Neural Network-based Treatment Decision Support Tool in Patients With Refractory Solid Organ Malignancies

Study Overview
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Brief Summary
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DRUID is a treatment decision support tool combining predictive models and public databases related to multi-gene markers, drug response screens, gene essentiality and clinical status of drugs to provide drug recommendations personalized based on an input genomic profile. We hypothesize that DRUID analysis of patients' somatic mutational profile from NGS diagnostic platform can be used as a treatment decision support tool in patients with refractory cancer without targetable mutations.

Detailed Description
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2.1. Hypothesis We hypothesize that DRUID analysis of patients' somatic mutational profile from NGS diagnostic platform can be used as a treatment decision support tool in patients with refractory cancer without targetable mutations. Using algorithm selected treatment from a panel of 60 drugs we predict an objective response rate (ORR) of ≥ 25%. 2.2. Primary Objectives • To prospectively determine if DRUID selected therapy based on NGS diagnostic profile input can lead to objective responses in refractory solid organ malignancies. 2.3. Secondary Objectives To assess clinical benefit rate (complete response, partial response and stable disease for ≥ 24 weeks) To assess progression-free and overall survival of patients treated with DRUID-guided therapy

Official Title
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A Phase II Trial of Neural Network-based Treatment Decision Support Tool in Patients With Refractory Solid Organ Malignancies

Conditions
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Solid Organ Malignancies

Intervention / Treatment
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* Other: DRUID AI Program


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients may be included in the study only if they meet all of the following criteria: Age ≥ 21 years. Histological or cytological diagnosis solid organ malignancy Available results of comprehensive NGS panel testing performed on either tumour tissue or blood-based assay. If results are from blood-based assay, test must have been performed in the metastatic setting. ECOG 0-2. At least 1 measurable tumour lesions based on RECIST 1.1 criteria Estimated life expectancy of at least 12 weeks. Has documented progressive disease from last line of therapy. Has received at least 2 lines of palliative systemic therapy with no available standard therapy: Adequate organ function including the following: Bone marrow: Absolute neutrophil (segmented and bands) count (ANC) ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L Haemoglobin ≥ 8 x 109/L Hepatic: Bilirubin ≤ 1.5 x upper limit of normal (ULN), ALT or AST ≤ 2.5x ULN, (or ≤ 5 X with liver metastases) Renal: Creatinine ≤ 1.5x ULN Signed informed consent from patient or legal representative. Able to comply with study-related procedures. Exclusion Criteria: Treatment within the last 30 days with any investigational drug. Concurrent administration of any other tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy. Major surgery within 28 days of study drug administration. Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy. Pregnancy. Breast feeding. Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator. Active bleeding disorder or bleeding site. Non-healing wound. Second primary malignancy that is clinically detectable at the time of consideration for study enrolment. Symptomatic brain metastasis.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 99 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
Interventional Model Description: Patients NGS profile will be analysed with DRUID system to generate recommendations based on predicted efficacy. Patients with available archival tissue will have gene expression analysis performed to optimise DRUID recommendation. Patients will subsequently receive single agent therapy based on DRUID recommendations and criteria for therapy choice. Patients will begin single agent therapy within 4 weeks of enrolment and continue until disease progression, maximum safe cumulative dose reached (where applicable, per standard institution practice) or unacceptable toxicity as per physician's discretion.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DRUID<br>Patients NGS profile will be analysed with DRUID system to generate recommendations based on predicted efficacy. Patients with available archival tissue will have gene expression analysis performed to optimise DRUID recommendation. Patients will subsequently receive single agent therapy based on DRUID recommendations and criteria for therapy choice. | Other: DRUID AI Program<br>* Patients will begin single agent therapy within 4 weeks of enrolment and continue until disease progression, maximum safe cumulative dose reached (where applicable, per standard institution practice) or unacceptable toxicity as per physician's discretion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Defined as patient exhibiting a best study response of complete or partial clinical response based on radiological imaging per RECIST 1.1 criteria. | 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit | Defined as presence of best study response of complete or partial response or stable disease for at least 24 weeks (based on RECIST 1.1 criteria). | 10 months | 
| Progression free survival | Defined as the time from the date of study enrolment to the first date of documented disease progression. | From enrolment till disease progression or date of death or final follow-up visit (1 year). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Next generation sequencing, DRUID