Immunotherapy + Chemotherapy for Stomach Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Mayo Clinic
Must be taking: FOLFOX, Nivolumab
Must not be taking: Corticosteroids, Immunosuppressants
Disqualifiers: Pregnancy, HIV, Autoimmune disease, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial requires participants to be on specific chemotherapy and immunotherapy drugs (FOLFOX and nivolumab) and does not allow certain prior therapies like IL-2, chronic corticosteroids, or immunosuppressive agents. Inhaled corticosteroids are allowed, but if you are on other medications, it's best to discuss with the trial team to see if they are permitted.
What data supports the effectiveness of the drug combination used in the Immunotherapy + Chemotherapy for Stomach Cancer trial?
Research shows that high levels of certain immune cells (tumor-infiltrating lymphocytes) in the tumor are linked to better outcomes in patients treated with FOLFOX, a chemotherapy regimen that includes some of the drugs in this trial. This suggests that the combination of these drugs may improve treatment effectiveness in stomach cancer.
12345Is the combination of immunotherapy and chemotherapy for stomach cancer safe?
Immunotherapy drugs like nivolumab, used in cancer treatment, can cause immune-related side effects such as diarrhea, colitis (inflammation of the colon), and other gastrointestinal issues. These side effects can range from mild to severe, and management often involves medications to suppress the immune response.
678910What makes the Immunotherapy + Chemotherapy treatment for stomach cancer unique?
This treatment combines immunotherapy (using drugs like Nivolumab, which helps the immune system attack cancer cells) with chemotherapy (using drugs like Fluorouracil and Oxaliplatin, which kill cancer cells directly), offering a novel approach that targets cancer in multiple ways. This combination is particularly promising because it leverages the body's immune response alongside traditional chemotherapy, potentially improving outcomes for patients with advanced gastric cancer.
134511Eligibility Criteria
Adults with confirmed gastric or gastroesophageal junction adenocarcinoma that has spread to the abdominal lining, who are in relatively good health (ECOG 0-2) and have not shown non-peritoneal metastasis. They must be able to provide blood and tissue samples, return for follow-up, and meet specific blood count and organ function criteria. Pregnant or nursing individuals, those unwilling to use contraception, or those with certain prior treatments or severe concurrent diseases cannot participate.Inclusion Criteria
Calculated creatinine clearance >= 45 ml/min using the Cockcroft-Gault formula (obtained =< 15 days prior to registration)
Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
My cancer is confirmed as stomach or GEJ adenocarcinoma.
+16 more
Exclusion Criteria
I have not had a heart attack in the last 6 months and don't need ongoing therapy for severe heart rhythm problems.
Nursing persons
My cancer has spread beyond the peritoneum, found during a laparoscopy.
+13 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive aldesleukin intraperitoneally, nivolumab intravenously, and standard chemotherapy drugs over 8 cycles, with diagnostic procedures and sample collections
16 weeks
8 cycles, each with multiple visits for treatment and assessments
Follow-up
Participants are monitored for safety and effectiveness after treatment completion, with follow-up visits at 30 days, 90 days, and every 3 months for up to 3 years
3 years
Regular follow-up visits at specified intervals
Participant Groups
The trial is testing aldesleukin combined with nivolumab (an immune system booster) alongside standard chemotherapy drugs fluorouracil, leucovorin calcium, and oxaliplatin. The goal is to see if this combination is more effective for patients whose stomach cancer has spread to the peritoneum compared to standard treatment alone.
1Treatment groups
Experimental Treatment
Group I: Treatment (aldesleukin, nivolumab, chemotherapy)Experimental Treatment11 Interventions
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.
Aldesleukin is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Proleukin for:
- Metastatic renal cell carcinoma
- Metastatic melanoma
🇪🇺 Approved in European Union as Proleukin for:
- Metastatic renal cell carcinoma
🇨🇦 Approved in Canada as Proleukin for:
- Metastatic renal cell carcinoma
- Metastatic melanoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mayo Clinic in RochesterRochester, MN
Loading ...
Who Is Running the Clinical Trial?
Mayo ClinicLead Sponsor
References
[Pre- and post-chemotherapy expressions of Th1 and Th2 type cytokines and their clinical significance in gastric cancer patients]. [2013]To investigate the pre- and post-chemotherapy expression levels of Th1 and Th2 type cytokines in peripheral blood CD4(+) T lymphocytes, the changes of Th1/Th2 ratio and their clinical significance in patients with gastric cancer.
High levels of tumor-infiltrating lymphocytes showed better clinical outcomes in FOLFOX-treated gastric cancer patients. [2021]Background: Tumor-infiltrating lymphocytes (TILs) and postoperative chemotherapeutics interact in the tumor micro-environment. This interaction has not been well investigated in gastric cancer. Materials & methods: A total of 129 patients were divided into high or low TILs based on the median number of positive CD3+ and FoxP3+ T cells, which was assessed by immunocytochemistry. Results: Cox regression analysis showed that the stage III disease with shorter overall survival was significant. The analysis showed that high numbers of CD3+ or FoxP3+ T cells have better clinical outcomes in FOLFOX-treated patients. Conclusion: High CD3+ and FoxP3+ T-cell infiltration was associated with better clinical outcomes in patients with gastric cancer treated with FOLFOX, suggesting TILs incorporated into algorithms to improve the therapeutic efficacy of optimal chemotherapy.
Chemotherapy of gastric cancer. [2019]Patients with gastric adenocarcinomas have a poor prognosis. Because curative surgery is often impossible (metastatic disease) or extremely difficult (locally advanced tumors), and the majority of patients undergoing curative resection relapse, chemotherapy has been actively studied in gastric cancer. Many drugs have shown activity; however, single-agent chemotherapy failed to demonstrate increased survival benefit. Several combination regimens have been developed with high activity in locally advanced and metastatic disease. Among them are 5-fluorouracil (5-FU) plus high dose methotrexate plus doxorubicin (FAMTX), etoposide plus doxorubicin plus cisplatin (EAP), etoposide plus leucovorin plus 5-FU (ELF), and epirubicin plus cisplatin plus 5-FU (ECF). Although the response rates of these schedules are encouraging, the toxicity is considerable. Randomized trials comparing chemotherapy with best supportive care showed an increase in overall survival and in quality-of-life. Up to now adjuvant chemotherapy in curatively resected gastric cancer patients has failed to improve survival as compared with surgical controls. Phase II trials with preoperative chemotherapy have shown very promising results, but results of randomized trials should be awaited to judge the real value of this approach. At this moment it cannot yet be estimated whether preoperative chemotherapy does positively influence the resection rate and survival of patients with clinically resectable tumors.
Histological complete response to a combined docetaxel/cisplatin/fluorouracil neoadjuvant chemotherapy for T4 stage gastric adenocarcinoma. [2021]Local advanced gastric carcinoma has a very poor prognosis. When a T4 gastric carcinoma has invaded the surrounding tissues and organs, curative resection is unlikely. We present here a case of a 63-year-old woman with a T4 unresectable gastric adenocarcinoma. She underwent two 3-week cycles of docetaxel/cisplatin/fluorouracil chemotherapy, followed by radical gastric resection. Each cycle consisted of 75 mg/m2 docetaxel and 75 mg/m2 cisplatin on day 1, and 200 mg/m2 leucovorin and 500 mg/m2 fluorouracil on days 1 through 5. The patient exhibited a complete histologic response. Our results indicate that docetaxel/cisplatin/fluorouracil neoadjuvant chemotherapy is a promising method of treatment for advanced gastric cancer.
[Influence of chemotherapy on Th1/Th2 cytokine switching in stomach cancer patients]. [2018]To observe the influence of chemotherapy on the switching of Th1/Th2 cytokines in stomach cancer patients.
Immune Checkpoint Inhibitor-Mediated Diarrhea and Colitis: A Clinical Review. [2021]Immune-mediated diarrhea and colitis (IMDC) is among the most common immune-related adverse events in patients with cancer treated with immune checkpoint inhibitors (ICIs). Many factors will affect the risk of IMDC, including the type of ICI used, the type of underlying cancer, and patient characteristics. A recent study showed that preexisting inflammatory bowel disease significantly increases the risk of diarrhea and colitis with ICI treatment. In terms of management, early endoscopic evaluation improves clinical outcome by identifying high-risk patients who will benefit from early add-on immunosuppressants. Inflammatory markers, including fecal lactoferrin and calprotectin, are good screening tools to predict which patients are at risk for colitis. Calprotectin especially is associated with colitis outcome and can be used as a surrogate marker to follow treatment response. Corticosteroids remain the first-line medical treatment of IMDC management, and add-on therapy with vedolizumab or infliximab should be considered in selected patients. Fecal microbiota transplantation may be considered in refractory cases. The decision to resume ICI should be decided by balancing the risk of recurrent IMDC and the likelihood of benefiting from further ICI treatment. There is no clear evidence about whether the use of immunosuppressants will result in a worse cancer outcome. With emerging evidence, our understanding and management strategies are likely to evolve in the future.
Immune Checkpoint Inhibitors-Induced Colitis. [2019]Immune checkpoint inhibitors (ICIs) have shown significant benefit in cancer patients, but are associated with immune-related adverse events (irAEs), that can affect the gastrointestinal tract resulting in diarrhea and colitis. IrAEs range from mild self-limiting to severe life-threatening disease, which potentially limit the use of these medications. Diagnosis of ICI-induced colitis is based on clinical symptoms, physical examination, stool tests, endoscopic evaluation, and/or imaging. Current management strategy is mainly anti-diarrheal agents for mild symptoms, and immunosuppressants (e.g., corticosteroids, and infliximab or vedolizumab) for more severe cases.
Nivolumab-Induced Concomitant Severe Upper and Lower Gastrointestinal Immune-Related Adverse Effects. [2020]Immunotherapy agents such as cytotoxic T-lymphocyte antigen-4 and programed cell death protein-1 inhibitors show efficacy in cancer therapy but are associated with immune-related adverse events. It commonly presents as diarrhea but can cause colitis, mimicking inflammatory bowel disease. Our patient is a 78-year-old man on nivolumab therapy for metastatic lung cancer who developed new onset nausea and diarrhea. Endoscopy revealed inflammation of the upper and lower gastrointestinal tract, and histology revealed transmural colon and gastric inflammation. We present a fascinating case of severe concomitant aphthous ulcers, esophagitis, gastritis, and enterocolitis.
Treatment of Immune Checkpoint Inhibitor Induced Colitis with Infliximab. [2020]Several immunotherapeutic agents function against the T cell immune checkpoint inhibitor pathways thereby reestablishing immune response to elusive malignancies. Namely, the programmed death-1 co-receptor (PD-1) or ligand (PD-L1) and cytotoxic T lymphocyte- associated protein 4 (CTLA-4) are well known checkpoint targets of current FDA approved drugs. Among these drugs nivolumab, an IgG4 anti-PD-1 antibody, and ipilimumab, an anti-CTLA-4 antibody, are used to treat numerous malignancies but carry a large list of potential side effects termed immune-related adverse effects (irAEs). We describe the presentation, clinical course, and resolution of steroid-resistant immune checkpoint inhibitor-induced colitis secondary to administration of these two drugs in a 66-year-old female patient treated with infliximab.
Possible atezolizumab-associated acute kidney injury and immune thrombocytopenia. [2022]The immune checkpoint inhibitors (ICIs), which are used to activate the immune system and stimulate anti-tumor activity, are preferred in many cancers. Atezolizumab acts by blocking programmed cell death ligand (PD-L1) and may cause immune hyperstimulation in healthy tissues like other ICIs, resulting in immune-related adverse events (irAEs). Hepatitis, colitis, pneumonitis, hypophysitis, hypothyroidism, rash, musculoskeletal problems are the most common irAEs, and on the other hand, acute kidney injury (AKI) and immune thrombocytopenic purpura (ITP) are infrequent.
Toripalimab combined with targeted therapy and chemotherapy achieves pathologic complete response in gastric carcinoma: A case report. [2022]Neoadjuvant or perioperative chemotherapy combined with surgery can reduce postoperative recurrence and improve the long-term survival rate of patients with locally advanced resectable gastric carcinoma. Nivolumab combined with chemotherapy has been recommended by the National Comprehensive Cancer Network guidelines as a first-line therapy for advanced gastric carcinoma/ adenocarcinoma of the gastroesophageal junction and serves as the basis for immunotherapy combined with chemotherapy to become a neoadjuvant therapy. Herein, we report a case in which pathologic complete response was achieved by neoadjuvant administration of toripalimab, Herceptin, and docetaxel, oxaliplatin, calcium folinate, and fluorouracil (FLOT) chemotherapy followed by surgery for human epidermal growth factor receptor 2 (HER2)- and programmed death-ligand 1 (PD-L1)-positive locally advanced gastric carcinoma. We hope that this case will shed some light on neoadjuvant therapy for gastric carcinoma.