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)

JRCT ID: jRCT2073220017

Registered date:18/06/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Advanced gastrointestinal cancer of microsatellite stable
• Date of first enrollment: 17/10/2022
• Target sample size: 96
• Study type: Interventional

Intervention(s)

Phase I part
Administration of GAIA-102 as a single agent or GAIA-102 and pembrolizumab in combination.
- GAIA-102 as a single agent
GAIA-102: 1 vial (2 x 10^8 cells) as dose at a fixeddose, on 1 to 3 times by weekly for 3 consecutive weeks.
- 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.

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

Outcome(s)

Primary Outcome

Phase I part
-Presence or absence of DLT expression
-Frequency and severity of adverse events
Phase II part
-6 month survival rate

Secondary Outcome

Phase I part
- Objective Response Rate and Disease Control Rate
- Progression-free Survival
- Overall Survival
- Pharmacokinetics of GAIA-102 (In the blood)
- Research of Biomarkers (serum, seroperitoneum)
Phase II part
- Objective Response Rate and Disease Control Rate
- Progression-free Survival
- Objective Response Period and Period until Objective Response
- Overall Survival
- Frequency and severity of adverse events
- Research of Biomarkers (serum, seroperitoneum)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include 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)
-eGFR >=30mL/min/1.73m2
10. Expected to survive for 3 months or more at the enrollment
11. Written informed consent

Exclude 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 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

Related Information

• Primary Sponsor: Oki Eiji
• Secondary Sponsor: Yonemitsu Yoshikazu
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development