Chemotherapy Decision Test for Gastroesophageal Cancer

Overseen By University of California Irvine Medical

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, Irvine

Must not be taking: Investigational agents

Disqualifiers: Metastases, Uncontrolled illness, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for selecting chemotherapy treatments for individuals with certain types of gastroesophageal cancer, affecting the stomach or the junction where the stomach meets the esophagus. The trial aims to determine if a personalized approach, based on specific tests, can assist doctors in choosing the optimal chemotherapy plan. Participants will begin with standard treatments, such as Docetaxel (a chemotherapy drug), and may switch based on their response. This trial targets individuals with Stage IB, II, or III adenocarcinoma of the stomach or gastroesophageal junction who can undergo chemotherapy for up to six months. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new personalized approach.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on any other investigational agents while participating in this trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that FLOT and FOLFOX chemotherapy treatments are generally well-tolerated by patients. Studies indicate that these treatments do not significantly increase the risk of severe side effects. They help shrink tumors before surgery in patients with stomach or gastroesophageal junction cancer. While side effects can occur, they are usually manageable and don't lead to major problems. This makes FLOT and FOLFOX good options for those considering chemotherapy as part of their cancer treatment plan. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it's using ctDNA testing to guide chemotherapy decisions for gastroesophageal cancer. Unlike traditional treatments where decisions are often based on fixed protocols, this approach personalizes therapy by monitoring tumor response through blood tests that check for specific markers like CEA and CA19-9. This could lead to more tailored and effective treatment plans, potentially improving outcomes and reducing unnecessary side effects by adjusting therapies based on real-time feedback from the cancer itself.

What evidence suggests that this trial's treatments could be effective for gastroesophageal cancer?

Research has shown that both FLOT and FOLFOX chemotherapy treatments hold promise for stomach and gastroesophageal junction cancers. In one study, 77% of patients treated with FLOT experienced significant tumor reduction or complete disappearance. Another study found that 76.8% of patients treated with FLOT remained cancer-free after one year. FOLFOX has demonstrated similar success in prolonging survival without cancer recurrence. In this trial, participants will receive neoadjuvant chemotherapy with either FLOT or FOLFOX. These treatments primarily aim to reduce tumor size before surgery. Additionally, ctDNA testing in this trial can help customize treatment plans based on individual responses, potentially leading to better outcomes. ^{6 7 8 9 10}

Who Is on the Research Team?

Farshid Dayyani

Principal Investigator

Chao Family Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with Stage IB, II or III gastroesophageal adenocarcinoma who can consent to treatment. They must have a positive ctDNA blood test and be fit enough for chemotherapy (ECOG ≤2). Pregnant women, those with other active cancers, uncontrolled illnesses, or known metastases from GEA are excluded.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

My cancer is confirmed to be in the stomach or where my stomach meets my esophagus.

My stomach or esophagus cancer is at an early but operable stage.

Exclusion Criteria

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

My cancer has spread from my stomach or esophagus.

Patients may not be receiving any other investigational agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive neoadjuvant chemotherapy guided by ctDNA assay results. If no decline in ctDNA is detected after 4 cycles, treatment is switched to a different chemotherapy regimen.

12-16 weeks

Regular visits for chemotherapy cycles

Surgery

Participants undergo gastrectomy if ctDNA levels are favorable after chemotherapy.

1-2 weeks

Adjuvant Treatment

Adjuvant treatment is administered based on the investigator's discretion following surgery.

Variable

Follow-up

Participants are monitored for safety, effectiveness, and relapse-free survival after treatment.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• ctDNA Blood Test
• Docetaxel
• FLOT
• FOLFIRI
• FOLFIRINOX
• FOLFOX
• Irinotecan
• Nivolumab
• Paclitaxel
• Pembrolizumab

Trial Overview The RANT-GC Trial tests if using ctDNA results to guide neoadjuvant chemotherapy improves outcomes in stomach or gastroesophageal junction cancer. It includes various chemo regimens like FOLFIRINOX and NIVOLUMAB, alone or combined.

How Is the Trial Designed?

Group I: Neoadjuvant chemotherapy with ctDNA testing Experimental Treatment 10 Interventions

The patients will be treated with one of the standard neoadjuvant protocols (FLOT or FOLFOX.) If patient response to their treatment, as measured by CT Scans or MRI results or blood tests done to look tumor markers such as carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA19-9) a change in adjuvant treatment will be made.

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

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

BillionToOne, Inc

Collaborator

Natera, Inc.

Industry Sponsor

Trials

56

Recruited

50,700+

Published Research Related to This Trial

The combination of nivolumab (an anti-PD-1 antibody) with irinotecan and a fluoropyrimidine showed a disease control rate of 73.3% in 15 patients with advanced unresectable gastroesophageal cancers, indicating potential efficacy in this challenging patient population.

The treatment was generally feasible, with a median progression-free survival of 7 months and overall survival of 13.3 months, although 33% of patients experienced dose delays or adjustments primarily due to fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in Combination with Irinotecan and 5-Fluorouracil (FOLFIRI) for Refractory Advanced Gastroesophageal Cancer. Rogers, JE., Xiao, L., Trail, A., et al.[2023]

In a phase II trial involving 78 patients with esophageal squamous cell carcinoma who did not respond to first-line chemotherapy, paclitaxel (PTX) significantly improved overall survival (8.8 months) compared to docetaxel (DTX) (7.3 months).

PTX also demonstrated better progression-free survival (4.4 months vs. 2.1 months) and a higher response rate (25.6% vs. 7.7%), while having a more manageable safety profile with fewer severe side effects compared to DTX.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of docetaxel versus paclitaxel in patients with esophageal squamous cell carcinoma refractory to fluoropyrimidine- and platinum-based chemotherapy: OGSG1201. Yamamoto, S., Kawakami, H., Kii, T., et al.[2021]

In a study of 124 patients with advanced or recurrent esophageal cancer who had previously received platinum-based chemotherapy, paclitaxel (PTX) showed higher objective response rates (25.7% vs. 10.3%) and disease control rates (60.0% vs. 34.6%) compared to docetaxel (DTX).

While both treatments had similar overall survival rates (6.1 months for DTX vs. 7.2 months for PTX), PTX was associated with fewer severe side effects, such as grade 3-4 neutropenia (21.1% for PTX vs. 48.8% for DTX) and febrile neutropenia (5.3% for PTX vs. 20.9% for DTX), making it a more feasible option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective comparison of docetaxel and paclitaxel for patients with advanced or recurrent esophageal cancer who previously received platinum-based chemotherapy. Mizota, A., Shitara, K., Kondo, C., et al.[2018]

Paclitaxel demonstrated significant effectiveness against esophageal cancer in a phase II trial, indicating its potential as a treatment option for this type of cancer.

Irinotecan has proven to be effective as a single-agent treatment for both gastric and colorectal cancers, while docetaxel showed notable activity in advanced gastric cancer and a 29% response rate in pancreatic cancer, highlighting its versatility in treating various cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New systemic drugs in the treatment of gastrointestinal cancer. Ogawa, M.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12270292/

Comparative efficacy of adjuvant FOLFOX vs. FLOT ... This study aimed to compare the efficacy of adjuvant FLOT and FOLFOX regimens in enhancing survival outcomes in patients with locally advanced gastric cancer ...

2. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.16_suppl.e16120

Comparative efficacy of adjuvant FOLFOX versus FLOT ... At 16 months, DFS and OS rates were 66% and 82%, respectively. No significant differences were observed in DFS (HR: 0.63, 95% CI: 0.30-1.33, p = ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11254397/

Outcomes of locally advanced gastric and ... In our study, the overall pathological response rate after neoadjuvant FLOT in Gastric cancer (GC) and GEJ cancer was 77%. The CR was achieved in 11.4% of ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e16129

Analysis of effectiveness of FLOT perioperative ... Overall, 1- and 3-year survival were 78,6% and 34,9% respectively, disease free survival was 76,8% and 39% respectively. Conclusions: The FLOT ...

5. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/esophageal-cancer-flot-perioperative-chemotherapy

FLOT Improves Survival in Locally Advanced Esophageal ... A large clinical trial looks to have settled a debate over how best to treat most people with locally advanced esophageal cancer.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9872182/

Efficacy and safety of FLOT regimen vs DCF, FOLFOX ... For resectable gastric cancer patients, the perioperative FLOT regimen led to a significant improvement in patients' OS and PFS versus ECF, DCF, and FOLFOX ...

7. esmogastro.org esmogastro.org/article/S2949-8198(24)00011-6/fulltext

Safety and efficacy of perioperative FLOT regimen in ... In this study, we retrospectively investigated the safety and efficacy of the perioperative FLOT regimen in Japanese patients with localized ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.359

An interim safety analysis from the phase III PREVENT trial ... The safety data showed no abnormalities or evidence increase in toxicity-rates including postoperative complications or increased severity of documented events.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04447352

NCT04447352 | HIPEC + FLOT vs. FLOT Alone in Patients ... This is a multicenter, randomized, controlled, open-label study evaluating efficacy and safety of perioperative FLOT chemotherapy plus intraoperative HIPEC ...

10. targetedonc.com targetedonc.com/view/durvalumab-plus-flot-improves-os-in-g-gej-adenocarcinoma

Durvalumab Plus FLOT Improves OS in G/GEJ ... Durvalumab combined with FLOT chemotherapy significantly improved overall survival in resectable gastric/gastroesophageal junction ...