sFOLFOXIRI for Gastroesophageal Cancer
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Rutgers, The State University of New Jersey
Must not be taking: Corticosteroids, Immunosuppressants
Disqualifiers: Brain metastases, Active malignancy, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 3 Jurisdictions
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.
12345Is 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.
678910How 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.
12111213Eligibility 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
+14 more
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.
+10 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: 4week alternating FOLFOX and a combination chemotherapy regime FOLFIRI (sFOLFOXIRI),Experimental Treatment1 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, Australia for the following indications:
๐ช๐บ Approved in European Union as FOLFOXIRI for:
- Advanced or metastatic bowel cancer
๐บ๐ธ Approved in United States as FOLFOXIRI for:
- Metastatic colorectal cancer
๐ฆ๐บ Approved in Australia as FOLFOXIRI for:
- Metastatic colorectal cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Rutgers Cancer Institute of New JerseyNew Brunswick, NJ
RWJBarnabas Health - Robert Wood Johnson University HospitalHamilton, NJ
RWJBarnabas Health - Community Medical CenterToms River, NJ
RWJBarnabas Health - Newark Beth Israel Medical CenterNewark, NJ
More Trial Locations
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Who Is Running the Clinical Trial?
Rutgers, The State University of New JerseyLead Sponsor
References
FOLFIRINOX for the Treatment of Advanced Gastroesophageal Cancers: A Phase 2 Nonrandomized Clinical Trial. [2021]Standard first-line regimens for patients with metastatic gastroesophageal adenocarcinomas have an approximate 40% objective response rate (ORR). The combination of leucovorin, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) has been efficacious as first-line therapy for other gastrointestinal cancers, such as pancreatic and colon cancers.
Reduced-intensity FOLFOXIRI in Treating Refractory Metastatic Colorectal Cancer: A Pilot Study. [2017]To report on the efficacy and safety of reduced-intensity FOLFOXIRI (RI-FOLFOXIRI) as salvage chemotherapy for patients with refractory metastatic colorectal cancer (mCRC).
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]Whether the intensive administration of folinic acid, 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) alone or combined with target therapy as first-line treatment could improve the prognosis of metastatic colorectal cancer (mCRC) patients is controversial. PubMed, the Cochrane Collaboration Central Register of Controlled Clinical Trials, Cochrane Systematic Reviews, ClinicalTrials.gov, the databases of conferences were queried to identify RCTs evaluating the efficacies and toxicities of intensive therapies used for first-line treatment of mCRC patients. The search included articles dated from the inception of these resources until March 31, 2017. We estimated HRs for OS and PFS and RRs for ORR, the R0 resection rate, and toxicities. Ten RCTs comprising 2,506 patients were included in this network meta-analysis. The PFS of patients administered FOLFOXIRI plus target therapy experienced prolonged PFS and OS and improved ORRs compared with FOLFOX/FOLFIRI plus target therapy (PFS: HR 0.71, 95% CI 0.59-0.86; OS: HR 0.81, 95% CI 0.69-0.94; ORR: RR 1.66, 95% CI 0.96-2.88; R0 resection rate: RR 2.66, 95% CI 1.86-3.82). There were no significant differences between PFS, OS, ORRs, or R0 resection rates and toxicities of patients administered FOLFOXIRI and FOLFOX/FOLFIRI plus target therapy. Further, FOLFOXIRI plus target therapy did not increase toxicities compared with FOLFOX/FOLFIRI plus target therapy. FOLFOXIRI plus target therapy when administered as first-line treatment of patients with mCRC is the best choice and did not increase toxicities. The patients with RAS/BRAF mutations could benefit from FOLFOXIRI plus Bev. FOLFOXIRI is as effective as FOLFOX/FOLFIRI plus target therapy.
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]Palliative chemotherapy of advanced oesophageal squamous cell cancer (ESCC) consists of cisplatin/5-fluorouracil (CF) to target epidermal growth factor receptor (EGFR) with panitumumab (P); chemotherapy enhanced overall survival (OS) in advanced colorectal or squamous cell head and neck cancers. With prospective serum and tumour biomarkers, we tested if P added to CF (CFP) improved OS in advanced ESCC.
Second-line combination chemotherapy with docetaxel for cisplatin-pretreated refractory metastatic esophageal cancer: a preliminary report of initial experience. [2018]Patients with esophageal cancer often develop metastatic disease after esophageal resection and generally receive cisplatin-based chemotherapy or chemoradiotherapy. The efficacy and toxicity of the combination of docetaxel, 5-fluorouracil (5-FU) and cisplatin (DFC) as a second-line chemotherapy were evaluated in patients with postoperative metastatic esophageal cancer refractory to cisplatin-based chemotherapy.
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]Efficacy of immune checkpoint inhibitors (ICI) as monotherapy in 2nd line treatment for gastric or gastro-oesophageal junction (GEJ) adenocarcinoma is low, with no evaluation of efficacy and safety of ICI combined with chemotherapy. The DURIGAST PRODIGE 59 study is a randomised, multicentre, phase II study designed to assess the efficacy and safety of the combination of FOLFIRI + Durvalumab +/- Tremelimumab as 2nd line treatment of patients with advanced gastric/GEJ adenocarcinoma. Here, we report data from the safety run-in phase with FOLFIRI Durvalumab (arm A) or FOLFIRI Durvalumab and Tremelimumab (arm B). Among the 11 patients included, 63.6% experienced at least one grade 3-4 adverse events (AEs) related to the treatment, most frequently neutropenia (36.4%). There was only one immune-related AE (grade 2 hyperthyroidism). Ten serious AEs were described among six patients, but only two were related to the treatment, due to the chemotherapy. One seizure epilepsy related to a brain metastasis was observed, but was not related by the investigator to the treatment. However, the Independent Data Monitoring Committee recommended brain imaging at inclusion. This safety run-in phase demonstrates an expected safety profile of FOLFIRI with Durvalumab +/- Tremelimumab combination allowing the randomised phase II.
Phase II trial of irinotecan plus oxaliplatin and 5-fluorouracil/leucovorin in patients with untreated metastatic gastric adenocarcinoma. [2022]This nonrandomized open label phase II study evaluated the efficacy and safety of FOLFOXIRI in metastatic or recurrent gastric cancer patients.
A Multicenter Clinical Phase II Study of FOLFOXIRI Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer: QUATTRO Study. [2022]FOLFOXIRI (Fluorouracil, folinate, oxaliplatin, and irinotecan) plus bevacizumab improved progression-free survival (PFS) and overall survival in patients with metastatic colorectal cancer (mCRC), compared with FOLFIRI (fluorouracil, folinate, and irinotecan) plus bevacizumab, but significantly increased the incidences of adverse events. The efficacy and safety profiles of FOLFOXIRI plus bevacizumab in ethnic Asian patients have not been established yet.
FOLFIRI chemotherapy in patients with advanced non resectable esophageal or junctional adenocarcinoma: a pilot study. [2013]In this prospective pilot study, we assessed the efficacy and safety of the FOLFIRI regimen (irinotecan 180 mg/mยฒ, leucovorin 200 mg/mยฒ d1 followed by bolus 400 mg/mยฒ 5-fluorouracil (5-FU) and by a 46-h 2400 mg/mยฒ 5-FU infusion, every 2 weeks) in patients with advanced esophageal or junctional adenocarcinoma. Twenty-nine patients were included. A complete response was obtained in 2 patients, a partial response in 7 patients (objective response rate 31.0%). Stable disease was obtained in 13 patients (disease control rate 75.9%). The median progression-free and overall survivals were 5.9 and 8.6 months, respectively. One patient died from chemotherapy-related diarrhea after one cycle but this patient presented concomitant disease progression with cerebral metastases. We observed one additional grade 4 diarrhea, one grade 3 vomiting, and two grade 3 neutropenias. To conclude, FOLFIRI regimen appears quite active, with an acceptable safety profile in patients with advanced esophageal or junctional adenocarcinoma.
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]Label="LESSONS LEARNED">The safety profile in the patient groups who received FOLFIRI and simtuzumab did not differ from that in the FOLFIRI and placebo group.The addition of simtuzumab to chemotherapy with FOLFIRI does not improve clinical outcomes in patients with metastatic KRAS mutant colorectal carcinoma.
[A case of esophageal cancer associated with colon cancer successfully treated with combination chemotherapy of FOLFOX and concurrent radiotherapy]. [2013]The standard chemotherapy regimen for esophageal cancer is cisplatin and 5-fluorouracil (5-FU). We herein report a case of esophageal cancer associated with colon cancer, which was treated with combination chemotherapy of FOLFOX. The patient received chemotherapy of modified FOLFOX6 (mFOLFOX6) at dosages of 80% of standard regimen (oxaliplatin 68 mg/m2, levofolinate calcium 160 mg/m2, bolus 5-FU 320 mg/m2, and followed by continuous 5-FU 1,920 mg/m2/ 46 hr) in combination with radiotherapy (total 61.6 Gy). He developed grade 3 leukopenia after 2 courses of mFOLFOX6 and the 3rd course was started at dosages of 70% of standard regimen with 1 week delay. After that, no other adverse event without grade 2 esophagitis was appeared. Esophagogram revealed a partial response in primary tumor of the esophagus after 3 courses of chemotherapy with radiotherapy and blood chemistry examination showed negative squamous cell carcinoma antigen. One month after chemoradiotherapy, esophagogram revealed tracheoesophageal fistula, but tumor of the esophagus was well controlled. FOLFOX regimen combined with radiotherapy is well tolerated and effective for inoperable esophageal cancer. FOLFOX cannot be used for esophageal cancer in Japan, so clinical trial of FOLFOX for esophageal cancer should be conducted in the near future in Japan.
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]This study documents the clinical efficacy and toxicity of S-1 and paclitaxel (S1/PTX) in patients with unresectable or postoperative recurrent esophageal squamous cell carcinoma (ESCC) who had been previously treated with fluorouracil (5FU), cisplatin, and docetaxel.
Long-Term Survival in Gastroesophageal Junction Adenocarcinoma: Ramucirumab. [2020]We report a case of long-term survival with complete response of liver metastases within RAINBOW, a randomized, controlled trial of ramucirumab 8 mg/kg intravenously (days 1, 15) versus placebo, both plus paclitaxel 80 mg/m2 intravenously (days 1, 8, 15), every 4 weeks in patients with previously treated advanced gastroesophageal junction adenocarcinoma. A 64-year-old man with gastroesophageal junction adenocarcinoma and liver metastases received first-line folinic acid, 5-fluorouracil plus oxaliplatin (FOLFOX) following jejunostomy. On liver progression, he enrolled in RAINBOW (April 2012), receiving ramucirumab. In November 2013, positron emission tomography scan was consistent with complete metabolic response, confirmed by a follow-up scan in March 2016.