of patients in each cohort that will obtain a full "core" omic characterization.
Time frame: 2 months
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
1 secondary outcome
Percentage of patients with complete clinical data collection over the expected follow-up time and with successful biobanking.
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luca Mazzarella principal investigator
European Institute of Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer and Lung Cancer, run by European Institute of Oncology at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Luca Mazzarella (+390294375111, luca.mazzarella@ieo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients in each cohort that will obtain a full "core" omic characterization. (time frame: 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2024.