The Rome Trial From Histology to Target: the Road to Personalize Target Therapy and Immunotherapy
ROME
2 other identifiers
interventional
400
1 country
37
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 breast-cancer
Started Oct 2020
Typical duration for phase_2 breast-cancer
37 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 18, 2020
CompletedStudy Start
First participant enrolled
October 7, 2020
CompletedFirst Posted
Study publicly available on registry
October 19, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2025
CompletedOctober 3, 2023
October 1, 2023
4.2 years
September 18, 2020
October 2, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
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.
42 months
Secondary Outcomes (7)
Progression Free Survival (PFS) of SoC vs TT
42 months
Time to Treatment Failure (TTF) of SoC vs TT
42 months
Time to Next Treatment (TTNT) of SoC vs TT
42 months
Concordance between molecular profile on tumor tissue and ctDNA
42 months
QoLs included in the two arms of the study of SoC vs TT
42 months
- +2 more secondary outcomes
Study Arms (2)
Tailored Therapy
EXPERIMENTALExperimental (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)
Standard of Care
ACTIVE COMPARATORPatients 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.
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (37)
OSPEDALI RIUNITI di ANCONA
Ancona, Italy
Centro Riferimento Oncologico
Aviano, Italy
Irccs Oncologico Istituto Tumori Giovanni Paolo Ii - Bari
Bari, Italy
Asst Papa Giovanni Xxiii
Bergamo, Italy
Ospedale Bellaria
Bologna, Italy
Ospedale di Carpi
Carpi, Italy
Arnas Garibaldi- Nuovo Ospedale Garibaldi - Nesima
Catania, Italy
A.O. Mater Domini Catanzaro
Catanzaro, Italy
Azienda Ospedaliero-Universitaria Di Ferrara
Ferrara, Italy
E.O. Ospedali Galliera
Genova, Italy
Ospedale Policlinico San Martino
Genova, Italy
Ospedale Della Misericordia
Grosseto, Italy
I.R.S.T. Srl Irccs
Meldola, Italy
Ao Papardo
Messina, Italy
Istituto Europeo Di Oncologia
Milan, Italy
Istituto Nazionale Tumori Di Napoli Irccs Pascale
Napoli, Italy
Ospedale Classificato Sacro Cuore - Don Calabria
Negrar, Italy
I.R.C.C.S. Istituto Oncologico Veneto
Padua, Italy
Az.Osp.Univ.P.Giaccone
Palermo, Italy
Azienda Ospedaliera Di Perugia
Perugia, Italy
Casa Di Cura Privata Osp. P. Pederzoli
Peschiera del Garda, Italy
Azienda Usl Di Piacenza
Piacenza, Italy
Azienda Ospedaliero-Universitaria Pisana
Pisa, Italy
Nuovo Ospedale Di Prato - S. Stefano
Prato, Italy
Ospedale "Santa Maria Delle Croci"
Ravenna, Italy
Arcispedale Santa Maria Nuova Di Reggio Emilia
Reggio Emilia, Italy
Az. Osp. Uni. Policlinico Umberto I
Roma, Italy
Azienda Ospedaliera Sant'Andrea
Roma, Italy
Istituti Fisioterapici Ospitalieri- Ifo - Istituto Regina Elena
Roma, Italy
Ospedale Fatebenefratelli
Roma, Italy
Policl. Univ. Campus Bio Medico
Roma, Italy
Casa Sollievo della Sofferenza - Opera Padre Pio
San Giovanni Rotondo, Italy
Azienda Ospedaliera 'S. Maria' - Terni
Terni, Italy
AO Ordine Mauriziano
Torino, Italy
Humanitas Gradenigo
Torino, Italy
IRCCS Candiolo
Torino, Italy
Complesso Ospedaliero Di Belcolle- Ospedale Di Belcolle
Viterbo, Italy
Related Publications (1)
Marchetti P, Curigliano G, Biffoni M, Lonardi S, Scagnoli S, Fornaro L, Guarneri V, De Giorgi U, Ascierto PA, Blandino G, D'Amati G, Aglietta M, Cremolini C, Conte P, Crimini E, Ceracchi M, Pisegna S, Verkhovskaia S, Bordonaro R, Bracarda S, Butturini G, Del Mastro L, DeCensi A, Fabbri A, Fenocchio E, Gori S, Metro G, Pessino A, Pozzessere D, Puglisi F, Tamberi S, Zambelli A, Marino D, Capoluongo E, Cappuzzo F, Cerbelli B, Giannini G, Malapelle U, Mazzuca F, Nuti M, Pruneri G, Simmaco M, Strigari L, Tonini G, Martini N, Botticelli A; ROME trial investigators consortia. Genomically matched therapy in advanced solid tumors: the randomized phase 2 ROME trial. Nat Med. 2025 Oct;31(10):3514-3523. doi: 10.1038/s41591-025-03918-x. Epub 2025 Sep 29.
PMID: 41023484DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Paolo Marchetti
Fondazione per la Medicina Personalizzata
- PRINCIPAL INVESTIGATOR
Andrea Botticelli
Università degli Studi di Roma Sapienza
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 18, 2020
First Posted
October 19, 2020
Study Start
October 7, 2020
Primary Completion
December 1, 2024
Study Completion
June 1, 2025
Last Updated
October 3, 2023
Record last verified: 2023-10
Data Sharing
- IPD Sharing
- Will not share