Aldesleukin With Nivolumab and Standard Chemotherapy for Treatment of Gastric Cancer With Peritoneal Metastasis

Mayo Clinic

Status and phase

Enrolling

Phase 1

Conditions

Clinical Stage IV Gastric Cancer AJCC v8

Metastatic Malignant Neoplasm in the Peritoneum

Metastatic Gastric Carcinoma

Gastroesophageal Junction Adenocarcinoma

Gastric Adenocarcinoma

Treatments

Procedure: Computed Tomography

Procedure: Biopsy

Procedure: Positron Emission Tomography

Biological: Nivolumab

Procedure: Magnetic Resonance Imaging

Drug: Fluorouracil

Drug: Leucovorin Calcium

Drug: Oxaliplatin

Procedure: Biospecimen Collection

Procedure: Diagnostic Laparoscopy

Biological: Aldesleukin

Study type

Interventional

Funder types

Other

Identifiers

NCT05802056

MC220404

NCI-2023-02250 (Registry Identifier)

22-009956 (Other Identifier)

Details and patient eligibility

About

This phase Ib trial test effects of aldesleukin in combination with nivolumab and standard chemotherapy in treating patients with gastric cancer that has spread to the tissue lining of the abdomen (peritoneal metastasis). Aldesleukin is similar to a protein that naturally exists in the body that stimulates the immune system to fight infections. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as leucovorin calcium, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving aldesleukin in combination with nivolumab and standard chemotherapy may work better in treating patients with gastric cancer with peritoneal metastasis.

Full description

PRIMARY OBJECTIVE:

I. To evaluate the reduction in the peritoneal carcinomatosis index (PCI) after completion of the study treatment.

SECONDARY OBJECTIVES:

I. Evaluate histological response of the peritoneal metastasis to study treatment using the peritoneal regression grading score (PRGS).

II. Assess overall survival (OS). III. Assess progression-free survival (PFS). IV. Assess safety and tolerability of the study regimen.

TERTIARY AND CORRELATIVE RESEARCH OBJECTIVES:

I. Assess the number and percentage of patients that successfully undergo complete cytoreductive surgery after treatment.

II. Evaluate for helper T cell, cytotoxic T cell, natural killer (NK) cells as well as T-reg cells in blood and peritoneal fluid.

III. Evaluate the neutrophilic, lymphocytic, and eosinophilic infiltration of tumor using a standardized classification.

OUTLINE:

Patients receive aldesleukin intraperitoneally (IP) over at least 40 minutes on days 1 and 8 of each cycle. Patients also receive standard of care nivolumab intravenously (IV) over 30 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, oxaliplatin IV over 2 hours on day 1, and flurouracil IV continuously over 46 hours on days 1-3 for each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo diagnostic laparoscopy with biopsy, positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance imaging (MRI), and collection of blood and tissue samples throughout the trial.

After completion of study treatment, patients follow up at 30 days, 90 days then every 3 months for up to 3 years.

Enrollment

15 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

PRE-REGISTRATION: Age >= 18 years
PRE-REGISTRATION: Disease characteristics
- Histological confirmation of adenocarcinoma of the stomach or gastroesophageal junction (GEJ)
- Currently receiving first-line therapy with leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) and nivolumab without evidence of disease progression OR planning to start first-line therapy with FOLFOX and nivolumab
PRE-REGISTRATION: No radiographic or histological evidence of non-peritoneal metastasis
PRE-REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
PRE-REGISTRATION: Willingness to provide mandatory blood specimens for correlative research
PRE-REGISTRATION: Willingness to provide mandatory tissue specimens for correlative research
PRE-REGISTRATION: Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
REGISTRATION: Peritoneal Carcinomatosis Index (PCI) >= 1 and =< 24 obtained =< 30 days prior to registration
REGISTRATION: Clinical, pathological, or radiographic evidence of peritoneal metastasis per PCI and Peritoneal Regression Grading Score (PRGS)
REGISTRATION: Hemoglobin >= 8.0 g/dL (obtained =< 30 days prior to registration)
REGISTRATION: Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 30 days prior to registration)
REGISTRATION: Platelet count >= 75,000/mm^3 (obtained =< 30 days prior to registration)
REGISTRATION: Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 30 days prior to registration)
REGISTRATION: Alanine aminotransferase (ALT) AND aspartate transaminase (AST) =< 1.5 x ULN (obtained =< 30 days prior to registration)
REGISTRATION: Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) =< 1.5 x ULN OR if patient is receiving anticoagulant therapy, then INR or aPTT is within target range of therapy (obtained =< 30 days prior to registration)
REGISTRATION: Calculated creatinine clearance >= 40 ml/min using the Cockcroft-Gault formula (obtained =< 30 days prior to registration)
REGISTRATION: Negative pregnancy test done =< 8 days prior to registration, for persons of childbearing potential only
REGISTRATION: Provide written informed consent
REGISTRATION: Willingness to provide mandatory blood specimens for correlative research
REGISTRATION: Willingness to provide mandatory tissue specimens for correlative research
REGISTRATION: Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

Exclusion criteria

PRE-REGISTRATION: Any of the following because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects:
- Pregnant persons
- Nursing persons
- Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception
PRE-REGISTRATION: Any of the following prior therapies: IL-2 or chronic corticosteroids, or immunosuppressive agents
- NOTE: Inhaled corticosteroids are allowed
PRE-REGISTRATION: Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
PRE-REGISTRATION: Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
PRE-REGISTRATION: Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Or psychiatric illness/social situations that would limit compliance with study requirements
- Autoimmune disease
PRE-REGISTRATION: Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
PRE-REGISTRATION: Active second malignancy currently receiving systemic treatment =< 6 months prior to pre-registration
PRE-REGISTRATION: History of myocardial infarction =< 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
REGISTRATION: Identification of non-peritoneal metastasis during laparoscopy
REGISTRATION: Any of the following because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects:
- Pregnant persons
- Nursing persons
- Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception
REGISTRATION: Any of the following therapies: prior immune checkpoint inhibitors, prior IL-2, or chronic corticosteroids or immunosuppressive agents
- NOTE: Inhaled corticosteroids are allowed. One-time antiemetic dose is allowed
REGISTRATION: Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
REGISTRATION: Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy
REGISTRATION: Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Or psychiatric illness/social situations (e.g., substance abuse) that would limit compliance with study requirements
- Autoimmune disease requiring systemic treatment
- Small bowel obstruction
REGISTRATION: Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
REGISTRATION: History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
REGISTRATION: Small bowel obstruction < 15 days prior to registration

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

15 participants in 1 patient group

Treatment (aldesleukin, nivolumab, chemotherapy)

Experimental group

Description:

Patients receive aldesleukin IP over at least 40 minutes on days 1 and 8 of each cycle. Patients also receive standard of care nivolumab IV over 30 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, oxaliplatin IV over 2 hours on day 1, and flurouracil IV continuously over 46 hours on days 1-3 for each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo diagnostic laparoscopy with biopsy, PET/CT or PET/MRI, and collection of blood and tissue samples throughout the trial.

Treatment: