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

COordinated Nivolumab and IntraperiToneal IL-2 for Gastric CanceR With PeritOneaL Metastasis (CONTROL) Phase 1b Pilot Study

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.

Study Overview

• Status: Recruiting
• Conditions: Gastric Adenocarcinoma; Clinical Stage IV Gastric Cancer AJCC v8; Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Carcinoma; Metastatic Malignant Neoplasm in the Peritoneum
• Intervention / Treatment: Biological: Nivolumab; Procedure: Biopsy; Drug: Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin Calcium; Procedure: Computed Tomography; Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Biological: Aldesleukin; Procedure: Diagnostic Laparoscopy

Detailed 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) on study. Patients also receive standard of care nivolumab intravenously (IV), leucovorin calcium IV, fluorouracil IV, and oxaliplatin IV on study. 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.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Principal Investigator: Travis E. Grotz, M.D.
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 =< 15 days prior to registration)
• REGISTRATION: Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 15 days prior to registration)
• REGISTRATION: Platelet count >= 75,000/mm^3 (obtained =< 15 days prior to registration)
• REGISTRATION: Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 15 days prior to registration)
• REGISTRATION: Alanine aminotransferase (ALT) AND aspartate transaminase (AST) =< 1.5 x ULN (obtained =< 15 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 =< 15 days prior to registration)
• REGISTRATION: Calculated creatinine clearance >= 45 ml/min using the Cockcroft-Gault formula (obtained =< 15 days prior to registration)
• REGISTRATION: Negative pregnancy test done =< 7 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: Active malignancy currently receiving systemic treatment =< 6 months prior to registration
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (aldesleukin, nivolumab, chemotherapy); Patients receive aldesleukin IP on study. Patients also receive standard of care nivolumab IV, leucovorin calcium IV, fluorouracil IV, and oxaliplatin IV on study. Patients also undergo diagnostic laparoscopy with biopsy, PET/CT or PET/MRI, and collection of blood and tissue samples throughout the trial.

Biological: Nivolumab; Given IV; Other Names: BMS-936558; MDX-1106; NIVO; ONO-4538; Opdivo; CMAB819; Nivolumab Biosimilar CMAB819; Procedure: Biopsy; Undergo biopsy; Other Names: Bx; BIOPSY_TYPE; Drug: Fluorouracil; Given IV; Other Names: 5-Fluracil; Fluracil; 5 Fluorouracil; 5 Fluorouracilum; 5 FU; 5-Fluoro-2,4(1H, 3H)-pyrimidinedione; 5-Fluorouracil; 5-Fu; 5FU; AccuSite; Carac; Fluoro Uracil; Fluouracil; Flurablastin; Fluracedyl; Fluril; Fluroblastin; Ribofluor; Ro 2-9757; Ro-2-9757; Drug: Oxaliplatin; Given IV; Other Names: 1-OHP; Dacotin; Dacplat; Eloxatin; Ai Heng; Aiheng; Diaminocyclohexane Oxalatoplatinum; Eloxatine; JM-83; Oxalatoplatin; Oxalatoplatinum; RP 54780; RP-54780; SR-96669; Drug: Leucovorin Calcium; Given IV; Other Names: Wellcovorin; folinic acid; 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 Calcium Salt Pentahydrate; Folinoral; Folinvit; Foliplus; Folix; Imo; Lederfolat; Lederfolin; Leucosar; leucovorin; Rescufolin; Rescuvolin; Tonofolin; Procedure: Computed Tomography; Undergo PET/CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Procedure: Biospecimen Collection; Undergo collection of blood and tissue samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Magnetic Resonance Imaging; Undergo PET/MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Undergo PET/CT or PET/MRI; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Biological: Aldesleukin; Given IP; Other Names: Proleukin; 125-L-Serine-2-133-interleukin 2; r-serHuIL-2; Recombinant Human IL-2; Recombinant Human Interleukin-2; Procedure: Diagnostic Laparoscopy; Undergo diagnostic laparoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change of reduction in the peritoneal carcinomatosis index	About 90 days after last dose of aldesleukin (IL-2)
Incidence of adverse events	About 90 days after last dose of aldesleukin (IL-2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Summary statistics, including the median and other various timepoints will be reported as well as 95% confidence intervals.	From study entry to the first of either disease progression or death, assessed up to 3 years
Overall survival	Summary statistics, including the median and other various timepoints will be reported as well as 95% confidence intervals.	From date of study entry to date of death or last follow up, assessed up to 3 years
Histological response of the peritoneal metastasis	Will be assessed using the peritoneal regression grading score. Will be reported descriptively, including reporting of frequencies, percentages and 95% confidence intervals.	About 90 days after last dose of aldesleukin (IL-2)

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Travis E. Grotz, M.D., Mayo Clinic in Rochester

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2023
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: March 24, 2023
• First Submitted That Met QC Criteria: March 24, 2023
• First Posted (Actual): April 6, 2023

Study Record Updates

• Last Update Posted (Estimated): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Neoplasms; Stomach Neoplasms; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Immunological; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Immune Checkpoint Inhibitors; Antidotes; Vitamin B Complex; Hematinics; Aldesleukin; Fluorouracil; Oxaliplatin; Nivolumab; Leucovorin; Calcium; Levoleucovorin; Folic Acid; Calcium, Dietary; Interleukin-2
• Other Study ID Numbers: MC220404 (Other Identifier: Mayo Clinic); 22-009956 (Other Identifier: Mayo Clinic Institutional Review Board); NCI-2023-02250 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No