Chemotherapy for Stomach Cancer

(TOGAR Trial)

No longer recruiting at 4 trial locations

Overseen By Tannaz Armaghany

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Baylor College of Medicine

Disqualifiers: Metastatic disease, Prior chemotherapy, 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)

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

Compensation: Varies

Number of Visits: 17

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two different chemotherapy routines to determine which is more effective for people with stomach cancer. One group receives all their chemotherapy before surgery, while the other group receives some before and some after surgery. The goal is to discover which approach helps more people complete their treatment. The trial seeks participants with stomach cancer classified as Siewert type II or III who are eligible for surgery and chemotherapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that the combination of three drugs—docetaxel, fluorouracil, and oxaliplatin—known as the FLOT regimen, treats stomach cancer. Studies have found that this treatment often causes many tumors to shrink or disappear. However, it can also lead to more side effects.

In earlier studies, patients experienced common side effects while on this treatment. These side effects, typical with chemotherapy, include nausea, tiredness, and a reduced ability to fight infections. The overall safety of this combination aligns with expectations for these chemotherapy drugs.

The FLOT regimen is widely used and available for treating stomach cancer, so doctors understand its safety and effects well. While this treatment is being tested in this study, information from past studies can help reassure participants about its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the FLOT-TNT and FLOT-POP regimens for stomach cancer because they utilize a unique combination of chemotherapy drugs—Docetaxel, Fluorouracil, and Oxaliplatin—in a strategic sequence. Unlike typical treatments that may deliver chemotherapy post-surgery, the FLOT-TNT regimen administers all chemotherapy cycles before surgery, potentially shrinking tumors more effectively and enhancing surgical outcomes. On the other hand, the FLOT-POP regimen includes both pre- and post-operative chemotherapy, which might offer a balanced approach to managing cancer cells around the time of surgery. This innovative timing and combination of drugs could improve patient outcomes and provide a new standard for treating stomach cancer.

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

This trial will compare two treatment approaches for stomach cancer using the FLOT regimen, which includes docetaxel, fluorouracil, and oxaliplatin. Studies have shown that FLOT is highly effective for advanced stomach cancer. Participants in Arm A will receive all four cycles of FLOT as total neoadjuvant chemotherapy before surgery. Participants in Arm B will receive two cycles of pre-operative FLOT and two cycles of post-operative FLOT. Adding docetaxel has improved survival rates compared to other chemotherapy options. Research suggests that this three-drug combination is often chosen for potentially curable stomach cancer. In one study, about 47% of patients responded well to a similar treatment, indicating its potential effectiveness. While side effects can occur, FLOT remains a promising option for those battling stomach cancer. ^{1 3 4 6 7}

Who Is on the Research Team?

Tannaz Armaghany

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

Adults with confirmed gastric or gastroesophageal junction adenocarcinoma, who are fit for chemotherapy and surgery aimed at curing the cancer. They must have good organ function, no distant metastases, and be able to follow trial procedures. Women of childbearing age need a negative pregnancy test and agree to use contraception.

Inclusion Criteria

Must provide written informed consent

Must have life expectancy of greater than 3 months

My cancer has not spread to distant parts of my body, confirmed by recent tests.

Exclusion Criteria

Positive cytology for metastatic disease on diagnostic laparoscopy peritoneal fluid

My cancer has spread beyond the regional lymph nodes.

My cancer has spread to other parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy (Arm A)

Participants receive 4 cycles of FLOT chemotherapy before surgery

16 weeks

8 visits (in-person)

Surgery (Arm A)

Surgery is performed 4 weeks after the last chemotherapy cycle

1 week

1 visit (in-person)

Perioperative Chemotherapy (Arm B)

Participants receive 2 cycles of FLOT chemotherapy before and 2 cycles after surgery

24 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Fluorouracil
• Oxaliplatin

Trial Overview The study is testing two approaches using FLOT chemotherapy: one where all treatment is given before surgery (Total Neoadjuvant - FLOT-TNT) versus the standard method where it's given before and after surgery (Perioperative - FLOT-POP). The goal is to see which approach has better completion rates.

How Is the Trial Designed?

Group I: Arm B: FLOT-POP ( Standard Arm) Experimental Treatment 5 Interventions

Arm B us the standard perioperative arm with 2 cycles of pre-operative FLOT ( 4 treatment sessions) and 2 cycles ( 4 treatment sessions) of post-operative FLOT. Post-surgery FLOT will start 4-6 weeks post surgery. Each cycle of chemotherapy consists of 28 days and consists of 2 chemotherapy sessions given every 14 days. The total number of chemotherapy sessions in arm B is 8. Every effort should be done to have surgery done in week 12 ( -1 to +2 weeks) post completion of cycle 2 on ARM B.

Group II: Arm A: FLOT-TNT ( Investigational Arm) Experimental Treatment 5 Interventions

Arm A is the investigational arm with all 4 cycles of FLOT given as total neoadjuvant chemotherapy prior to surgery. Each cycle is 28 days and consists of 2 chemotherapy sessions given every 14 days. The total number of chemotherapy sessions in Arm A is 8. Every effort will be made to have surgery in week 20 ( -1 to +2 weeks), 4 weeks post C4 on arm A.

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?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Published Research Related to This Trial

In a phase II study involving 58 patients with advanced gastric cancer, the combination of docetaxel, fluorouracil, and leucovorin (TFL) showed a moderate overall response rate of 26%, with 4 complete and 11 partial responses observed.

The TFL regimen was found to have manageable toxicity, with neutropenia being the most common severe side effect (30% of patients), and no toxic deaths reported, indicating a favorable safety profile for this chemotherapy combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination docetaxel (Taxotere), fluorouracil, and leucovorin (TFL), as first-line chemotherapy in advanced gastric cancer: a Hellenic Cooperative Oncology Group phase II study. Papakostas, P., Tsavdaridis, D., Kosmidis, P., et al.[2022]

In a small study of five patients with recurrent or unresectable gastric cancer, a combination of docetaxel and doxifluridine showed a 40% overall response rate, indicating potential efficacy for this treatment.

A specific case of a 71-year-old man with multiple skin metastases from gastric cancer demonstrated complete tumor disappearance after 3 weeks of this chemotherapy, with no recurrence observed for over a year, suggesting a promising treatment outcome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A case of multiple skin metastases from gastric cancer successfully treated with docetaxel combined with doxifluridine]. Mori, T., Ikeda, Y., Okamoto, K., et al.[2018]

The combination of docetaxel and the oral drug S-1 showed a high overall response rate of 56.3% in 48 patients with advanced or recurrent gastric cancer, with a tumor control rate of 93.8%.

The treatment was generally well tolerated, with manageable side effects; the most common severe toxicities were hematologic, such as neutropenia, but no grade 4 nonhematologic toxicities were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of docetaxel and S-1 combination therapy for advanced or recurrent gastric cancer. Yoshida, K., Ninomiya, M., Takakura, N., et al.[2022]

In a study of 33 patients with relapsed gastric cancer, docetaxel as a third-line therapy showed a partial response in 15% of patients and stable disease in 27%, with a median overall survival of 4.7 months.

While docetaxel is a feasible treatment option, it is associated with significant hematologic toxicities, including grade 3 to 4 neutropenia in 58% of patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Third-line docetaxel chemotherapy for recurrent and metastatic gastric cancer. Lee, JH., Kim, SH., Oh, SY., et al.[2022]

In a feasibility study involving 21 patients with advanced gastric cancer, a triplet chemotherapy regimen of paclitaxel, cisplatin, and S-1 showed a promising overall response rate of 67%, indicating significant antitumor activity.

The treatment was well-tolerated, with most toxicities being manageable; serious side effects like grade 3 leucopenia and neutropenia occurred in only a minority of patients, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility study of triplet combination chemotherapy of paclitaxel, cisplatin and S-1 for advanced gastric cancer. Fujitani, K., Hasegawa, H., Hirao, M., et al.[2015]

A phase II study found that combining docetaxel (85-100 mg/m2) with cisplatin (75 mg/m2) resulted in a 56% overall response rate in patients with advanced gastric cancer, indicating promising efficacy.

The combination therapy has a manageable safety profile, and adding up to 300 mg/m2 of 5-fluorouracil (5-FU) via continuous infusion does not significantly increase toxicity, suggesting potential for further treatment optimization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European experience of docetaxel and cisplatin in advanced gastric cancer. Roth, AD.[2019]

In a study involving 40 patients with advanced or recurrent gastric cancer, the combination of doxifluridine and docetaxel showed a modest overall response rate of 17.5%, indicating some efficacy as a second-line treatment.

The treatment was generally well tolerated, with significant hematological toxicities like neutropenia occurring in 52.5% of patients, but serious non-hematological side effects were rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of doxifluridine and docetaxel combination chemotherapy for advanced or recurrent gastric cancer. Yoshikawa, T., Tsuburaya, A., Shimada, K., et al.[2021]

The combination of docetaxel, cisplatin, and 5-fluorouracil showed an overall effective rate of 48.4% in treating advanced gastric cancer, with a higher success rate of 64.7% in patients who had not received prior treatments.

The treatment regimen was well-tolerated, with most side effects being mild (grade 1 or 2), including myelosuppression and gastrointestinal reactions, indicating a favorable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Weekly dosage of docetaxel combined with cisplatin and 5-fluorouracil in the treatment of advanced gastric cancer]. Zhang, AM., Ye, S.[2018]

The biweekly FLOT chemotherapy regimen, which includes oxaliplatin, leucovorin, fluorouracil, and docetaxel, showed a 57.7% objective response rate in 54 patients with metastatic gastric cancer, indicating its efficacy.

Despite some significant side effects like neutropenia and leukopenia, the treatment demonstrated a favorable safety profile, with only 3.8% of patients experiencing complicated neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Al-Batran, SE., Hartmann, JT., Hofheinz, R., et al.[2022]

Docetaxel has been shown to be highly effective in treating advanced gastric cancer, especially when combined with other drugs like cisplatin and 5-fluorouracil, leading to improved tumor progression and survival rates in clinical trials.

The TAX325 Phase III study confirmed that the docetaxel, cisplatin, and 5-FU combination (DCF) outperformed the cisplatin and 5-FU regimen, resulting in docetaxel's approval for use in advanced gastric cancer by major regulatory agencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in the treatment of gastric cancer. Thuss-Patience, PC., Kretzschmar, A., Reichardt, P.[2018]

Docetaxel has shown promising efficacy in treating advanced gastric cancer, with overall response rates (ORRs) ranging from 17.5% to 52% when combined with other agents like cisplatin and 5-FU, indicating it could be a strong option alongside traditional regimens like ECF and PELF.

The safety profile of docetaxel-based treatments is acceptable, with manageable side effects such as neutropenia, suggesting that it can be integrated into treatment plans for advanced gastric cancer without significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in advanced gastric cancer. Haller, DG., Misset, JL.[2019]

In a study of 23 patients with unresectable advanced gastric cancer, the combination of docetaxel and doxifluridine showed a 17.4% overall response rate, indicating some effectiveness as a second-line or third-line chemotherapy option.

The treatment resulted in a median overall survival of 4.6 months and a one-year survival rate of 26.1%, with manageable side effects such as neutropenia and fatigue, suggesting a promising therapeutic index for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bi-weekly docetaxel and doxifluridine combination therapy in pretreated patients with unresectable and/or advanced gastric cancer]. Nukaya, H., Kajino, S., Tokuda, H., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6693711/

Docetaxel, Oxaliplatin, and 5‐Fluorouracil (DOF) in ... The combination of docetaxel, cisplatin, and 5‐fluorouracil (5‐FU) demonstrates high response rates in advanced gastric cancer, albeit with increased toxicity.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00526110?cond=%22Gastrointestinal%20System%20Disease%22&intr=%22Antimetabolites%22&viewType=Table&rank=6

Study Details | Docetaxel, 5-Fluorouracil and Oxaliplatin in ... Phase I Objectives. Primary: 1. The primary objective of this study is to determine the maximum tolerated dose (MTD) of Docetaxel combined with ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419313365

Docetaxel plus oxaliplatin with or without fluorouracil or ... The rate of tumour response (complete or partial) was 46.6% (95% CI 35.9–57.5) for TEF versus 23.1% (14.3–34.0) for TE and 25.6% (16.6–36.4) for TEX. The ...

4. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00154-8/fulltext?rss=yes

Docetaxel as part of first-line chemotherapy for gastric cancer For perioperative therapy in potentially curable patients, FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) is the preferred ...

5. journals.lww.com journals.lww.com/ojji/fulltext/2020/04030/survival_outcomes_with_docetaxel,_oxaliplatin,_and.6.aspx

Survival Outcomes with Docetaxel, Oxaliplatin, and... The three-drug regimen of docetaxel, oxaliplatin, and fluorouracil (DOF) has been shown to improve survival compared to the two-drug regimen of docetaxel and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31138725/

Docetaxel, Oxaliplatin, and 5-Fluorouracil (DOF) in ... - PubMed Median overall survival was 10.3 months. Conclusion: DOF demonstrates a high response rate, expected safety profile, and prolonged survival and remains an ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04840264

Docetaxel, Oxaliplatin and 5-FU for Gastric Cancer With ... This is a multi-center, non-randomized, 3-cohort, phase II trial, evaluating a triplet combination of docetaxel, oxaliplatin and fluorouracil for gastric cancer