临床试验/NCT04591431

NCT04591431进行中（未招募）2 期

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

Fondazione per la Medicina Personalizzata37 个研究点分布在 1 个国家目标入组 400 人开始时间: 2020年10月7日最近更新: 2023年10月3日

适应症

干预措施

试验速览

阶段: 2 期
状态: 进行中（未招募）
发起方: Fondazione per la Medicina Personalizzata
入组人数: 400
试验地点: 37
主要终点: OVERALL RESPONSE RATE (ORR)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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:

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•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.

排除标准

•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

研究组 & 干预措施

Tailored Therapy

Experimental

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)

干预措施: Erlotinib (Drug)

Tailored Therapy

Experimental

干预措施: Trastuzumab (Drug)

Tailored Therapy

Experimental

干预措施: Trastuzumab emtansine (Drug)

Tailored Therapy

Experimental

干预措施: Pertuzumab (Drug)

Tailored Therapy

Experimental

干预措施: Lapatinib (Drug)

Tailored Therapy

Experimental

干预措施: Everolimus (Drug)

Tailored Therapy

Experimental

干预措施: Vemurafenib (Drug)

Tailored Therapy

Experimental

干预措施: Cobimetinib (Drug)

Tailored Therapy

Experimental

干预措施: Alectinib (Drug)

Tailored Therapy

Experimental

干预措施: Brigatinib (Drug)

Tailored Therapy

Experimental

干预措施: Palbociclib (Drug)

Tailored Therapy

Experimental

干预措施: Ponatinib (Drug)

Tailored Therapy

Experimental

干预措施: Vismogedib (Drug)

Tailored Therapy

Experimental

干预措施: Itacitinib (Drug)

Tailored Therapy

Experimental

干预措施: Ipatasertib (Drug)

Tailored Therapy

Experimental

干预措施: Entrectinib (Drug)

Tailored Therapy

Experimental

干预措施: Atezolizumab (Drug)

Tailored Therapy

Experimental

干预措施: Nivolumab (Drug)

Tailored Therapy

Experimental

干预措施: Ipilimumab (Drug)

Tailored Therapy

Experimental

干预措施: Pemigatinib (Drug)

Tailored Therapy

Experimental

干预措施: Pralsetinib (Drug)

Tailored Therapy

Experimental

干预措施: Selpercatinib (Drug)

Tailored Therapy

Experimental

干预措施: Talazoparib (Drug)

Tailored Therapy

Experimental

干预措施: Tepotinib (Drug)

Tailored Therapy

Experimental

干预措施: Alpelisib (Drug)

Standard of Care

Active Comparator

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.

干预措施: Oncology Drugs (Drug)

结局指标

主要结局

OVERALL RESPONSE RATE (ORR)

时间窗: 42 months

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.

次要结局

Progression Free Survival (PFS) of SoC vs TT(42 months)
Time to Next Treatment (TTNT) of SoC vs TT(42 months)
Time to Treatment Failure (TTF) 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)
The safety profile between the two treatment arms of SoC vs TT(42 months)
Overall survival (OS)(42 months)

研究者

发起方

Fondazione per la Medicina Personalizzata

申办方类型

Other

责任方

Sponsor

研究点 (37)

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