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

Trial Summary

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.

What data supports the effectiveness of the drugs used in the Chemotherapy Decision Test for Gastroesophageal Cancer?

Research shows that paclitaxel has significant activity against esophageal cancer, and irinotecan is effective for gastric and colorectal cancers. Docetaxel has shown significant activity in advanced gastric cancer and a 29% response rate in pancreatic cancer. Additionally, combining irinotecan with nivolumab may offer some advantage for advanced gastroesophageal cancer. ^{1 2 3 4 5}

Is the chemotherapy combination of docetaxel and irinotecan safe for humans?

Research has shown that the combination of docetaxel and irinotecan is generally safe for treating advanced esophageal cancer, with specific doses tested to ensure safety. ^{4 6 7 8 9}

What makes the chemotherapy decision test for gastroesophageal cancer unique?

This treatment is unique because it combines multiple drugs like Docetaxel, Paclitaxel, and Irinotecan, which have shown significant activity in treating various gastrointestinal cancers, including esophageal and gastric cancers. The combination aims to enhance efficacy by using drugs with different mechanisms of action, potentially offering a more comprehensive approach for patients who have not responded to standard treatments. ^{2 3 4 5 10}

What is the purpose of this trial?

This is a phase 1b prospective, single arm, open-label trial determining the efficacy and feasibility of using a ctDNA assay (test) result to help guide neoadjuvant chemotherapy in subjects with Stage IB, II or Stage III adenocarcinoma of the stomach or gastroesophageal junction (GEA).

Research Team

Farshid Dayyani

Principal Investigator

Chao Family Comprehensive Cancer Center

Eligibility Criteria

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.

Patients may not be receiving any other investigational agents

History of allergic reactions attributed to agents used in study

Timeline

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

Treatment Details

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.

Participant Groups

Group I: Neoadjuvant chemotherapy with ctDNA testing Experimental Treatment 9 Interventions

The patients will be treated with one of the standard neoadjuvant protocols (FLOT or FOLFOX.) If no decline in ctDNA detected after 4 cycles, treatment will be switched to a different chemotherapy backbone (e.g. irinotecan based regimen, or taxane based if not used upfront). ctDNA will be re-evaluated after 3 cycles (if a 21 day regimen) or 4 cycles (if a 14 day regimen) of the 2nd line regimen. If ctDNA is lower than the previous measurement, then the same regimen continues for 3-4 more cycles (depending on 14 day or 21 day cycle), followed by gastrectomy. Adjuvant treatment is given based on the investigator's discretion.

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+

Natera, Inc.

Industry Sponsor

Trials

56

Recruited

50,700+

Findings from Research

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Nivolumab in Combination with Irinotecan and 5-Fluorouracil (FOLFIRI) for Refractory Advanced Gastroesophageal Cancer. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Weekly docetaxel, cisplatin, and irinotecan (TPC): results of a multicenter phase II trial in patients with metastatic esophagogastric cancer. [2021]

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

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

4. Switzerland 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. [2018]

5. England 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. [2021]

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

Phase I study of docetaxel, capecitabine, and carboplatin in metastatic esophagogastric cancer. [2019]

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

Phase II studies on docetaxel alone every third week, or weekly in combination with gemcitabine in patients with primary locally advanced, metastatic, or recurrent esophageal cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Phase II trial of docetaxel-irinotecan combination in advanced esophageal cancer. [2021]

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

Docetaxel combined with irinotecan or 5-fluorouracil in patients with advanced oesophago-gastric cancer: a randomised phase II study. [2021]

10. Japan pubmed.ncbi.nlm.nih.gov

Concordance of clinical diagnosis of T classification among physicians for locally advanced unresectable thoracic esophageal cancer. [2018]