Clinical trial NCT05438459: 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
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Gastric Cancer
Pancreatic Cancer
Lead sponsor: Kyushu University
Sponsor class: OTHER
Collaborators: name: GAIA BioMedicine Inc.
name: Toho University - Omori Medical Center
name: Jichi Medical University
name: Kindai University Hospital
name: Teikyo University Hospital
name: Kansai Medical University Hospital
name: Kyushu Cancer Center
First posted: 2022-06-30
Enrollment: 96
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Phase I Part :

Confirm the safety of GAIA-102 as a monotherapy 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 monotherapy 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.


Eligibility criteria: Inclusion Criteria:

1. Unresectable or advanced recurrent gastric cancer with evident peritoneal dissemination on imaging, or with ascites, as well as unresectable or advanced recurrent pancreatic cancer.
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 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. 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

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

Primary outcomes:
measure: Number of participants of Dose Limiting Toxicity (DLT) with GAIA-102 (Phase I)
timeFrame: Cycle 1 (Cycle period is 28 days)
measure: Frequency and severity of adverse events(Phase I)
timeFrame: 2 year
measure: Progression Free Survival (PFS) rate at 6 months (Phase II)
timeFrame: Week 24
Secondary outcomes:
measure: Objective Response Rate （ORR) and Disease Control Rate (DCR)(Phase I)
timeFrame: Week 24
measure: Progression-free Survival(Phase I)
timeFrame: 2 year
measure: Overall Survival(Phase I)
timeFrame: 2 year
measure: Pharmacokinetics of GAIA-102(Phase I)
timeFrame: pre-dose
measure: Biomarker of GAIA-102(Phase I)
timeFrame: pre-dose
measure: Objective Response Rate Disease Control Rate(Phase II)
timeFrame: 2 year
measure: Progression-free Survival (Phase II)
timeFrame: 2 year
measure: Objective Response Period and Period until Objective Response (Phase II)
timeFrame: 2 year
measure: Overall Survival (Phase II)
timeFrame: 2 year
measure: Frequency and severity of adverse events (Phase II)
timeFrame: 2 year
measure: Biomarker of GAIA-102(Phase II)
timeFrame: pre-dose
Other outcomes:
Locations:
city: Fukuoka-shi
country: Japan
facility: Kyushu University Hospital
state: Fukuoka
Study officials:
References: