382 Participants Needed

Chemotherapy + Immunotherapy for Esophageal and Gastric Cancer

Recruiting at 774 trial locations
HP
AV
Overseen ByAishwarya Vijendran
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: Alliance for Clinical Trials in Oncology
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This phase III trial compares the effect of modified fluorouracil, leucovorin calcium, oxaliplatin, and irinotecan (mFOLFIRINOX) to modified fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX) for the treatment of advanced, unresectable, or metastatic HER2 negative esophageal, gastroesophageal junction, and gastric adenocarcinoma. The usual approach for patients is treatment with FOLFOX chemotherapy. Chemotherapy drugs 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. Fluorouracil stops cells from making DNA and it may kill tumor cells. Leucovorin is used with fluorouracil to enhance the effects of the drug. Oxaliplatin works by killing, stopping, or slowing the growth of tumor cells. Some patients also receive an immunotherapy drug, nivolumab, in addition to FOLFOX chemotherapy. Immunotherapy may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Irinotecan blocks certain enzymes needed for cell division and DNA repair, and it may kill tumor cells. Adding irinotecan to the FOLFOX regimen could shrink the cancer and extend the life of patients with advanced gastroesophageal cancers.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on medications like corticosteroids or other immunosuppressive drugs, you may need to adjust them as per the trial's requirements.

What data supports the effectiveness of the drug combination mFOLFIRINOX, FOLFIRINOX, mFOLFOX, Nivolumab, and Opdivo for esophageal and gastric cancer?

Research shows that modified FOLFOX6 (mFOLFOX6) has been effective as a second-line treatment for metastatic esophageal cancer, and combinations of 5-fluorouracil (5-FU) with other drugs have shown promise in treating gastrointestinal cancers, including esophageal and gastric cancers. Additionally, FOLFOX combined with radiotherapy has been effective for inoperable esophageal cancer.12345

Is the combination of chemotherapy and immunotherapy safe for treating esophageal and gastric cancer?

The modified FOLFIRINOX and FOLFOX regimens, which are similar to the treatment being considered, have been studied for other cancers like pancreatic and colorectal cancer. These treatments can cause side effects, such as low white blood cell counts and fever, but they are generally considered safe when managed properly.678910

How is the mFOLFIRINOX treatment different from other drugs for esophageal and gastric cancer?

The mFOLFIRINOX treatment combines chemotherapy with immunotherapy, which is unique because it uses a modified version of the FOLFIRINOX regimen, typically used for other cancers, to potentially enhance effectiveness in esophageal and gastric cancer. This approach may offer an alternative for patients who cannot tolerate standard oral treatments due to conditions like gastrointestinal obstructions.1341112

Eligibility Criteria

Adults with advanced, inoperable or metastatic HER2 negative esophageal, gastroesophageal junction, and gastric adenocarcinoma can join. They shouldn't have had previous treatment for their advanced cancer but may have had prior therapy if completed over a year ago. Participants need adequate organ function and no active autoimmune diseases requiring recent treatment. Those with certain heart conditions or infections like HIV must meet specific criteria.

Inclusion Criteria

Total bilirubin =< 1.5 x ULN
HIV positive patients meeting specific criteria
Measurable disease or non-measurable but evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
See 19 more

Exclusion Criteria

I am of childbearing age and have a negative pregnancy test.
No medical conditions making the protocol unreasonably hazardous
Not pregnant and not nursing
See 4 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive mFOLFIRINOX or mFOLFOX with nivolumab as clinically indicated, with MRI and CT scans throughout the trial

Up to 3 years
Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

  • mFOLFIRINOX
  • mFOLFOX
  • Nivolumab
Trial OverviewThe trial compares mFOLFIRINOX (a combination of chemotherapy drugs) to mFOLFOX (another chemo combo), both aiming to stop tumor growth by killing cells or preventing cell division. Some patients will also receive Nivolumab, an immunotherapy drug designed to boost the immune system's response against cancer cells.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm I (mFOLFIRINOX, nivolumab)Experimental Treatment9 Interventions
Patients receive fluorouracil IV, leucovorin calcium IV, oxaliplatin IV, and irinotecan IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.
Group II: Arm II (mFOLFOX, nivolumab)Active Control8 Interventions
Patients receive fluorouracil IV, leucovorin calcium IV, and oxaliplatin IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.

mFOLFIRINOX is already approved in European Union, United States, Canada for the following indications:

🇪🇺
Approved in European Union as mFOLFIRINOX for:
  • Pancreatic ductal adenocarcinoma (PDAC)
🇺🇸
Approved in United States as mFOLFIRINOX for:
  • Advanced pancreatic cancer
🇨🇦
Approved in Canada as mFOLFIRINOX for:
  • Resectable pancreatic ductal adenocarcinoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials
521
Recruited
224,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

In a study of 242 patients with metastatic esophagus cancer, 38.8% received second-line treatment with the modified FOLFOX6 (mFOLFOX6) regimen after failing cisplatin-plus-5-fluorouracil chemotherapy, showing an objective response rate of 41.4%.
While mFOLFOX6 was effective, with 6.3% achieving complete response and 35.1% achieving partial response, it also had a high incidence of grade 3/4 toxicity in 71.2% of patients, primarily due to hematologic issues.
Second-Line Modified FOLFOX6 Regimen in The Patients with Metastatic Esophagus Cancer.Koca, D., Ozdemir, O., Demir, D., et al.[2018]
5-Fluorouracil (5-FU) combined with folinic acid (FA) or alpha-interferon (IFN) has shown improved clinical activity in treating esophageal and gastric cancers compared to 5-FU alone, with 27% objective remissions reported in esophageal cancer.
In advanced gastric cancer, the combination of 5-FU/FA and 5-FU/IFN resulted in higher remission rates, with some studies reporting response rates exceeding 50% when combined with other chemotherapy agents.
Biochemical modulation of 5-fluorouracil by folinic acid or alpha-interferon with and without other cytostatic drugs in gastric, esophageal, and pancreatic cancer.Wilke, H., Stahl, M., Schmoll, HJ., et al.[2018]
In a study of 30 patients with resectable esophageal squamous cell carcinoma, a chemotherapy regimen combining 5-fluorouracil, cisplatin, and interferon-alpha showed promising results, with a median overall survival of 26.3 months.
The treatment led to a complete pathological response in 4 out of 23 patients who underwent esophagectomy, indicating significant effectiveness, although there was one toxic death due to esophageal perforation.
Phase II trial of neoadjuvant cisplatin, 5-fluorouracil and interferon-alpha in operable squamous cell carcinoma of the esophagus.Bazarbashi, S., Abdelsalam, M., Amin, T., et al.[2013]

References

Second-Line Modified FOLFOX6 Regimen in The Patients with Metastatic Esophagus Cancer. [2018]
Biochemical modulation of 5-fluorouracil by folinic acid or alpha-interferon with and without other cytostatic drugs in gastric, esophageal, and pancreatic cancer. [2018]
Phase II trial of neoadjuvant cisplatin, 5-fluorouracil and interferon-alpha in operable squamous cell carcinoma of the esophagus. [2013]
Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. [2022]
[A case of esophageal cancer associated with colon cancer successfully treated with combination chemotherapy of FOLFOX and concurrent radiotherapy]. [2013]
A phase II study of a modified FOLFOX6 regimen as neoadjuvant chemotherapy for locally advanced gastric cancer. [2022]
Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. [2023]
A Multicenter Clinical Phase II Study of FOLFOXIRI Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer: QUATTRO Study. [2022]
Efficacy and Safety of Modified FOLFOXIRI+α in the Treatment of Advanced and Recurrent Colorectal Cancer: A Single-center Experience. [2023]
Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer. [2022]
Impact of modified FOLFOX-6 for patients with gastric cancer and a gastrointestinal obstruction. [2020]
Modified 5-fluorouracil/leucovorin/irinotecan as a feasible and efficacious second-line chemotherapeutic regimen in advanced gastric cancers. [2022]