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The Rome Trial From Histology to Target: the Road to Personalize Target Therapy and Immunotherapy (ROME)

Primary Purpose

Breast Cancer, Gastrointestinal Cancer, Non Small Cell Lung Cancer

Status
Active
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Erlotinib
Trastuzumab
Trastuzumab emtansine
Pertuzumab
Lapatinib
Everolimus
Vemurafenib
Cobimetinib
Alectinib
Brigatinib
Palbociclib
Ponatinib
Vismogedib
Itacitinib
Ipatasertib
Entrectinib
Atezolizumab
Nivolumab
Ipilimumab
Pemigatinib
Oncology Drugs
Pralsetinib
Selpercatinib
Talazoparib
Tepotinib
Alpelisib
Sponsored by
Fondazione per la Medicina Personalizzata
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age ≥ 18 at time of signing Informed Consent Form
  2. Patients able and willing to provide a written informed consent to participate to the study
  3. Patients with recurrent/metastatic breast, gastrointestinal cancer,non small cell lung cancer or others
  4. Patients not treatable with potentially curative surgery ot other loco-regional treatments.
  5. Patients should have been completed at least 1 line of treatment for breast cancer, gastro-intestinal, non small cell lung cancer or other cancer
  6. ECOG performance status from 0 to 1
  7. Molecular target not actionable with approved drugs identified during screening by profiling with Foundation One on biopsy and Foundation ACT on blood
  8. Biopsiable disease (tumor biopsy mandatory for tumor profiling). The biopsy must be performed during the screening period, when patients complete the conventional therapy for their recurrent/metastatic cancer. Historical samples will be considered for the study if collected within 3 months before the ICF signature of the patient. Samples older than 3 months, with a maximum timeframe of 6 months, will be considered upon clinical judgement of the Investigator.
  9. Measurable disease, eligible to standard treatment. Patients must have measurable or evaluable disease defined, per RECIST 1.1 or irCS (immune related Response Criteria), as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral computed tomography (CT) scan, Magnetic Resonance Imaging (MRI), or a subcutaneous or superficial lesion that can be measured with calipers by clinical exam. For lymph nodes, the short axis must be ≥15 mm. Patients who have assessable disease by physical or radiographic examination but do not fully meet the above definitions of measurable disease (but still remains measurable) are eligible and will be considered to have evaluable disease. Patient's whose disease cannot be objectively measured by physical or radiographic examination (e.g., elevated serum tumor marker only) are NOT eligible. PET scan could be performed, if clinically indicated. For PET response evaluation PERCIST criteria will be applied.
  10. Adequate renal function defined by a serum creatinine <1.5xUNL (upper normal limit).
  11. Adequate liver function test defined by SGOT & SGPT <3xUNL (5xUNL in case of liver metastases), and bilirubin level <1.5xUNL
  12. Adequate bone marrow function defined by platelets >100,000/mm3, hemoglobin >10 g/dL, and neutrophils >1,000/mm3
  13. For female of child-bearing potential and for all women < 1 years after the onset of menopause: a negative pregnancy test <72 hours before starting study treatment is required. If sexually active, female of childbearing potential must use "highly effective" methods of contraception for the study duration. Contraception should continue after the last treatment for 3 months or for longer periods according to what reported in the Appendix 1 of the Protocol
  14. For male of reproductive potential: any sexually active male patient must use a condom while on study treatment. Contraception should continue after the last treatment for 3 months or for longer periods according to what reported in the Appendix 1 of the Protocol.

Exclusion Criteria:

  1. Patients who have only bone and/or brain metastases
  2. Patients treated with more than 2 lines for breast cancer, gastro-intestinal, non small cell lung cancer and other cancer
  3. Patients whose brain metastases have not been monitored for >2 months
  4. Patients with well-established actionable targets for which approved and marketed targeted drugs are available (i.e. lung cancer with EGFR mutation, or ALK translocation, B-RAF mutant melanoma, GIST with KIT mutations or breast cancer with HER2 amplification)
  5. Patient participating in another clinical trial with an experimental drug
  6. Anticoagulation with anti-vitamin K (Low Molecular Weight Heparin [LMWH] is allowed)
  7. Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, including uncontrolled diabetes, cardiac disease, uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within one year, chronic liver or renal disease, active gastrointestinal tract ulceration, severely impaired lung function
  8. Pregnant and/or breastfeeding women
  9. Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  10. HIV, HBV, or HCV infection as per specific test performed at the screening visit or known as per Medical History
  11. Patients with documented contraindication to any of the IMPs that will be used for the study, as reported in the respective SmPcs/IBs and in Appendix 2
  12. Patients treated with the following drugs, because of the risk of immunosuppression: Chronic or high-dose oral corticosteroid therapy, TNF-inhibitors and Anti-T cell antibodies

Sites / Locations

  • OSPEDALI RIUNITI di ANCONA
  • Centro Riferimento Oncologico
  • Irccs Oncologico Istituto Tumori Giovanni Paolo Ii - Bari
  • Asst Papa Giovanni Xxiii
  • Ospedale Bellaria
  • Ospedale di Carpi
  • Arnas Garibaldi- Nuovo Ospedale Garibaldi - Nesima
  • A.O. Mater Domini Catanzaro
  • Azienda Ospedaliero-Universitaria Di Ferrara
  • E.O. Ospedali Galliera
  • Ospedale Policlinico San Martino
  • Ospedale Della Misericordia
  • I.R.S.T. Srl Irccs
  • Ao Papardo
  • Istituto Europeo Di Oncologia
  • Istituto Nazionale Tumori Di Napoli Irccs Pascale
  • Ospedale Classificato Sacro Cuore - Don Calabria
  • I.R.C.C.S. Istituto Oncologico Veneto
  • Az.Osp.Univ.P.Giaccone
  • Azienda Ospedaliera Di Perugia
  • Casa Di Cura Privata Osp. P. Pederzoli
  • Azienda Usl Di Piacenza
  • Azienda Ospedaliero-Universitaria Pisana
  • Nuovo Ospedale Di Prato - S. Stefano
  • Ospedale "Santa Maria Delle Croci"
  • Arcispedale Santa Maria Nuova Di Reggio Emilia
  • Az. Osp. Uni. Policlinico Umberto I
  • Azienda Ospedaliera Sant'Andrea
  • Istituti Fisioterapici Ospitalieri- Ifo - Istituto Regina Elena
  • Ospedale Fatebenefratelli
  • Policl. Univ. Campus Bio Medico
  • Casa Sollievo della Sofferenza - Opera Padre Pio
  • Azienda Ospedaliera 'S. Maria' - Terni
  • AO Ordine Mauriziano
  • Humanitas Gradenigo
  • IRCCS Candiolo
  • Complesso Ospedaliero Di Belcolle- Ospedale Di Belcolle

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Tailored Therapy

Standard of Care

Arm Description

Experimental (TT) Patients will be treated with target therapy and/or immunotherapy according to their genomic profile evidenced by Foundation One test and independently from their type of cancer with one or more drugs of the following list (administered according to the SmPCs or IBs if under development): TARGET THERAPY: ERLOTINIB (EGFR mutation) TRASTUZUMAB, PERTUZUMAB, TDM1, LAPATINIB (ERBB2 amplifications/mut) EVEROLIMUS (mTOR mutations, AKT mut) VEMURAFENIB, COBIMETINIB (BRAFV600E mutations) ALECTINIB, BRIGATINIB (ALK, RET) PALBOCICLIB (CDK4/6, CDKN2A/p16) PONATINIB (Bcr-abl) VISMODEGIB (SMO/PTCH1) ITACITINIB (JAK mutation) INCB054828 (FGFR1/2/3) IPATASERTIB (PI3K, AKT, PTEN) ENTRECTINIB (NTRK1/2/3 -TRK fusion proteins-, ROS1) ALPELISIB (PI3K, AKT) TEPOTINIB (MET amplification/exon14 skipping mutations) PRALSETINIB (RET) TALAZOPARIB (BRCA1/2, ATM, other HRD status) SELPERCATINIB (RET) IMMUNOTHERAPY: ATEZOLIZUMAB, NIVOLUMAB, IPILIMUMAB (MSI, HIGH TUMOR MUTATIONAL BURDEN, OTHER)

Patients will be treated according the current version of the AIOM (Italian Association of Medical Oncology) guidelines for their type of cancer. As an example, patients could be treated with standard chemotherapy and/or targeted therapy according to the histological results.

Outcomes

Primary Outcome Measures

OVERALL RESPONSE RATE (ORR)
Evaluation of the ORR of the Treatment at choice of physicians, according to Standard of Care (SoC) or of the Tailored Treatment (TT). The ORR will be constructed according to the specific design of the study, therefore including also the Rescue Therapy Phase data. This means that the ORR will take into account 3 evaluations: on the original final population ( i.e 384 patients divided into the 4 groups of type of cancer) on the TT patients, which will include the original randomized TT patients and the patients switched from the standard of care therapy (SoC therapy) to the TT Therapy, this latter within the Rescue Therapy Phase (patients switching upon the first documented progression) on the population composed by the original TT patients, the original SoC patients and the switched TT patients. This means that the total population analyzed will include the original 384 population data (as per randomization) and the additional switched TT patients.

Secondary Outcome Measures

Progression Free Survival (PFS) of SoC vs TT
Time to Treatment Failure (TTF) of SoC vs TT
Time to Next Treatment (TTNT) of SoC vs TT
Concordance between molecular profile on tumor tissue and ctDNA
Will be evaluated the concordance between Foundation One results on tumor tissue and blood sample. Overlapping mutational results will be considered as "concordant" otherwise will be considered as "discordant". Both qualitative and quantitative differences in mutational status will be considered.
QoLs included in the two arms of the study of SoC vs TT
The QoL score will be measured in the two arms of the study (SoC and TT), using the EORTC QLQ-C30, a validated questionnaire designed to assess different aspects of health and quality of life for cancer patients. Data from the two Quality of Life (QoL) questionnaires will be descriptively analyzed.
The safety profile between the two treatment arms of SoC vs TT
Percentage of Participants with Adverse Events (AEs) or Serious AEs (SAEs).
Overall survival (OS)
● Overall survival (OS) is defined as the time from randomization to death from any cause. Data for patients with no record of death will be censored at the last date they were known to be alive. The analysis of OS will follow the same methodology as the primary endpoint.

Full Information

First Posted
September 18, 2020
Last Updated
October 2, 2023
Sponsor
Fondazione per la Medicina Personalizzata
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1. Study Identification

Unique Protocol Identification Number
NCT04591431
Brief Title
The Rome Trial From Histology to Target: the Road to Personalize Target Therapy and Immunotherapy
Acronym
ROME
Official Title
The Rome Trial From Histology to Target: the Road to Personalize Target Therapy and Immunotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 7, 2020 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fondazione per la Medicina Personalizzata

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
This is a randomized, prospective, multicenter, Proof of Concept, Phase II clinical trial Study. The main objective of the study is to evaluate the efficacy (meant as overall response rate ORR) of TT (targeted Therapy) vs SoC (standard of Care) in patients with progressive disease (recurrent and/or metastatic) of breast cancer, metastatic gastro-intestinal tumors, non small cell lung cancer (NSCLC) or others. Patients should have completed at least 1 line of treatment and no more than 2 as defined by the current version of the AIOM (Italian Association of Medical Oncology) guidelines. Patients are included if surgery is contraindicated.
Detailed Description
Personalizing cancer medicine depends on the implementation of personalized diagnostics and therapeutics. Detailed genomic and gene expression signatures screening are likely to play a central role in this. Personalized Medicine has been widely depicted as a striking innovation, that is able to reform the standard approach to disease management, replacing the one-size-fits-all scheme of medicine with a single-patient-sized medical intervention. Personalized medicine promoters usually highlight its potential to combine a more effective health-care with costs containment, according to the following rules: monitoring of disease risks and more effective prevention; early intervention; selection of optimal therapy; reduction of trial-and-error prescribing and reduction of adverse drug reactions; exclusion of unnecessary drugs; therapeutic drug monitoring and disease progression/remission monitoring; increased patient compliance with therapy. In spite of expectations, many unsolved practical issues, from technical and scientific to ethical, legal and economic topics, are slowing down the translation of personalized medicine principles into medical practice. Furthermore, wide adoption of personalized strategies also has to deal with the peculiar rules, policy and reimbursement system of each country. Application of Personalized Medicine in the real world seems entangled by the unmet need to develop evidence-based guidelines. The benefits of personalized medicine in routine clinical practice have firstly emerged in oncology. The power of precision medicine in the field of anticancer therapy resides in the possibility to characterize the genomic profile of both the disease (eg somatic mutations in the tumor tissue or blood sample) and the patient (eg the germinal genomic profile). The first piece of information allows stratification of patients in responder and non-responder to specific drugs, improving efficacy and avoiding wasting of expensive medications as biological drugs. Personalized medicine for cancer can be classified in: targeted therapy (which bloks the growth of cancer cells by interfering with specific molecular targets of cancer cells) or immunotherapy (which use the body'immune system to fight cancer cells by stimulating the immune system) Targeted therapy belongs to Personalized Medicine approach and the study of genetic mutations on tumor tissue or blood sample (CTC or cfDNA ) are changing the scenario of the treatment approach of cancer patients. In clinical practice, the use of target therapies driven by mutation's assessment has radically changed the survival of patients affected by breast cancer, NSCLC, melanoma, colo-rectal cancer, while the clinical application of specific gene expression signatures is driving the choice of the best adjuvant strategy in early breast cancer. Despite the efficacy of such approach its use is restricted to a relatively small fraction of patients and the evaluation of mutation is conditioned by the primary site of the cancer, i.e. by the tumor histology. The current biological understanding leads to hypothesize that the cancer behavior is highly dependent from the underlying driver genetic alterations independently from the histology. It's widely demonstrated that such molecular alterations are detected regardless of the histology, and this has already modified the treatment approach of some cancers. Furthermore, several studies have demonstrated the efficacy of the choice of treatment according to genomic evaluation regardless of its histology with acceptable cost-effectiveness profile. In the context of precision medicine the Immuno-oncology is becoming Precision Immuno-oncology and the efforts of science are directed towards the identification of predictive biomarkers of response to immune checkpoint inhibitors. Promising biomarkers are Microsatellite Instability (MSI) and the tumour mutational load (TMB). In particular TMB is a quantitative biomarker that reflects the total number of mutations carried by tumor cells. TMB is well-known to reflect neoantigens burden potentially recognized by the immune system. This has been shown to correlate with better anti-PD-1 response in particular for both pembrolizumab and nivolumab combined with ipilimumab . The same findings were demonstrated in the OAK study considering peripheral blood mutational load and response to atezolizumab. High tumor mutation burden (defined as tumors that have high ≥10 mutations/megabase, mut/mb) allows to identify 45% of patients who can benefit from immunotherapy regardless of PD-L1 expression. So, ever keeping in mind that although many evidences are available, the relationship between histology and genomic alterations is still under definition, as well as the relationship between the latter and gene expression. The aim of the present investigation is to combine all of the information available to drive the therapy selection according to the genomic alteration profile. Therefore, the main objective of our study is to evaluate the efficacy of therapy according to genomic profile (TT - Tailored Treatment) versus Standard of Care (SoC). A molecular profile of the cancer will be evaluated on tumor tissue biopsy (using the Foundation One (with updated gene panel 324 gene reflecting CDx) at the time of patient inclusion in the trial and on circulating DNA fragments (i.e. using FoundationOne Liquid test) at the time of patient inclusion in the trial and at progression of disease. This study is a Phase II, randomized, multicenter, Proof of Concept, clinical trial. Patients with progressive disease (recurrent and/or metastatic) of breast cancer, metastatic gastro-intestinal tumors, non small cell lung cancer (NSCLC) or others will be included. Patients should have completed at least 1 line of treatment and no more than 2 as defined by the current version of the AIOM guidelines. Patients are included if surgery is contraindicated. Patients could have received targeted therapy for metastatic disease. A molecular profile of the cancer will be evaluated on tumor tissue biopsy and on ctDNA of around 1280 patients at patient inclusion. After FO evaluations patients with actionable mutations, not previous identified with other methods, for which approved drugs according to histotype are available, will be excluded. Once identified molecular abnormalities (not only those that are disease-specific), that can be modulated with target or immunotherapeutic intervention available within the present study, patients will be randomized to receive: ARM A: Therapy at choice of physician, according to Standard of Care (SoC) ARM B: Tailored treatment according to genomic profile (Tailored Treatment, TT) The Molecular Tumor Board (MTB) will define the target therapy and immunotherapy while standard treatment will be decided by study physicians. Patients should remain in the treatment phase of the study until investigator assesses radiographic or clinical progressive disease, unmanageable toxicity, or study termination. Tumor assessments will be conducted every 12 weeks from the date of randomization until any of the above events occurs. Delays in treatment administration will not impact the timing of the tumor assessments. If a tumor assessment must be performed early/late, subsequent assessments will be conducted according to the original schedule of every 12 weeks from the date of randomization. At the time of the first progression of disease: blood sample will be collected to evaluate the molecular profile of the cancer on circulating DNA fragments (i.e. using FoundationOne Liquid test) Study treatment (SoC or TT) will be interrupted waiting for the evaluations for the Rescue/Switched Phase Tumor assessments must be conducted until progressive disease (PD for RECIST 1.1 or iCPD for iRECIST if clinically indicated), even if treatment has been discontinued due to investigator-determined PD or unacceptable toxicity. After discontinuation of study treatment for reason different from progressive disease and withdrawal of consent, tumor assessments will continue until progression. In addition, patients will be followed for survival until death, loss to follow-up, withdrawal of consent, or study termination.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Gastrointestinal Cancer, Non Small Cell Lung Cancer, Other Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized, prospective, multicenter, Proof of Concept, Phase II clinical trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
400 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tailored Therapy
Arm Type
Experimental
Arm Description
Experimental (TT) Patients will be treated with target therapy and/or immunotherapy according to their genomic profile evidenced by Foundation One test and independently from their type of cancer with one or more drugs of the following list (administered according to the SmPCs or IBs if under development): TARGET THERAPY: ERLOTINIB (EGFR mutation) TRASTUZUMAB, PERTUZUMAB, TDM1, LAPATINIB (ERBB2 amplifications/mut) EVEROLIMUS (mTOR mutations, AKT mut) VEMURAFENIB, COBIMETINIB (BRAFV600E mutations) ALECTINIB, BRIGATINIB (ALK, RET) PALBOCICLIB (CDK4/6, CDKN2A/p16) PONATINIB (Bcr-abl) VISMODEGIB (SMO/PTCH1) ITACITINIB (JAK mutation) INCB054828 (FGFR1/2/3) IPATASERTIB (PI3K, AKT, PTEN) ENTRECTINIB (NTRK1/2/3 -TRK fusion proteins-, ROS1) ALPELISIB (PI3K, AKT) TEPOTINIB (MET amplification/exon14 skipping mutations) PRALSETINIB (RET) TALAZOPARIB (BRCA1/2, ATM, other HRD status) SELPERCATINIB (RET) IMMUNOTHERAPY: ATEZOLIZUMAB, NIVOLUMAB, IPILIMUMAB (MSI, HIGH TUMOR MUTATIONAL BURDEN, OTHER)
Arm Title
Standard of Care
Arm Type
Active Comparator
Arm Description
Patients will be treated according the current version of the AIOM (Italian Association of Medical Oncology) guidelines for their type of cancer. As an example, patients could be treated with standard chemotherapy and/or targeted therapy according to the histological results.
Intervention Type
Drug
Intervention Name(s)
Erlotinib
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Trastuzumab emtansine
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Pertuzumab
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Lapatinib
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Everolimus
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Vemurafenib
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Cobimetinib
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Alectinib
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Brigatinib
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Palbociclib
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Ponatinib
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Vismogedib
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Itacitinib
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Ipatasertib
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Entrectinib
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Ipilimumab
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Pemigatinib
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Oncology Drugs
Intervention Description
Standard of Care Arm
Intervention Type
Drug
Intervention Name(s)
Pralsetinib
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Selpercatinib
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Talazoparib
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Tepotinib
Intervention Description
TT arm
Intervention Type
Drug
Intervention Name(s)
Alpelisib
Intervention Description
TT arm
Primary Outcome Measure Information:
Title
OVERALL RESPONSE RATE (ORR)
Description
Evaluation of the ORR of the Treatment at choice of physicians, according to Standard of Care (SoC) or of the Tailored Treatment (TT). The ORR will be constructed according to the specific design of the study, therefore including also the Rescue Therapy Phase data. This means that the ORR will take into account 3 evaluations: on the original final population ( i.e 384 patients divided into the 4 groups of type of cancer) on the TT patients, which will include the original randomized TT patients and the patients switched from the standard of care therapy (SoC therapy) to the TT Therapy, this latter within the Rescue Therapy Phase (patients switching upon the first documented progression) on the population composed by the original TT patients, the original SoC patients and the switched TT patients. This means that the total population analyzed will include the original 384 population data (as per randomization) and the additional switched TT patients.
Time Frame
42 months
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS) of SoC vs TT
Time Frame
42 months
Title
Time to Treatment Failure (TTF) of SoC vs TT
Time Frame
42 months
Title
Time to Next Treatment (TTNT) of SoC vs TT
Time Frame
42 months
Title
Concordance between molecular profile on tumor tissue and ctDNA
Description
Will be evaluated the concordance between Foundation One results on tumor tissue and blood sample. Overlapping mutational results will be considered as "concordant" otherwise will be considered as "discordant". Both qualitative and quantitative differences in mutational status will be considered.
Time Frame
42 months
Title
QoLs included in the two arms of the study of SoC vs TT
Description
The QoL score will be measured in the two arms of the study (SoC and TT), using the EORTC QLQ-C30, a validated questionnaire designed to assess different aspects of health and quality of life for cancer patients. Data from the two Quality of Life (QoL) questionnaires will be descriptively analyzed.
Time Frame
42 months
Title
The safety profile between the two treatment arms of SoC vs TT
Description
Percentage of Participants with Adverse Events (AEs) or Serious AEs (SAEs).
Time Frame
42 months
Title
Overall survival (OS)
Description
● Overall survival (OS) is defined as the time from randomization to death from any cause. Data for patients with no record of death will be censored at the last date they were known to be alive. The analysis of OS will follow the same methodology as the primary endpoint.
Time Frame
42 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 at time of signing Informed Consent Form Patients able and willing to provide a written informed consent to participate to the study Patients with recurrent/metastatic breast, gastrointestinal cancer,non small cell lung cancer or others Patients not treatable with potentially curative surgery ot other loco-regional treatments. Patients should have been completed at least or failed the first line of treatment for breast cancer, gastro-intestinal, non small cell lung cancer or other cancer ECOG performance status from 0 to 1 Molecular target not actionable with approved drugs identified during screening by profiling with FoundationOne CDX on biopsy and FoundationOne Liquid CDx on blood Biopsiable disease (tumor biopsy mandatory for tumor profiling). The biopsy must be performed during the screening period, when patients complete the conventional therapy for their recurrent/metastatic cancer. Historical samples will be considered for the study if collected within 3 months before the ICF signature of the patient. Samples older than 3 months, with a maximum timeframe of 6 months, and collected before progression of disease after the last treatment administered will be considered upon clinical judgement of the Investigator, after confirmation by the coordinating site or MTB. Samples obtained from a biospy of a metastatic lesion in progression after the last treatment administered represent the optimal tissue sample for genomic testing. Patients with glioblastomas and high grade malignant gliomas can be enrolled with the historical tissue samples. Measurable disease, eligible to standard treatment. Patients must have measurable or evaluable disease defined, per RECIST 1.1 or irCS (immune related Response Criteria), as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral computed tomography (CT) scan, Magnetic Resonance Imaging (MRI), or a subcutaneous or superficial lesion that can be measured with calipers by clinical exam. For lymph nodes, the short axis must be ≥15 mm. Patients who have assessable disease by physical or radiographic examination but do not fully meet the above definitions of measurable disease (but still remains measurable) are eligible and will be considered to have evaluable disease. Patient's whose disease cannot be objectively measured by physical or radiographic examination (e.g., elevated serum tumor marker only) are NOT eligible. PET scan could be performed, if clinically indicated. For PET response evaluation PERCIST criteria will be applied. Adequate renal function defined by a serum creatinine <1.5xUNL (upper normal limit). Adequate liver function test defined by SGOT & SGPT <3xUNL (5xUNL in case of liver metastases), and bilirubin level <1.5xUNL Adequate bone marrow function defined by platelets >100,000/mm3, hemoglobin >10 g/dL, and neutrophils >1,000/mm3 For female of child-bearing potential and for all women < 1 years after the onset of menopause: a negative pregnancy test <72 hours before starting study treatment is required. If sexually active, female of childbearing potential must use "highly effective" methods of contraception for the study duration. Contraception should continue after the last treatment for 3 months or for longer periods according to what reported in the Appendix 1 of the Protocol For male of reproductive potential: any sexually active male patient must use a condom while on study treatment. Contraception should continue after the last treatment for 3 months or for longer periods according to what reported in the Appendix 1 of the Protocol. Exclusion Criteria: Patients who have only bone and/or brain metastases Patients treated with more than 2 lines for breast cancer, gastro-intestinal, non small cell lung cancer and other cancer Patients with uncontrolled disease (untreated and/or sintomatic) and patients whose brain metastases have not been monitored for >2 months Patients with well-established actionable targets for which approved and marketed targeted drugs are available (i.e. lung cancer with EGFR mutation, or ALK translocation, B-RAF mutant melanoma, GIST with KIT mutations or breast cancer with HER2 amplification) Patient participating in another clinical trial with an experimental drug Anticoagulation with anti-vitamin K (Low Molecular Weight Heparin [LMWH] is allowed) Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, including uncontrolled diabetes, cardiac disease, uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within one year, chronic liver or renal disease, active gastrointestinal tract ulceration, severely impaired lung function Pregnant and/or breastfeeding women Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule HIV, HBV, or HCV infection as per specific test performed at the screening visit or known as per Medical History Patients with documented contraindication to any of the IMPs that will be used for the study, as reported in the respective SmPcs/IBs and in Appendix 2 Patients treated with the following drugs, because of the risk of immunosuppression: Chronic or high-dose oral corticosteroid therapy, TNF-inhibitors and Anti-T cell antibodies
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paolo Marchetti
Organizational Affiliation
Fondazione per la Medicina Personalizzata
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Andrea Botticelli
Organizational Affiliation
Università degli Studi di Roma Sapienza
Official's Role
Principal Investigator
Facility Information:
Facility Name
OSPEDALI RIUNITI di ANCONA
City
Ancona
Country
Italy
Facility Name
Centro Riferimento Oncologico
City
Aviano
Country
Italy
Facility Name
Irccs Oncologico Istituto Tumori Giovanni Paolo Ii - Bari
City
Bari
Country
Italy
Facility Name
Asst Papa Giovanni Xxiii
City
Bergamo
Country
Italy
Facility Name
Ospedale Bellaria
City
Bologna
Country
Italy
Facility Name
Ospedale di Carpi
City
Carpi
Country
Italy
Facility Name
Arnas Garibaldi- Nuovo Ospedale Garibaldi - Nesima
City
Catania
Country
Italy
Facility Name
A.O. Mater Domini Catanzaro
City
Catanzaro
Country
Italy
Facility Name
Azienda Ospedaliero-Universitaria Di Ferrara
City
Ferrara
Country
Italy
Facility Name
E.O. Ospedali Galliera
City
Genova
Country
Italy
Facility Name
Ospedale Policlinico San Martino
City
Genova
Country
Italy
Facility Name
Ospedale Della Misericordia
City
Grosseto
Country
Italy
Facility Name
I.R.S.T. Srl Irccs
City
Meldola
Country
Italy
Facility Name
Ao Papardo
City
Messina
Country
Italy
Facility Name
Istituto Europeo Di Oncologia
City
Milano
Country
Italy
Facility Name
Istituto Nazionale Tumori Di Napoli Irccs Pascale
City
Napoli
Country
Italy
Facility Name
Ospedale Classificato Sacro Cuore - Don Calabria
City
Negrar
Country
Italy
Facility Name
I.R.C.C.S. Istituto Oncologico Veneto
City
Padova
Country
Italy
Facility Name
Az.Osp.Univ.P.Giaccone
City
Palermo
Country
Italy
Facility Name
Azienda Ospedaliera Di Perugia
City
Perugia
Country
Italy
Facility Name
Casa Di Cura Privata Osp. P. Pederzoli
City
Peschiera Del Garda
Country
Italy
Facility Name
Azienda Usl Di Piacenza
City
Piacenza
Country
Italy
Facility Name
Azienda Ospedaliero-Universitaria Pisana
City
Pisa
Country
Italy
Facility Name
Nuovo Ospedale Di Prato - S. Stefano
City
Prato
Country
Italy
Facility Name
Ospedale "Santa Maria Delle Croci"
City
Ravenna
Country
Italy
Facility Name
Arcispedale Santa Maria Nuova Di Reggio Emilia
City
Reggio Emilia
Country
Italy
Facility Name
Az. Osp. Uni. Policlinico Umberto I
City
Roma
Country
Italy
Facility Name
Azienda Ospedaliera Sant'Andrea
City
Roma
Country
Italy
Facility Name
Istituti Fisioterapici Ospitalieri- Ifo - Istituto Regina Elena
City
Roma
Country
Italy
Facility Name
Ospedale Fatebenefratelli
City
Roma
Country
Italy
Facility Name
Policl. Univ. Campus Bio Medico
City
Roma
Country
Italy
Facility Name
Casa Sollievo della Sofferenza - Opera Padre Pio
City
San Giovanni Rotondo
Country
Italy
Facility Name
Azienda Ospedaliera 'S. Maria' - Terni
City
Terni
Country
Italy
Facility Name
AO Ordine Mauriziano
City
Torino
Country
Italy
Facility Name
Humanitas Gradenigo
City
Torino
Country
Italy
Facility Name
IRCCS Candiolo
City
Torino
Country
Italy
Facility Name
Complesso Ospedaliero Di Belcolle- Ospedale Di Belcolle
City
Viterbo
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

The Rome Trial From Histology to Target: the Road to Personalize Target Therapy and Immunotherapy

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