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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastrointestinal Cancer
• Intervention / Treatment: Device: QPOP

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 119074
    • Recruiting
    • National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

At least 20 patients with gastric cancer, and 80 patients with other GI cancers will be first be recruited.

Description

Inclusion Criteria:

-

Patients may be included in the study only if they meet the following criteria:

1. 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
2. Chemo-refractory patients with GI cancers deemed by investigator to be fit for clinical trial
3. Age ≥ 21 years
4. ECOG PS 0-1
5. At least 1 tumour lesion amenable to fresh biopsy
6. At least 1 measurable tumour lesion based on RECIST v 1.1 criteria
7. Estimated life expectancy of at least 24 weeks

8. Adequate organ function , including:

   1. 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

   2. 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
9. Signed informed consent from patient or legal representative
10. Able to comply with study-related procedures.
11. Recovery from prior toxicity to G1, excluding alopecia.

Exclusion Criteria:

• There are no specific exclusion criteria if patients meet the inclusion criteria

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patient; Patient with first-line gastrointestinal cancers and patient with advanced and refractory GI cancers (>1 line of treatment), or post-progression biopsy)

Device: QPOP; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore

Publications and helpful links

General Publications

• Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012 Jul 18;487(7407):330-7. doi: 10.1038/nature11252.
• AACR Project GENIE Consortium. AACR Project GENIE: Powering Precision Medicine through an International Consortium. Cancer Discov. 2017 Aug;7(8):818-831. doi: 10.1158/2159-8290.CD-17-0151. Epub 2017 Jun 1.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2020
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: August 26, 2020
• First Submitted That Met QC Criteria: October 26, 2020
• First Posted (Actual): November 2, 2020

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: April 4, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Qpop
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Gastrointestinal Diseases; Gastrointestinal Neoplasms
• Other Study ID Numbers: 2019/00924

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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