Drug Sensitivity Screening for Gastrointestinal Cancer

Personalized Drug Sensitivity Test for Late Stage, Potentially Operable Gastrointestinal Cancer Using Patient Derived Primary Cell Culture

Explore the clinical feasibility of using primary cell culture system to guide gastrointestinal cancer chemotherapy, and establish the correlation between ex vivo drug sensitivity and patient clinical response.

Study objectives: Personalized drug sensitivity test for late stage,potentially operable gastrointestinal cancer using patient derived primary cell culture.

Explore the clinical feasibility of using primary cell culture system to guide gastrointestinal cancer chemotherapy, and establish the correlation between ex vivo drug sensitivity and patient clinical response.

The study will collect primary tumor tissues from stage III/IV gastrointestinal cancer patients who underwent emergency surgeries, and then establish the primary tumor cell library for ex vivo chemotherapy drug sensitivity test in order to:

1. Compare the ex vivo Maximal Inhibition Index(MI) and Drug Sensitivity Index (DSI) with patient's Overall Response Rate (ORR)
2. Provide research support for future clinical treatment.

This ex vivo method applies to single or combination drug regimen, and does not require prior knowledge of the specific mechanism for individual patient's drug sensitivity. Previous research as well as literature studies support the close relationship between ex vivo drug sensitivity and in vivo drug response.

Study Overview

• Status: Unknown
• Conditions: Gastrointestinal Cancer Metastatic
• Intervention / Treatment: Diagnostic test: Personalized drug sensitivity test

Detailed Description

The patient underwent surgery to remove tumor and agreed to take out the abdominal tumor specimens for research. A section of each sample was removed for the generation of PDX models as described early.The rest of the tumor cells were expanded using ex vivo drug sensitivity assay.

The drugs used in the study were 5-fluorouracil, Oxaliplatin, and irinotecan at C0 = 10 mM, 2.5 mM and 0.02 mM, respectively. They were applied either as single agents or in combinations of 5-fluorouracil and Oxaliplatin, 5-fluorouracil and irinotecan, or all three agents, or others. After 7 days of treatment, the tumor cells were stained with EdU, Hoechst and EpCAM with the Cell Quantitative Detection Kit. Images were acquired with an automated microscopic image-scanning system and analyzed with the built-in software.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yingjie Li, M.D.; Phone Number: +86 13520186618; Email: liyingjiedr@sina.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Sub-Investigator: Yingjie Li, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult patients between 18 and 70 years old, male or female;
2. Voluntary patient consent；
3. Treatment-naïve, stage III/IV gastrointestinal cancer patients with pathology confirmation；
4. According clinical researcher, patient has operable tumor lesion, and tumor tissue can be obtained through surgical removal;
5. Good tolerability to standard chemotherapy regimen；
6. ECOG status <3；
7. Estimated survival time no less than 6 months；
8. Patient has at least one measurable disease lesion (according to RECIST1.1).

Exclusion Criteria:

1. Patient has received any prior anti-cancer treatment;
2. Participated in any other clinical study within 6 months;
3. Women currently breast feeding or pregnant;
4. Severe liver or kidney function impairment (Live function: TBIL ≤1.5×ULN，ALT & AST≤2.5×ULN);
5. Patients with liver metastasis ≤5.0×ULN；Kidney function：Cr ≤1.5×ULN and creatinine clearance rate≥ 50 mL/min (according to the Cockcroft-Gault formula);
6. Patients with cognitive impairment, psychological disease, or poor compliance;
7. Allergic to known chemotherapy ingredients;
8. Other factors researchers deemed not suitable for study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: stage III/IV gastrointestinal cancer patients; The study group (Personalized drug sensitivity test) was treated according to the physician's opinion. Tumor tissues are obtained during the surgery or via biopsy with informed consent, for the purpose of ex vivo assay.

Diagnostic test: Personalized drug sensitivity test; The patients underwent surgery to remove tumor and took out tumor specimens for research. The tumor cells were expanded ex vivo drug sensitivity assay. The drugs used in the study were 5-fluorouracil, Oxaliplatin, and irinotecan at C0 = 10 mM, 2.5 mM and 0.02 mM, respectively. They were applied either as single agents or in combinations of 5-fluorouracil and Oxaliplatin, 5-fluorouracil and irinotecan, or all three agents, or others. After 7 days of treatment, the tumor cells were stained with EdU, Hoechst and EpCAM with the Cell Quantitative Detection Kit. Images were acquired with an automated microscopic image-scanning system and analyzed with the built-in software.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ex vivo Maximal Inhibition Index (MI)	The effectiveness of each therapeutic regimen was evaluated and quantified using the formula: Maximum Inhibition (MI)=N0/Nd, where N0 and Nd denotes the number of EpCAM+ EdU+ epithelial cells in the wells of control or withthe drug at concentration C0, respectively.	1 month after the tissue acquisition

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate（DCR）after chemotherapy	Disease Control Rate（DCR）after chemotherapy.	3 months after chemotherapy
Progression free survival (PFS) after chemotherapy	Progression free survival (PFS) after chemotherapy	1 year after chemotherapy

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Anticipated): April 30, 2022
• Study Completion (Anticipated): April 30, 2022

Study Registration Dates

• First Submitted: December 10, 2018
• First Submitted That Met QC Criteria: March 5, 2020
• First Posted (Actual): March 6, 2020

Study Record Updates

• Last Update Posted (Actual): March 6, 2020
• Last Update Submitted That Met QC Criteria: March 5, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Chemotherapy; Personalized; Drug Sensitivity Test
• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Gastrointestinal Diseases; Hypersensitivity; Gastrointestinal Neoplasms
• Other Study ID Numbers: PKUCH-M01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No