sFOLFOXIRI for Gastroesophageal Cancer

Recruiting at 6 trial locations

Overseen By Patrick Boland, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Brain metastases, Active malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 28 days per cycle

38 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective is to determine the clinical efficacy of treatment regimen in terms of objective response rate (ORR). The secondary objectives is to determine the clinical efficacy of the study treatment in terms of progression free survival (PFS) and overall survival (OS). Additionally, to characterize the safety and toxicity profile of the study treatment as measured by the adverse event rates.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

What data supports the effectiveness of the treatment sFOLFOXIRI for gastroesophageal cancer?

The combination treatment FOLFIRINOX, which is similar to sFOLFOXIRI, has shown effectiveness as a first-line therapy for other gastrointestinal cancers like pancreatic and colon cancers. This suggests potential benefits for gastroesophageal cancer as well. ^{1 2 3 4 5}

Is sFOLFOXIRI generally safe for humans?

The safety data for treatments similar to sFOLFOXIRI, like FOLFOXIRI and FOLFIRI, show that they can cause serious side effects such as neutropenia (low white blood cell count) and diarrhea. In some studies, a significant number of patients experienced severe side effects, but these treatments are generally considered to have an acceptable safety profile for advanced cancers. ^{6 7 8 9 10}

How is the drug sFOLFOXIRI different from other treatments for gastroesophageal cancer?

sFOLFOXIRI is unique because it combines multiple chemotherapy agents (leucovorin, fluorouracil, irinotecan, and oxaliplatin) into one regimen, which has shown effectiveness in treating other gastrointestinal cancers like pancreatic and colon cancers. This combination may offer a new option for gastroesophageal cancer, where standard treatments have limited response rates. ^{1 2 11 12 13}

Research Team

Patrick M. Boland

Principal Investigator

Rutgers Cancer Institute of New Jersey

Eligibility Criteria

Adults with advanced gastroesophageal cancer that's HER2 negative and hasn't spread to the brain can join. They should be relatively fit (ECOG PS 0-2), have measurable disease, no recent major surgery or other cancers, and not be on high-dose steroids. No prior treatment for metastatic cancer is allowed except some mFOLFOX6 cycles.

Inclusion Criteria

I agree to use birth control or abstain from sex during the study.

Measurable disease by response evaluation criteria in solid tumors (RECIST) v1.1

Ability to understand the nature of this study protocol and give written informed consent

Exclusion Criteria

I have an autoimmune disease that hasn't needed strong medication in the last 2 years.

I am not currently taking steroids equivalent to 10 mg/day of prednisone.

I haven't had any other cancers in the last 3 years that could affect my treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a four-week alternating FOLFOX and FOLFIRI (sFOLFOXIRI) regimen, with optional nivolumab

28 days per cycle

Visits on days 1 and 15 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• sFOLFOXIRI

Trial Overview The trial tests sFOLFOXIRI, a combination of chemotherapy drugs given in four-week cycles, to see how well it works against advanced gastroesophageal cancer by measuring tumor response rate, progression-free survival time, and overall survival time.

Participant Groups

Group I: 4week alternating FOLFOX and a combination chemotherapy regime FOLFIRI (sFOLFOXIRI), Experimental Treatment 1 Intervention

A cycle will constitute 28 days of treatment, which will consist of one chemotherapy combination, either FOLFOX or FOLFIRI as below: 1. Odd Cycles (e.g. 1, 3, 5, etc...) - mFOLFOX6 initiated on days 1 \& 15: (Oxaliplatin 85 mg/m2 IV, leucovorin 400 mg/m2, 5FU 400 mg/m2 bolus, then 5FU 2400 mg/m2 over 46 hours) 2. Even Cycles (e.g. 2,4,6, etc...) - FOLFIRI initiated on days 1 \& 15: (Irinotecan 180 mg/m2 IV, leucovorin 400 mg/m2, 5FU 400 mg/m2 bolus, then 5FU 2400 mg/m2 over 46 hours) 3. Nivolumab (optional, in-line with labelled approval) - 240 mg every 2 weeks

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

Approved in European Union as FOLFOXIRI for:

• Advanced or metastatic bowel cancer

Approved in United States as FOLFOXIRI for:

• Metastatic colorectal cancer

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Findings from Research

In a phase 2 study involving 67 patients with advanced gastroesophageal adenocarcinoma, the FOLFIRINOX regimen demonstrated a high objective response rate (ORR) of 61% for ERBB2-negative patients and 85% for ERBB2-positive patients, indicating its efficacy as a first-line treatment.

The treatment was associated with manageable side effects, with common toxicities including neutropenia and diarrhea, but no unexpected adverse effects, suggesting that FOLFIRINOX could be a safe and effective option for patients with good performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX for the Treatment of Advanced Gastroesophageal Cancers: A Phase 2 Nonrandomized Clinical Trial. Park, H., Jin, RU., Wang-Gillam, A., et al.[2021]

Reduced-intensity FOLFOXIRI (RI-FOLFOXIRI) was found to be an effective salvage chemotherapy for patients with refractory metastatic colorectal cancer (mCRC), with 15.6% of patients showing a partial response and 33.3% achieving stable disease.

Patients with wild-type K-RAS had a significantly longer overall survival (8.5 months) compared to those with mutant K-RAS (7.0 months), indicating that K-RAS status may influence treatment outcomes, while the most common side effects were neutropenia and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced-intensity FOLFOXIRI in Treating Refractory Metastatic Colorectal Cancer: A Pilot Study. Chen, HM., Lin, JK., Chen, WS., et al.[2017]

In a network meta-analysis of 10 randomized controlled trials involving 2,506 patients, the combination of FOLFOXIRI and targeted therapy significantly improved progression-free survival (PFS) and overall survival (OS) compared to FOLFOX/FOLFIRI with targeted therapy, indicating it may be a more effective first-line treatment for metastatic colorectal cancer (mCRC).

The study found that FOLFOXIRI plus targeted therapy did not increase toxicity levels compared to FOLFOX/FOLFIRI plus targeted therapy, suggesting that patients can benefit from improved outcomes without a higher risk of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is FOLFOXIRI alone or combined with targeted therapy administered as first-line treatment a reasonable choice for most patients with mCRC? Systematic review and network meta-analysis. Zhou, M., Yu, P., Hernick Davin, DB., et al.[2019]

In a clinical trial involving 142 patients with advanced esophageal squamous cell cancer, adding panitumumab to cisplatin and 5-fluorouracil (CFP) did not improve overall survival compared to CF alone, with median survival times of 10.2 months for CF versus 9.4 months for CFP.

The trial was stopped early due to interim results showing that patients receiving CFP had a higher risk of death related to disease progression, and more serious adverse events were reported in the CFP group, indicating that the addition of EGFR inhibition may not be beneficial in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER). Moehler, M., Maderer, A., Thuss-Patience, PC., et al.[2022]

The combination of docetaxel, 5-fluorouracil, and cisplatin (DFC) shows promise as a second-line chemotherapy for patients with metastatic esophageal cancer who are resistant to cisplatin, with a median overall survival of 8 months based on a study of 20 patients.

While DFC treatment resulted in a complete response in 1 patient and partial responses in 6 others, it also led to significant myelosuppression, with 65% of patients experiencing severe neutropenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-line combination chemotherapy with docetaxel for cisplatin-pretreated refractory metastatic esophageal cancer: a preliminary report of initial experience. Tanaka, T., Fujita, H., Sueyoshi, S., et al.[2018]

In a safety run-in phase of the DURIGAST PRODIGE 59 study involving 11 patients with advanced gastric or gastro-oesophageal junction adenocarcinoma, 63.6% experienced significant adverse events, primarily neutropenia, indicating a notable safety concern with the treatment combination.

The combination of FOLFIRI with Durvalumab and/or Tremelimumab showed an expected safety profile, allowing progression to the randomized phase II study, although careful monitoring for serious adverse events is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of FOLFIRI + Durvalumab +/- Tremelimumab in Second Line of Patients with Advanced Gastric Cancer: A Safety Run-In from the Randomized Phase II Study DURIGAST PRODIGE 59. Evrard, C., Aparicio, T., Soularue, E., et al.[2022]

In a phase II study involving 48 patients with metastatic gastric cancer, the modified FOLFOXIRI chemotherapy regimen demonstrated a high overall response rate of 66.7%, indicating significant antitumor activity.

The treatment was generally well tolerated, with manageable side effects; however, some patients experienced grade 3/4 toxicities, including neutropenia (12%) and diarrhea (10%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of irinotecan plus oxaliplatin and 5-fluorouracil/leucovorin in patients with untreated metastatic gastric adenocarcinoma. Lee, J., Kang, WK., Kwon, JM., et al.[2022]

In a study of 69 Asian patients with metastatic colorectal cancer, the combination of FOLFOXIRI and bevacizumab resulted in a high progression-free survival (PFS) rate of 75.2% at 10 months, indicating its effectiveness as a first-line treatment.

However, this regimen was associated with significant adverse events, particularly high rates of neutropenia (72.5%) and hypertension (34.8%), highlighting the need for careful monitoring, especially in patients with specific UGT1A1 genetic polymorphisms that increase the risk of severe neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicenter Clinical Phase II Study of FOLFOXIRI Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer: QUATTRO Study. Oki, E., Kato, T., Bando, H., et al.[2022]

In a pilot study of 29 patients with advanced esophageal or junctional adenocarcinoma, the FOLFIRI chemotherapy regimen showed a 31% objective response rate, with 2 complete responses and 7 partial responses, indicating significant efficacy.

The treatment had an acceptable safety profile, with manageable side effects; however, one patient experienced chemotherapy-related diarrhea leading to death, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRI chemotherapy in patients with advanced non resectable esophageal or junctional adenocarcinoma: a pilot study. Ferte, C., Romano, O., Mariette, C., et al.[2013]

In a study involving 249 patients with metastatic KRAS mutant colorectal carcinoma, the addition of simtuzumab to the chemotherapy regimen FOLFIRI did not improve clinical outcomes such as progression-free survival or overall survival compared to placebo.

The safety profile of simtuzumab was comparable to that of the placebo group, indicating that while it was tolerable, it did not enhance the effectiveness of the chemotherapy treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab in Combination with FOLFIRI for the Second-Line Treatment of Metastatic KRAS Mutant Colorectal Adenocarcinoma. Hecht, JR., Benson, AB., Vyushkov, D., et al.[2022]

A patient with esophageal cancer and colon cancer was treated with a modified FOLFOX6 chemotherapy regimen combined with radiotherapy, resulting in a partial response of the esophageal tumor and effective control of the disease.

Despite experiencing grade 3 leukopenia, the modified FOLFOX6 regimen was generally well tolerated, suggesting it could be a viable treatment option for inoperable esophageal cancer, warranting further clinical trials in Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A case of esophageal cancer associated with colon cancer successfully treated with combination chemotherapy of FOLFOX and concurrent radiotherapy]. Watanabe, Y., Tsutsui, M., Takeda, S., et al.[2013]

In a study of 28 patients with unresectable or recurrent esophageal squamous cell carcinoma (ESCC), the combination of S-1 and paclitaxel (S1/PTX) showed a response rate of 14.8%, with a median overall survival time of 306 days, indicating some clinical efficacy in this difficult-to-treat population.

While S1/PTX was generally well-tolerated, severe neutropenia occurred in 13 patients, highlighting the need for monitoring blood counts during treatment, although most non-hematological side effects were mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Trial of S-1 and Paclitaxel in Unresectable or Postoperative Recurrent Esophageal Squamous Cell Carcinoma Pretreated by Fluorouracil, Cisplatin, and Docetaxel Chemotherapy. Nakajima, Y., Kawada, K., Tokairin, Y., et al.[2019]

A 64-year-old man with advanced gastroesophageal junction adenocarcinoma and liver metastases achieved long-term survival and complete response of liver metastases after treatment with ramucirumab combined with paclitaxel in the RAINBOW trial.

The patient's complete metabolic response was confirmed through imaging scans over a period of several years, highlighting the potential efficacy of ramucirumab in treating advanced cancer after previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Survival in Gastroesophageal Junction Adenocarcinoma: Ramucirumab. Gil-Delgado, MA., Lucidarme, O., Bachet, JB., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

FOLFIRINOX for the Treatment of Advanced Gastroesophageal Cancers: A Phase 2 Nonrandomized Clinical Trial. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Reduced-intensity FOLFOXIRI in Treating Refractory Metastatic Colorectal Cancer: A Pilot Study. [2017]

3. United States pubmed.ncbi.nlm.nih.gov

Is FOLFOXIRI alone or combined with targeted therapy administered as first-line treatment a reasonable choice for most patients with mCRC? Systematic review and network meta-analysis. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER). [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Second-line combination chemotherapy with docetaxel for cisplatin-pretreated refractory metastatic esophageal cancer: a preliminary report of initial experience. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety of FOLFIRI + Durvalumab +/- Tremelimumab in Second Line of Patients with Advanced Gastric Cancer: A Safety Run-In from the Randomized Phase II Study DURIGAST PRODIGE 59. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Phase II trial of irinotecan plus oxaliplatin and 5-fluorouracil/leucovorin in patients with untreated metastatic gastric adenocarcinoma. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

A Multicenter Clinical Phase II Study of FOLFOXIRI Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer: QUATTRO Study. [2022]

9. England pubmed.ncbi.nlm.nih.gov

FOLFIRI chemotherapy in patients with advanced non resectable esophageal or junctional adenocarcinoma: a pilot study. [2013]

10. England pubmed.ncbi.nlm.nih.gov

A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab in Combination with FOLFIRI for the Second-Line Treatment of Metastatic KRAS Mutant Colorectal Adenocarcinoma. [2022]

11. Japan pubmed.ncbi.nlm.nih.gov

[A case of esophageal cancer associated with colon cancer successfully treated with combination chemotherapy of FOLFOX and concurrent radiotherapy]. [2013]

12. Switzerland pubmed.ncbi.nlm.nih.gov

A Pilot Trial of S-1 and Paclitaxel in Unresectable or Postoperative Recurrent Esophageal Squamous Cell Carcinoma Pretreated by Fluorouracil, Cisplatin, and Docetaxel Chemotherapy. [2019]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Long-Term Survival in Gastroesophageal Junction Adenocarcinoma: Ramucirumab. [2020]