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

NCT ID: NCT05802056

Last Updated: 2024-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-29

Study Completion Date

2026-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Clinical Stage IV Gastric Cancer AJCC V8 Gastric Adenocarcinoma Gastroesophageal Junction Adenocarcinoma Metastatic Gastric Carcinoma Metastatic Malignant Neoplasm in the Peritoneum

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (aldesleukin, nivolumab, chemotherapy)

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.

Group Type EXPERIMENTAL

Aldesleukin

Intervention Type BIOLOGICAL

Given IP

Biopsy

Intervention Type PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood and tissue samples

Computed Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Diagnostic Laparoscopy

Intervention Type PROCEDURE

Undergo diagnostic laparoscopy

Fluorouracil

Intervention Type DRUG

Given IV

Leucovorin Calcium

Intervention Type DRUG

Given IV

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo PET/MRI

Nivolumab

Intervention Type BIOLOGICAL

Given IV

Oxaliplatin

Intervention Type DRUG

Given IV

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT or PET/MRI

Interventions

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Aldesleukin

Given IP

Intervention Type BIOLOGICAL

Biopsy

Undergo biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo collection of blood and tissue samples

Intervention Type PROCEDURE

Computed Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Diagnostic Laparoscopy

Undergo diagnostic laparoscopy

Intervention Type PROCEDURE

Fluorouracil

Given IV

Intervention Type DRUG

Leucovorin Calcium

Given IV

Intervention Type DRUG

Magnetic Resonance Imaging

Undergo PET/MRI

Intervention Type PROCEDURE

Nivolumab

Given IV

Intervention Type BIOLOGICAL

Oxaliplatin

Given IV

Intervention Type DRUG

Positron Emission Tomography

Undergo PET/CT or PET/MRI

Intervention Type PROCEDURE

Other Intervention Names

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125-L-Serine-2-133-interleukin 2 Proleukin r-serHuIL-2 Recombinant Human IL-2 Recombinant Human Interleukin-2 BIOPSY_TYPE Bx Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized Tomography CT CT Scan tomography Computerized axial tomography (procedure) Computerized Tomography (CT) scan 5 Fluorouracil 5 Fluorouracilum 5 FU 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fluracil 5-Fu 5FU AccuSite Carac Fluoro Uracil Fluouracil Flurablastin Fluracedyl Fluracil Fluril Fluroblastin Ribofluor Ro 2-9757 Ro-2-9757 Adinepar Calcifolin Calcium (6S)-Folinate Calcium Folinate Calcium Leucovorin Calfolex Calinat Cehafolin Citofolin Citrec Citrovorum Factor Cromatonbic Folinico Dalisol Disintox Divical Ecofol Emovis Factor, Citrovorum Flynoken A Folaren Folaxin FOLI-cell Foliben Folidan Folidar Folinac Folinate Calcium folinic acid Folinic Acid Calcium Salt Pentahydrate Folinoral Folinvit Foliplus Folix Imo Lederfolat Lederfolin Leucosar leucovorin Rescufolin Rescuvolin Tonofolin Wellcovorin Magnetic Resonance Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan NMR Imaging NMRI Nuclear Magnetic Resonance Imaging Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) MRIs sMRI Structural MRI BMS-936558 CMAB819 MDX-1106 NIVO Nivolumab Biosimilar CMAB819 ONO-4538 Opdivo ABP 206 BCD-263 Nivolumab Biosimilar ABP 206 Nivolumab Biosimilar BCD-263 1-OHP Ai Heng Aiheng Dacotin Dacplat Diaminocyclohexane Oxalatoplatinum Eloxatin Eloxatine JM-83 Oxalatoplatin Oxalatoplatinum RP 54780 RP-54780 SR-96669 Medical Imaging, Positron Emission Tomography PET PET Scan Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging PT Positron emission tomography (procedure)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Travis E. Grotz, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic in Rochester

Locations

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Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Clinical Trials Referral Office

Role: CONTACT

Phone: 855-776-0015

Email: [email protected]

Facility Contacts

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Clinical Trials Referral Office

Role: primary

Travis E. Grotz, MD

Role: backup

Related Links

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Other Identifiers

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NCI-2023-02250

Identifier Type: REGISTRY

Identifier Source: secondary_id

MC220404

Identifier Type: OTHER

Identifier Source: secondary_id

22-009956

Identifier Type: OTHER

Identifier Source: secondary_id

MC220404

Identifier Type: -

Identifier Source: org_study_id