Efficacy and Safety of Precision Therapy in Refractory Tumor

Study Overview
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Brief Summary
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This study is intended to evaluate efficacy and safety of targeted precision therapy in patients with refractory tumor, including rare tumor without standard recommended treatment and common tumor after multiple line of therapy.

Detailed Description
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The individuals recruited in the present study are with solid tumor, mainly including two parts: first, rare tumor without standard recommended treatment such as atypical fibrous histiocytoma; second, common tumor after multiple line of therapy such as lung cancer, gastric cancer, colorectal cancer, etc. All patients have no any standard therapy based on NCCN guideline when recruiting. Next-generation sequence was used to detect druggable molecular event including gene mutation, gene fusion, amplification, etc. Then patients with molecular events were treated with corresponding targeted drug and followed-up, and not limited tumor type. PD-1/L1 inhibior plus anti-angiogenic agent was used in patients without durgguable targets. The efficacy and safety of these regimens were evaluated.

Official Title
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Efficacy and Safety of Precision Therapy in Refractory Tumor (Long March Pathway)

Conditions
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Rare Tumor, Refractory Tumor

Intervention / Treatment
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* Drug: Gefitinib
* Drug: Erlotinib
* Drug: Afatinib
* Drug: Trastuzumab
* Drug: Oxazolidine
* Drug: Olaparib
* Drug: Everolimus
* Drug: Cabozantinib
* Drug: Vemurafenib
* Drug: Dabrafenib
* Drug: Palbociclib
* Drug: PD-1/L1 inhibitor plus anti-angiogenic agent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Malignant solid tumors diagnosed histologically; Common solid tumor patients have no any standard choice after multiple line of therapy; Rare solid tumor did not have any standard recommended treatment; Expected survival ≥ 1 month; ECOG / PS score: 0-2, and the main organ function to meet the following criteria: HB ≥ 90g / L, ANC ≥ 1.5 × 109 / L, PLT ≥ 80 × 109 / L,BIL <1.5 times the upper limit of normal (ULN); Liver ALT and AST <2.5 × ULN and if liver metastases, ALT and AST <5 × ULN; Serum Cr ≤ 1 × ULN, endogenous creatinine clearance ≥50ml/min Exclusion Criteria: Patient still has standard treatment therapy based on NCCN guidance; Patient can not comply with research program requirements or follow-up;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Targeted Drug Therapy Group<br>All recruited patients with druggable molecular event will be treated with corresponding targeted drug including Gefitinib/Erlotinib/Afatinib, Trastuzumab, Oxazolidine, Olaparib, Everolimus, Cabozantinib, Vemurafenib/Dabrafenib, and Palbociclib. If no durggable target, PD-1/L1 inhibitor plus anti-angiogenic agent was used. | Drug: Gefitinib<br>* Gefitinib is an FDA/CFDA approved targeted drugs used for EGFR mutation based on NGS results.<br>Drug: Erlotinib<br>* Erlotinib is an FDA/CFDA approved targeted drugs used for EGFR mutation based on NGS results.<br>Drug: Afatinib<br>* Afatinib is an FDA/CFDA approved targeted drugs used for EGFR mutation based on NGS results.<br>Drug: Trastuzumab<br>* Trastuzumab is an FDA/CFDA approved targeted drugs used for Her2 amplification based on NGS results.<br>Drug: Oxazolidine<br>* Oxazolidine is an FDA/CFDA approved targeted drugs used for ALK or ROS-1 or MET fusion based on NGS results.<br>Drug: Olaparib<br>* Olaparib is an FDA/CFDA approved targeted drugs used for BRCA1/2 mutation based on NGS results.<br>Drug: Everolimus<br>* Everolimus is an FDA/CFDA approved targeted drugs used for mTOR or PI3KCA mutation based on NGS results.<br>Drug: Cabozantinib<br>* Cabozantinib is an FDA/CFDA approved targeted drugs used for RET mutation based on NGS results.<br>Drug: Vemurafenib<br>* Vemurafenib is an FDA/CFDA approved targeted drugs used for BRAF mutation based on NGS results.<br>Drug: Dabrafenib<br>* Dabrafenib is an FDA/CFDA approved targeted drugs used for BRAF mutation based on NGS results.<br>Drug: Palbociclib<br>* Palbociclib is an FDA/CFDA approved targeted drugs used for CDK4/6 mutation or amplification based on NGS results.<br>Drug: PD-1/L1 inhibitor plus anti-angiogenic agent<br>* PD-1/L1 inhibitor plus anti-angiogenic agent is a regimen used for refractory tumor without druggable target<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Proportion of patients with reduction in tumor burden of a predefined amount, including complete remission and partial remission | Evaluation of tumor burden based on RECIST criteria through study completion, an average of 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress Free Survival | Time from treatment beginning until disease progression | Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 2 months | 
| Overall Survival | Time from treatment beginning until death from any cause | From date of treatment beginning until the date of death from any cause, through study completion, an average of 1 months | 
| Adverse Effect | Incidence of Treatment-related adverse Events | Through study completion, an average of 1 months |