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)

Overview

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.

Interventions

• Biological Phase I part
  Administration of GAIA-102 as a monotherapy or GAIA-102 and pembrolizumab in combination.
• Biological Phase II part
  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.

Primary outcome measures

• Number of participants of Dose Limiting Toxicity (DLT) with GAIA-102 (Phase I) [Time frame: Cycle 1 (Cycle period is 28 days)]
• Frequency and severity of adverse events(Phase I) [Time frame: 2 year]
• Overall survival period in patients with gastric cancer (Phase II) [Time frame: up to 4 years]
• One-year survival rate in patients with pancreatic cancer (PhaseⅡ) [Time frame: 1 year]

Secondary outcome measures (12)

• Objective Response Rate （ORR) and Disease Control Rate (DCR)(Phase I) [Time frame: Week 24]
• Progression-free Survival(Phase I) [Time frame: 2 year]
• Overall Survival Period(Phase I) [Time frame: 2 year]
• Pharmacokinetics of GAIA-102(Phase I) [Time frame: pre-dose]
• Biomarker of GAIA-102(Phase I) [Time frame: pre-dose]
• Objective Response Rate Disease Control Rate(Phase II) [Time frame: up to 4 years]
• Progression-free Survival (Phase II) [Time frame: up to 4 years]
• Objective Response Period and Period until Objective Response (Phase II) [Time frame: up to 4 years]
• One-year survival rate in patients with gastric cancer (Phase II) [Time frame: 1 year]
• Overall survival period in patients with pancreatic cancer (Phase II) [Time frame: up to 4 years]
• Frequency and severity of adverse events (Phase II) [Time frame: up to 4 years]
• Biomarker of GAIA-102(Phase II) [Time frame: pre-dose]

Eligibility criteria

Inclusion criteria

• Unresectable or advanced recurrent gastric cancer with evident peritoneal dissemination on imaging, or with ascites, as well as unresectable or advanced recurrent pancreatic cancer.
• 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 and are refractory or intolerant to these therapies.

• 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 cancer with by histological or cytological examination
• 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
• 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
• 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)
• eGFR ≧30mL/min/1.73m2
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Japan · 1 center

• Kyushu University Hospital — Fukuoka

Identifiers

NCT: NCT05438459 · CTR024-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗