GAIA-102 Intraperitoneal Administration in Patients With Advanced Gastrointestinal Cancer of Microsatellite Stable With Malignant Ascites

Clinical Trial of Repeated Intraperitoneal Administration of GAIA-102 in Patients With Advanced Gastrointestinal Cancer (Gastric Cancer / Pancreatic Cancer) of Microsatellite Stable (MSS) With Malignant Ascites (Phase I / II Investigator-initiated Clinical Trial) (GAIA-102-PD Clinical Trial)

Phase I Part :

Confirm the safety of GAIA-102 GAIA-102 as a single agent or GAIA-102 and pembrolizumab in combination for Advanced gastrointestinal cancer of microsatellite stable with malignant ascites, and determine the recommended number of doses for Phase II part.

Phase II Part :

Research the efficacy and safety of as a single agent or GAIA-102 and pembrolizumab for Advanced gastrointestinal cancer of microsatellite stable with malignant ascites at the recommended dose of GAIA-102 decided in the Phase I part.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Pancreatic Cancer
• Intervention / Treatment: Biological: Phase I part; Biological: Phase II part

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Eiji Oki; Phone Number: +81-92-642-5479; Email: oki.eiji.857@m.kyushu-u.ac.jp

Study Locations

• Japan
  • Fukuoka, Fukuoka
    • Fukuoka-shi, Fukuoka, Fukuoka, Japan, 812-8582
      • Recruiting
      • Kyushu University Hospital
      • Contact: Eiji Oki; Phone Number: +81-92-642-5479; Email: oki.eiji.857@m.kyushu-u.ac.jp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Unresectable, advanced and relapsed gastric cancer with malignant ascites or unresectable, advanced and relapsed pancreatic cancer with malignant ascites
2. Refractory/intolerant to more than 3 regimens of therapy for gastric cancer (more than 2 regimens acceptable for Phase II) or more than 2 regimens of therapy for pancreatic cancer (more than 1 regimen acceptable for Phase II)
3. Abdominal port placement is possible
4. No medical history of serious side effects or allergic reactions to pembrolizumab (only for patients in the pembrolizumab combination cohort)
5. Diagnosed gastric adenocarcinoma or pancreatic cancerwith by histological or cytological examination
6. Negative (MSS= not MSI-high) by microsatellite instability test
7. Eastern Cooperative Oncology Group (ECOG) Performance status(PS) 0-2
8. Patient aged 20years or older

9. Adequate major organs (bone marrow, heart, lungs, liver, kidneys, etc.) function:

   • Neutrophil >1,500/mm3
   • hemoglobin >=8.0 g/dL
   • Platelet >75,000/mm3
   • PT-INR <1.5 -AST, ALT <=3 times the upper limit of reference value
   • T-Bil <=2 times the upper limit of reference value (T-Bil <=3.0mg/dL , when drainage for obstructive jaundice)
   • Serum creatinine <=1.5mg/dL
   • CCr >=30mL/min
10. Expected to survive for 3 months or more at the enrollment
11. Written informed consent

Exclusion Criteria:

1. Untreated cranial metastases.
2. Diagnosed with meningeal carcinomatosis
3. Received allogeneic hematopoietic stem cell transplantation
4. Participated in other clinical trials / clinical trials within 30 days prior to obtaining written consent and used or had used the investigational product or investigational equipment.
5. Existence or suspected active autoimmune disease
6. Continued systemic immunosuppressive therapy with corticosteroids in excess of 10 mg / day in terms of prednisolone or other immunosuppressants within 14 days prior to investigational product administration
7. Symptomatic interstitial pneumonia, or even if it is not symptomatic, it may interfere with diagnostic imaging in detecting new pneumonitis caused by the investigational product used in the clinical trial.
8. Have active double cancer and need treatment for the double cancer
9. Requires treatment as shown in "Unacceptable Combination / Supportive Therapy" during the clinical trial period
10. Have a medical history of severe hypersensitivity to immune checkpoint inhibitors or immune-related adverse events requiring treatment

11. Have one of the following complications

    • Complication of cerebrovascular disorder with symptoms or history within 6 months before the enrollment
    • Active gastrointestinal perforation, fistula, diverticulitis
    • Symptomatic congestive heart failure
    • Bleeding tendency
    • Presence of blood clots that may cause embolism on the image
    • Unhealed fractures (excluding compression fractures associated with osteoporosis) or severe wounds requiring medical treatment
    • Uncontrollable digestive ulcer
    • Active infectious diseases requiring intravenous administration of antibiotics, antifungal agents or antiviral agents
    • HIV antibody positive

12. At the time of the enrollment, the period from the following prior treatment or the end of treatment has not passed.

    • Surgery (including exploratory laparotomy / examination laparoscope): 2 weeks
    • Palliative radiotherapy: 1 week
    • Thoracic drainage: 1 week
    • Pretreatment antineoplastic (from the last administration): 3 weeks
    • Biopsy with incision, thoracic biopsy, treatment for trauma (excluding patients without wound healing), etc : 2 weeks
13. Scheduled thoracotomy or abdominal surgery during the clinical trial period
14. It is judged that it is difficult to enroll in this study due to clinically significant mental illness.
15. Pregnant women, lactating women, women who are currently pregnant, or have no intention of contraception for 4 months after consent is obtained.
16. Allergic to antibiotics and foreign animal-derived ingredients (pig and mouse)
17. Difficult to participate in the trial by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GAIA-102 as a single agent; GAIA-102: 1 vial (2 x 10^8 cells) as dose at a fixed dose, on 1 to 3 times by weekly for 3 consecutive weeks.	Biological: Phase I part; Administration of GAIA-102 as a single agent or GAIA-102 and pembrolizumab in combination.; Biological: Phase II part; Randomized into group of administration of GAIA-102 as a single agent or GAIA-102 or pembrolizumab in combination, group of standard treatment
Experimental: GAIA-102 and pembrolizumab in combination; GAIA-102: 1 vial (2 x 10^8 cells) as dose at a fixed dose, on 1 to 3 times by weekly for 3 consecutive weeks. Pembrolizumab：200 mg on Day 1.	Biological: Phase I part; Administration of GAIA-102 as a single agent or GAIA-102 and pembrolizumab in combination.; Biological: Phase II part; Randomized into group of administration of GAIA-102 as a single agent or GAIA-102 or pembrolizumab in combination, group of standard treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants of Dose Limiting Toxicity (DLT) with GAIA-102 (Phase I)	DLT was evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and is defided following events: 1. Grade 4 hemotoxicity or hemotoxicity requiring blood transfusion. 2. Grade 3 or higher non-hematoxicity	Cycle 1 (Cycle period is 28 days)
Progression Free Survival (PFS) rate at 6 months (Phase II)	PFS rate at 6 months was defined as the rate of surviving participants who survived or were not determined as progressive at 6 months from the day of enrollment.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate （ORR) and Disease Control Rate (DCR)(Phase I)		Week 24
Progression-free Survival(Phase I)		2 year
Overall Survival(Phase I)		2 year
Pharmacokinetics of GAIA-102(Phase I)	The following metrics were meassured as pharmcokinetics; Cmax: The peak plasma concentration of a drug after administration.; tmax. : Time to reach Cmax; Cmin: The lowest (trough) concentration that a drug reaches before the next dose is administered.	pre-dose
Biomarker of GAIA-102(Phase I)	Protein expression levels are measured in ascites and blood as biomarkers. The following are the markers to be measured; CCL3/CCL4/CCL5/CCL20/CXCL9/CXCL10/CXCL11	pre-dose
Objective Response Rate Disease Control Rate(Phase II)		2 year
Progression-free Survival (Phase II)		2 year
Objective Response Period and Period until Objective Response (Phase II)		2 year
Overall Survival (Phase II)		2 year
Frequency and severity of adverse events (Phase II)		2 year
Biomarker of GAIA-102(Phase II)	Protein expression levels are measured in ascites and blood as biomarkers. The following are the markers to be measured; CCL3/CCL4/CCL5/CCL20/CXCL9/CXCL10/CXCL11	pre-dose

Collaborators and Investigators

• Sponsor: Kyushu University

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2022
• Primary Completion (Anticipated): December 31, 2026
• Study Completion (Anticipated): June 8, 2027

Study Registration Dates

• First Submitted: June 13, 2022
• First Submitted That Met QC Criteria: June 24, 2022
• First Posted (Actual): June 30, 2022

Study Record Updates

• Last Update Posted (Actual): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 24, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Stomach Neoplasms; Pancreatic Neoplasms; Ascites; Gastrointestinal Neoplasms
• Other Study ID Numbers: CTR024-001

Drug and device information, study documents

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