Q-GAIN (Using Qpop to Predict Treatment for GAstroIntestinal caNcer)

Study Overview
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Brief Summary
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This is a multi-cohort proof of concept study involving patients with metastatic gastrointestinal cancers. In the first cohort of treatment-naïve patients, the investigators intend to create cancer organoids for 100 subjects. Then, the investigators intend to evaluate ex-vivo prediction of treatment outcomes using QPOP (see section 4.0 for detailed sample size calculation). Patients enrolled on study will undergo a fresh biopsy of tumour lesion to obtain cells that will be used to generate patient-derived tumour organoids. These patients will go on to receive standard of care first-line chemotherapy +/- targeted therapy. Organoids will then be subjected to up to a 14-drug panel screening. The drugs in the respective drug panel have been shown to have activity in the respective cancers and would be used in the standard-of-care setting by treating physicians.

Detailed Description
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Hypothesis: Ex-vivo sensitivity testing on patient derived tumour organoids using QPOP can identify drug combinations which may have clinical efficacy against metastatic gastrointestinal cancer. Specific aim 1: To grow patients' gastrointestinal tumour-derived organoids. Specific aim 2: To perform ex-vivo drug sensitivity testing on patient derived tumour organoids using QPOP for metastatic gastrointestinal cancers. Specific aim 3: Asses the efficacy of phenotype directed therapy using QPOP to assign treatment after progression of standard of chemo for gastric cancer.

Official Title
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Q-GAIN (Using Qpop to Predict Treatment for GAstroIntestinal caNcer)

Conditions
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Gastrointestinal Cancer

Intervention / Treatment
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* Device: QPOP


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 the following criteria: Treatment naïve patient with gastrointestinal cancers (i.e. oesophageal, gastro-oesophgeal, gastric, small bowel, colorectal, hepatocellular, pancreatic and biliary tract) fit and planned for first line treatment, OR Chemo-refractory patients with GI cancers deemed by investigator to be fit for clinical trial Age ≥ 21 years ECOG PS 0-1 At least 1 tumour lesion amenable to fresh biopsy At least 1 measurable tumour lesion based on RECIST v 1.1 criteria Estimated life expectancy of at least 24 weeks Adequate organ function , including: Pre-biopsy o Bone marrow: Absolute neutrophil (segmented and bands) count (ANC) ≥1.5 x 109/L Platelets ≥ 100 x 109/L Pro-Thrombin within ULN Hemoglobin ≥ 8 x 109/L Pre-treatment Bone marrow: Absolute neutrophil (segmented and bands) count (ANC) ≥1.5 x 109/L Platelets ≥ 100 x 109/L Hemoglobin ≥ 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. Recovery from prior toxicity to G1, excluding alopecia. Exclusion Criteria: There are no specific exclusion criteria if patients meet the inclusion criteria

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patient<br>Patient with first-line gastrointestinal cancers and patient with advanced and refractory GI cancers (>1 line of treatment), or post-progression biopsy) | Device: QPOP<br>* QPOP will then be applied to establish the most efficacious drug combination for the specific organoid. Additional drugs other than those listed above may be screened depending on availability of cancer organoids. When patients progress after first-line treatment, QPOP generated second-line options will be informed to treating physicians and the physician will exercise his/her discretion to select the most suitable drug based on patient's comorbidities and organ function after a formal molecular/phenotype tumour board.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of radiological response | complete and partial clinical response, including confidence intervals. | 3 years | 
| Percentage of patients with successful organoid generation for each different tumour type. | Patients enrolled on study will undergo a fresh biopsy of tumour lesion to obtain cells that will be used to generate patient-derived tumour organoids. | 3 years | 
| Efficacy of second-line therapy | measured by Overall Response Rate for patients with gastric cancer. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haematologic and non-haematologic toxicities | Toxicity rating using the NCI CTC v4.03 scale | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Qpop