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)
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)
Oki Eiji
Kyushu University Hospital
3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan
+81-92-641-1151
oki.eiji.857@m.kyushu-u.ac.jp
Yoshimoto Haruka
I'cros Co.,Ltd.
Tenjin, Chuo-ku, Fukuoka-shi, Fukuoka
+81-92-406-8278
gaia102_icros@iromgp.com
Recruiting
June. 18, 2022
Oct. 17, 2022
176
Interventional
randomized controlled trial
open(masking not used)
dose comparison control
parallel assignment
treatment purpose
1. Unresectable or advanced recurrent gastric cancer with evident peritoneal dissemination on imaging, or with malignant ascites, as well as unresectable or advanced recurrent pancreatic cancer.
2. Phase I:
Patients with gastric cancer who have received 3 or more prior chemotherapy regimens and are refractory or intolerant to these therapies, and patients with pancreatic cancer who have received 2 or more prior chemotherapy regimens and are refractory or intolerant to these therapies.
Phase II:
Patients with gastric cancer who have received 2 or more prior chemotherapy regimens, including at least 1 regimen containing an immune checkpoint inhibitor, and are refractory or intolerant to these therapies, and patients with pancreatic cancer who have received 1 or more prior chemotherapy regimens,including at least 1 regimen containing gemcitabine, and are refractory or intolerant to these therapies.
Only patients with HER2-negative gastric cancer are eligible.
3. Abdominal port placement is possible.
4. Phase I:
No medical history of serious adverse reactions or allergic reactions to pembrolizumab. (only for patients in the pembrolizumab combination cohort)
Phase II(gastric cancer):
No medical history of serious adverse reactions or allergic reactions to pembrolizumab or trifluridine/tipiracil hydrochloride(FTD/TPI),or to any components of these agents.
Phase II(pancreatic cancer):
No medical history of serious adverse reactions or allergic reactions to pembrolizumab, irinotecan hydrochloride hydrate, fluorouracil,or calcium levofolinate hydrate,or to any components of these agents.
5. Diagnosed gastric adenocarcinoma or pancreatic cancer with by histological or cytological examination.
6. The patient has been confirmed to be "negative (not MSS = MSI-high)" by microsatellite instability (MSI) testing, or "proficient mismatch repair (pMMR)" by mismatch repair protein immunohistochemistry testing.
7. The Eastern Cooperative Oncology Group (ECOG) Performance Status(PS) at the time of informed consent meets the following conditions.
- Phase I :0-2
- Phase II :0-1
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.
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 Cycle 1 Day 1.
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
*Staging laparoscopy, cytology, and biopsy performed in association with the placement of the intraperitoneal port for this clinical trial are not considered part of the surgery
-Palliative radiotherapy: 1 week
-Thoracic drainage: 1 week
-Pretreatment antineoplastic (from the last administration)
Phase I:3 weeks
Phase II:3 weeks(If the scheduled date of administration of the investigational drug is at least 3 weeks after the final administration date of the prior treatment, enrollment is allowed.)
-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.Phase II(gastric cancer only)
Patients with a history of treatment with trifluridine/tipiracil hydrochloride. (FTD/TPI)
18. Difficult to participate in the trial by the investigator.
20age old over
No limit
Both
Advanced gastrointestinal cancer of microsatellite stable
Phase I part
Administration of GAIA-102 as a monotherapy or GAIA-102 and pembrolizumab in combination.
- GAIA-102 as a monotherapy
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(gastric cancer)
Patients will be randomly assigned to receive either GAIA-102 monotherapy or GAIA-102 in combination with pembrolizumab at the recommended dosing regimen confirmed in the Phase I part, or to receive standard therapy.
For patients with gastric cancer, the standard therapy group will receive trifluridine/tipiracil hydrochloride (FTD/TPI) only.
Phase II part(pancreatic cancer)
A run-in cohort will be conducted in which patients will receive GAIA-102 and Pembrolizumab in combination with standard therapy at the recommended dosing regimen confirmed in the Phase I part.
After confirming safety, patients will be randomly assigned to either GAIA-102 and Pembrolizumab in addition to standard therapy or standard therapy alone.
For patients with pancreatic cancer, the standard therapy group will receive irinotecan hydrochloride hydrate, fluorouracil, and calcium levofolinate hydrate only.
gastric cancer, pancreatic cancer
Gastrointestinal Neoplasms
Phase I part
-Presence or absence of DLT expression
-Frequency and severity of adverse events
Phase II part
-Overall survival
Phase I part
- Objective Response Rate and Disease Control Rate
- Progression-free Survival
- Overall Survival Period
- 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
- One-year survival rate
- Frequency and severity of adverse events
- Research of Biomarkers (serum, seroperitoneum)
Japan Agency for Medical Research and Development
Not applicable
GAIA BioMedicine Inc.
Not applicable
Kyushu University Hospital Institutional Review Board
