Clinical trial NCT04298489: Drug Sensitivity Screening for Gastrointestinal Cancer
Official title: Personalized Drug Sensitivity Test for Late Stage, Potentially Operable Gastrointestinal Cancer Using Patient Derived Primary Cell Culture
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Gastrointestinal Cancer Metastatic
Keywords: Personalized
Drug Sensitivity Test
Chemotherapy
Lead sponsor: Peking University Cancer Hospital & Institute
Sponsor class: OTHER
First posted: 2020-03-06
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: ex vivo Maximal Inhibition Index (MI)
timeFrame: 1 month after the tissue acquisition
Secondary outcomes:
measure: Disease Control Rate（DCR）after chemotherapy
timeFrame: 3 months after chemotherapy
measure: Progression free survival (PFS) after chemotherapy
timeFrame: 1 year after chemotherapy
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Aiwen Wu, M.D.
role: PRINCIPAL_INVESTIGATOR
References: