GAIA-102 Intraperitoneal Administration in Patients With Advanced Gastrointestinal Cancer of Microsatellite Stable With Malignant Ascites
Primary Purpose
Gastric Cancer, Pancreatic Cancer
Status
Recruiting
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Phase I part
Phase II part
Sponsored by
About this trial
This is an interventional treatment trial for Gastric Cancer
Eligibility Criteria
Inclusion Criteria:
- Unresectable, advanced and relapsed gastric cancer with malignant ascites or unresectable, advanced and relapsed pancreatic cancer with malignant ascites
- 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)
- Abdominal port placement is possible
- No medical history of serious side effects or allergic reactions to pembrolizumab (only for patients in the pembrolizumab combination cohort)
- Diagnosed gastric adenocarcinoma or pancreatic cancerwith by histological or cytological examination
- Negative (MSS= not MSI-high) by microsatellite instability test
- Eastern Cooperative Oncology Group (ECOG) Performance status(PS) 0-2
- Patient aged 20years or older
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
- Expected to survive for 3 months or more at the enrollment
- Written informed consent
Exclusion Criteria:
- Untreated cranial metastases.
- Diagnosed with meningeal carcinomatosis
- Received allogeneic hematopoietic stem cell transplantation
- 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.
- Existence or suspected active autoimmune disease
- 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
- 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.
- Have active double cancer and need treatment for the double cancer
- Requires treatment as shown in "Unacceptable Combination / Supportive Therapy" during the clinical trial period
- Have a medical history of severe hypersensitivity to immune checkpoint inhibitors or immune-related adverse events requiring treatment
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
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
- Scheduled thoracotomy or abdominal surgery during the clinical trial period
- It is judged that it is difficult to enroll in this study due to clinically significant mental illness.
- Pregnant women, lactating women, women who are currently pregnant, or have no intention of contraception for 4 months after consent is obtained.
- Allergic to antibiotics and foreign animal-derived ingredients (pig and mouse)
- Difficult to participate in the trial by the investigator
Sites / Locations
- Kyushu University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
GAIA-102 as a single agent
GAIA-102 and pembrolizumab in combination
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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
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.
Secondary Outcome Measures
Objective Response Rate (ORR) and Disease Control Rate (DCR)(Phase I)
Progression-free Survival(Phase I)
Overall Survival(Phase I)
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.
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
Objective Response Rate Disease Control Rate(Phase II)
Progression-free Survival (Phase II)
Objective Response Period and Period until Objective Response (Phase II)
Overall Survival (Phase II)
Frequency and severity of adverse events (Phase II)
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05438459
Brief Title
GAIA-102 Intraperitoneal Administration in Patients With Advanced Gastrointestinal Cancer of Microsatellite Stable With Malignant Ascites
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 8, 2022 (Actual)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
June 8, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Kyushu University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer, Pancreatic Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
96 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
GAIA-102 as a single agent
Arm Type
Experimental
Arm Description
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.
Arm Title
GAIA-102 and pembrolizumab in combination
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Phase I part
Intervention Description
Administration of GAIA-102 as a single agent or GAIA-102 and pembrolizumab in combination.
Intervention Type
Biological
Intervention Name(s)
Phase II part
Intervention Description
Randomized into group of administration of GAIA-102 as a single agent or GAIA-102 or pembrolizumab in combination, group of standard treatment
Primary Outcome Measure Information:
Title
Number of participants of Dose Limiting Toxicity (DLT) with GAIA-102 (Phase I)
Description
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
Time Frame
Cycle 1 (Cycle period is 28 days)
Title
Progression Free Survival (PFS) rate at 6 months (Phase II)
Description
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.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR) and Disease Control Rate (DCR)(Phase I)
Time Frame
Week 24
Title
Progression-free Survival(Phase I)
Time Frame
2 year
Title
Overall Survival(Phase I)
Time Frame
2 year
Title
Pharmacokinetics of GAIA-102(Phase I)
Description
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.
Time Frame
pre-dose
Title
Biomarker of GAIA-102(Phase I)
Description
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
Time Frame
pre-dose
Title
Objective Response Rate Disease Control Rate(Phase II)
Time Frame
2 year
Title
Progression-free Survival (Phase II)
Time Frame
2 year
Title
Objective Response Period and Period until Objective Response (Phase II)
Time Frame
2 year
Title
Overall Survival (Phase II)
Time Frame
2 year
Title
Frequency and severity of adverse events (Phase II)
Time Frame
2 year
Title
Biomarker of GAIA-102(Phase II)
Description
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
Time Frame
pre-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Unresectable, advanced and relapsed gastric cancer with malignant ascites or unresectable, advanced and relapsed pancreatic cancer with malignant ascites
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)
Abdominal port placement is possible
No medical history of serious side effects or allergic reactions to pembrolizumab (only for patients in the pembrolizumab combination cohort)
Diagnosed gastric adenocarcinoma or pancreatic cancerwith by histological or cytological examination
Negative (MSS= not MSI-high) by microsatellite instability test
Eastern Cooperative Oncology Group (ECOG) Performance status(PS) 0-2
Patient aged 20years or older
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
Expected to survive for 3 months or more at the enrollment
Written informed consent
Exclusion Criteria:
Untreated cranial metastases.
Diagnosed with meningeal carcinomatosis
Received allogeneic hematopoietic stem cell transplantation
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.
Existence or suspected active autoimmune disease
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
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.
Have active double cancer and need treatment for the double cancer
Requires treatment as shown in "Unacceptable Combination / Supportive Therapy" during the clinical trial period
Have a medical history of severe hypersensitivity to immune checkpoint inhibitors or immune-related adverse events requiring treatment
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
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
Scheduled thoracotomy or abdominal surgery during the clinical trial period
It is judged that it is difficult to enroll in this study due to clinically significant mental illness.
Pregnant women, lactating women, women who are currently pregnant, or have no intention of contraception for 4 months after consent is obtained.
Allergic to antibiotics and foreign animal-derived ingredients (pig and mouse)
Difficult to participate in the trial by the investigator
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eiji Oki
Phone
+81-92-642-5479
Email
oki.eiji.857@m.kyushu-u.ac.jp
Facility Information:
Facility Name
Kyushu University Hospital
City
Fukuoka-shi
State/Province
Fukuoka, Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eiji Oki
Phone
+81-92-642-5479
Email
oki.eiji.857@m.kyushu-u.ac.jp
12. IPD Sharing Statement
Learn more about this trial
GAIA-102 Intraperitoneal Administration in Patients With Advanced Gastrointestinal Cancer of Microsatellite Stable With Malignant Ascites
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