Precision Medicine Trial Based on Molecular Matching Therapy for Patients With Standard Treatment Exhaustion
Phase 2
Recruiting
- Conditions
- Interventions
- Drug: Target GeneDrug: Olaparib tabletDrug: Temozolomide capsuleDrug: AnlotinibDrug: Trametinib tabletDrug: DabrafenibDrug: Vebreltinib Enteric CapsulesDrug: Alpelisib PillDrug: Sacituzumab Govitecan-Hziy 180 MGDrug: Lenvatinib CapsulesDrug: Pazopanib PillDrug: Palbociclib PillDrug: ChidamideDrug: PD-1/PD-L1/PD-1&CTLA4 inhibitor
- Registration Number
- NCT06739395
- Lead Sponsor
- Tianjin Medical University Second Hospital
- Brief Summary
The main purpose of this study is to explore the feasibility of selecting treatment plans based on genomic variations guided by MTB in patients with advanced refractory solid tumors.
- Detailed Description
Using comprehensive genome sequencing to analyze recurrent and metastatic solid tumors that have failed previous conventional treatments, and matching possible targeted therapy drugs to screen for potential effective treatment drugs until tumor disease progression, and then continuing to monitor tumor resistance mutation signals and provide matching therapy,...
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 300
Inclusion Criteria
- Recurrent or metastatic malignant solid tumors diagnosed by histology or cytology;
- ECOG score 0-4 (3-4 points only for patients with tumor burden);
- Those who fail or cannot tolerate standard treatment, or those who refuse standard treatment;
- At least one measurable lesion that meets the RECIST 1.1 standard;
- Expected survival period ≥ 3 months;
- Age ≥ 18 years old;
- Tumor tissue blocks with sufficient formalin fixed paraffin embedding (FFPE), or chest or ascites with cancer cells detected during treatment (not less than 200ml), or excised metastatic lymph nodes, or peripheral blood (approximately 5m1) can be used for genetic testing;
- Understand and voluntarily participate in this study, and sign the informed consent form.
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Exclusion Criteria
- Patients who have actively undergone or are currently participating in clinical trials for treatment;
- Serious or uncontrolled medical diseases (i.e. uncontrolled diabetes, chronic kidney disease, chronic lung disease or uncontrolled active infection, mental diseases/social conditions that limit the compliance with the research requirements) that the researchers think will confuse the research treatment response analysis;
- Pregnant or lactating patients, or any patients with fertility, have not taken appropriate pregnancy prevention measures.
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Monotherapy Target Gene In the OncoKB(Precision Oncology Knowledge Base) database, the gene alteration has a variant of clinical evidence in this tumor or other tumor types and is considered to be an interventional variant. Cohort-1may include different observation subgroups（dMMR/MSI-H,TMB-H,NTRK fusion,RET-fusion,BRAF(p.V600E),KRAS(p.G12C),HER2(IHC,3+)）. For example, substudy-1: monotherapy/combination therapy for patients with A1-relative. Substudy-x: monotherapy/combination therapy for patients with Ax-relative. Combination therapy-cohort1 Olaparib tablet The characteristics of enrolled patients are the presence of two or more interventional or potential actionable targets(only TP53 alteration,MAP2K1 alteration,PMA pathway alteration,11q13 amplification,MET alteration). Combination therapy-cohort1 Temozolomide capsule The characteristics of enrolled patients are the presence of two or more interventional or potential actionable targets(only TP53 alteration,MAP2K1 alteration,PMA pathway alteration,11q13 amplification,MET alteration). Combination therapy-cohort1 Anlotinib The characteristics of enrolled patients are the presence of two or more interventional or potential actionable targets(only TP53 alteration,MAP2K1 alteration,PMA pathway alteration,11q13 amplification,MET alteration). Combination therapy-cohort1 Trametinib tablet The characteristics of enrolled patients are the presence of two or more interventional or potential actionable targets(only TP53 alteration,MAP2K1 alteration,PMA pathway alteration,11q13 amplification,MET alteration). Combination therapy-cohort1 Dabrafenib The characteristics of enrolled patients are the presence of two or more interventional or potential actionable targets(only TP53 alteration,MAP2K1 alteration,PMA pathway alteration,11q13 amplification,MET alteration). Combination therapy-cohort1 Vebreltinib Enteric Capsules The characteristics of enrolled patients are the presence of two or more interventional or potential actionable targets(only TP53 alteration,MAP2K1 alteration,PMA pathway alteration,11q13 amplification,MET alteration). Combination therapy-cohort1 Alpelisib Pill The characteristics of enrolled patients are the presence of two or more interventional or potential actionable targets(only TP53 alteration,MAP2K1 alteration,PMA pathway alteration,11q13 amplification,MET alteration). Combination therapy-cohort1 Sacituzumab Govitecan-Hziy 180 MG The characteristics of enrolled patients are the presence of two or more interventional or potential actionable targets(only TP53 alteration,MAP2K1 alteration,PMA pathway alteration,11q13 amplification,MET alteration). Combination therapy-cohort1 Lenvatinib Capsules The characteristics of enrolled patients are the presence of two or more interventional or potential actionable targets(only TP53 alteration,MAP2K1 alteration,PMA pathway alteration,11q13 amplification,MET alteration). Combination therapy-cohort1 Pazopanib Pill The characteristics of enrolled patients are the presence of two or more interventional or potential actionable targets(only TP53 alteration,MAP2K1 alteration,PMA pathway alteration,11q13 amplification,MET alteration). Combination therapy-cohort1 Palbociclib Pill The characteristics of enrolled patients are the presence of two or more interventional or potential actionable targets(only TP53 alteration,MAP2K1 alteration,PMA pathway alteration,11q13 amplification,MET alteration). Combination therapy-cohort1 Chidamide The characteristics of enrolled patients are the presence of two or more interventional or potential actionable targets(only TP53 alteration,MAP2K1 alteration,PMA pathway alteration,11q13 amplification,MET alteration). Combination therapy-cohort1 PD-1/PD-L1/PD-1&CTLA4 inhibitor The characteristics of enrolled patients are the presence of two or more interventional or potential actionable targets(only TP53 alteration,MAP2K1 alteration,PMA pathway alteration,11q13 amplification,MET alteration). Combination therapy-cohort1 Target Gene The characteristics of enrolled patients are the presence of two or more interventional or potential actionable targets(only TP53 alteration,MAP2K1 alteration,PMA pathway alteration,11q13 amplification,MET alteration). Combination therapy-cohort2 Olaparib tablet The characteristics of enrolled patients are primary or secondary drug resistance during treatment. Combination therapy-cohort2 Temozolomide capsule The characteristics of enrolled patients are primary or secondary drug resistance during treatment. Combination therapy-cohort2 Anlotinib The characteristics of enrolled patients are primary or secondary drug resistance during treatment. Combination therapy-cohort2 Trametinib tablet The characteristics of enrolled patients are primary or secondary drug resistance during treatment. Combination therapy-cohort2 Dabrafenib The characteristics of enrolled patients are primary or secondary drug resistance during treatment. Combination therapy-cohort2 Vebreltinib Enteric Capsules The characteristics of enrolled patients are primary or secondary drug resistance during treatment. Combination therapy-cohort2 Alpelisib Pill The characteristics of enrolled patients are primary or secondary drug resistance during treatment. Combination therapy-cohort2 Sacituzumab Govitecan-Hziy 180 MG The characteristics of enrolled patients are primary or secondary drug resistance during treatment. Combination therapy-cohort2 Lenvatinib Capsules The characteristics of enrolled patients are primary or secondary drug resistance during treatment. Combination therapy-cohort2 Pazopanib Pill The characteristics of enrolled patients are primary or secondary drug resistance during treatment. Combination therapy-cohort2 Palbociclib Pill The characteristics of enrolled patients are primary or secondary drug resistance during treatment. Combination therapy-cohort2 Chidamide The characteristics of enrolled patients are primary or secondary drug resistance during treatment. Combination therapy-cohort2 PD-1/PD-L1/PD-1&CTLA4 inhibitor The characteristics of enrolled patients are primary or secondary drug resistance during treatment. Combination therapy-cohort2 Target Gene The characteristics of enrolled patients are primary or secondary drug resistance during treatment. Olaparib+Anlotinib/Temozolomide Olaparib tablet The gene TP53 alteration that MTB combines with clinical practice and literature reports that can match targeted therapy is considered to be potential actionable targets. Olaparib+Anlotinib/Temozolomide Temozolomide capsule The gene TP53 alteration that MTB combines with clinical practice and literature reports that can match targeted therapy is considered to be potential actionable targets. Olaparib+Anlotinib/Temozolomide Anlotinib The gene TP53 alteration that MTB combines with clinical practice and literature reports that can match targeted therapy is considered to be potential actionable targets. Trametinib±Vebreltinib Trametinib tablet The gene MAP2K1 alteration that MTB combines with clinical practice and literature reports that can match targeted therapy is considered to be potential actionable targets. Trametinib±Vebreltinib Dabrafenib The gene MAP2K1 alteration that MTB combines with clinical practice and literature reports that can match targeted therapy is considered to be potential actionable targets. Alpelisib Alpelisib Pill The PMA(PI3K/mTOR/AKT ) pathway active alteration that MTB combines with clinical practice and literature reports that can match targeted therapy is considered to be potential actionable targets.This subgroup is not included in breast cancer patients. Palbociclib+Pazopanib Pazopanib Pill The gene alteration(Chromosome 11q13 amplification (CCND1, FGF3, FGF4, and FGF19)) that MTB combines with clinical practice and literature reports that can match targeted therapy is considered to be potential actionable targets. Palbociclib+Pazopanib Palbociclib Pill The gene alteration(Chromosome 11q13 amplification (CCND1, FGF3, FGF4, and FGF19)) that MTB combines with clinical practice and literature reports that can match targeted therapy is considered to be potential actionable targets. Vebreltinib Vebreltinib Enteric Capsules MET inhibitors have recently demonstrated clinical activity in patients with MET exon 14 (METex14)-skipping/MET-amplification. Combination therapy group based on PD-1/L1 immune checkpoint inhibitors Lenvatinib Capsules MTB combined with clinical practice and literature reports can not match the gene alteration of targeted therapy, which is considered as an irreversible gene alteration.This subgroup may use functional models (including but not limited to PDX(Patient-Derived Tumor Xenograft Model), organoids, etc.) for intervention therapy. Combination therapy group based on PD-1/L1 immune checkpoint inhibitors Chidamide MTB combined with clinical practice and literature reports can not match the gene alteration of targeted therapy, which is considered as an irreversible gene alteration.This subgroup may use functional models (including but not limited to PDX(Patient-Derived Tumor Xenograft Model), organoids, etc.) for intervention therapy. Combination therapy group based on PD-1/L1 immune checkpoint inhibitors PD-1/PD-L1/PD-1&CTLA4 inhibitor MTB combined with clinical practice and literature reports can not match the gene alteration of targeted therapy, which is considered as an irreversible gene alteration.This subgroup may use functional models (including but not limited to PDX(Patient-Derived Tumor Xenograft Model), organoids, etc.) for intervention therapy. Combination therapy group based on PD-1/L1 immune checkpoint inhibitors Target Gene MTB combined with clinical practice and literature reports can not match the gene alteration of targeted therapy, which is considered as an irreversible gene alteration.This subgroup may use functional models (including but not limited to PDX(Patient-Derived Tumor Xenograft Model), organoids, etc.) for intervention therapy.
- Primary Outcome Measures
Name Time Method PFS2/PFS1(Progression Free Survival 2/Progression Free Survival 1) 24 months The time to progression-free survival during the substudy (PFS2) exceeds the documented time to disease progression-free survival during the last treatment prior to substudy entry (PFS1) by at least 35% (ie, PFS2/PFS1≥1.3) or, if PFS1 is not evaluable, time to progressive disease exceeds 6 months.
- Secondary Outcome Measures
Name Time Method OS(Overall Survival) 24 months Evaluation of overall survival (OS) defined as the time between inclusion and death, whatever the cause is. Alive patients will be censored at their last known contact date.
ORR(Objective Response Rate) 24 months Evaluation of the best objective response rate (ORR) for each treatment according to RECIST 1.1. The best ORR is the best response reached during treatment according to RECIST 1.1 criteria.
Number of treatment related adverse events with grade 3 or greater severity by CTCAE 5.0 24 months Treatment related adverse events with grade 3 or greater severity by CTCAE 5.0.
Trial Locations
- Locations (1)
Tianjin Medical Unversity Second Hospital
🇨🇳Tianjin, Tianjin, China