Drug Sensitivity Screening for Gastrointestinal Cancer

Gastrointestinal Cancer Metastatic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04298489
• Other study ID #: PKUCH-M01
• Status: Recruiting
• Phase: N/A
• Start date: May 1, 2017
• Est. completion date: April 30, 2022

Study information

• Verified date: March 2020
• Source: Beijing Cancer Hospital
• Contact: Yingjie Li, M.D.
• Phone: +86 13520186618
• Email: liyingjiedr[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: April 30, 2022
• Est. primary completion date: April 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Gastrointestinal Cancer Metastatic
• Gastrointestinal Neoplasms
• Hypersensitivity

Intervention

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.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Cancer Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Disease Control Rate(DCR)after chemotherapy	Disease Control Rate(DCR)after chemotherapy.	3 months after chemotherapy
Secondary	Progression free survival (PFS) after chemotherapy	Progression free survival (PFS) after chemotherapy	1 year after chemotherapy