Chemotherapy for Stomach Cancer with Peritoneal Carcinomatosis

(STOPGAP Trial)

Overseen By University of California, Irvine Medical Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Irvine

Disqualifiers: Metastases, Obstruction, Infection, Cancer, 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

Compensation: Varies

Number of Visits: 7

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating stomach cancer that has spread to the abdominal lining, known as peritoneal carcinomatosis. The study evaluates the safety and effectiveness of using a combination of chemotherapy drugs—Fluorouracil, Leucovorin, and Paclitaxel—both in the bloodstream and directly in the abdomen. Individuals with stomach or gastroesophageal cancer, who have undergone at least three months of treatment without the cancer spreading to organs like the liver or lungs, and whose cancer has spread to the abdominal lining, might be suitable candidates for this trial. Participants will receive this chemotherapy combination on specific days within a 21-day cycle for three months. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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 to get a clear answer.

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

Previous studies have shown that using paclitaxel directly in the abdomen (intraperitoneal or IP) is safe for patients. A common side effect was a drop in white blood cells, known as neutropenia, when treatments were given weekly. However, the overall safety was deemed acceptable. Research also shows that IP paclitaxel treatments are safe and promising for patients with stomach cancer that has spread to the abdominal lining.

For paclitaxel given through a vein (intravenous or IV), studies indicate it is generally well-tolerated and helps patients live longer when combined with other treatments. In one study, patients who received both IP and IV paclitaxel lived for more than 19 months on average, which is encouraging.

Fluorouracil, an older chemotherapy drug, is also part of the treatment and has been used safely for various cancers. Some studies suggest that combining it with other drugs can help stomach cancer patients live longer.

Leucovorin is often used with fluorouracil to enhance its effectiveness. It has a low rate of complications and is generally safe, contributing to an average survival of about 19 months in some studies.

Overall, previous research has shown that the combination of these treatments is safe, with manageable side effects and potential benefits for patients with advanced stomach cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment because it combines both intraperitoneal and intravenous delivery of paclitaxel, which is a unique approach for treating stomach cancer with peritoneal carcinomatosis. Unlike standard treatments that typically involve systemic chemotherapy alone, this method targets cancer cells directly in the abdominal cavity, potentially enhancing efficacy and reducing systemic side effects. Additionally, the integration of fluorouracil and leucovorin with paclitaxel might improve the overall response by attacking cancer cells through multiple mechanisms, offering hope for better outcomes in this challenging condition.

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

In this trial, participants will receive a combination of treatments, including paclitaxel administered directly in the abdomen along with regular IV treatment. Studies have shown that this approach can extend the lives of people with stomach cancer that has spread to the abdomen, with an average survival of 19.4 months. Fluorouracil (5-FU) is another component of the regimen, known for its effectiveness in treating stomach cancer, especially when combined with other treatments. Leucovorin often accompanies 5-FU to enhance its efficacy. Overall, this combination of treatments shows promising results in helping people with advanced stomach cancer live longer. ^{2 6 7 8 9}

Who Is on the Research Team?

Maheswari Senthil, MD

Principal Investigator

Chao Family Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Adults aged 18-75 with gastric or gastroesophageal junction cancer and peritoneal carcinomatosis, who've had at least three months of initial treatment without visceral metastasis. Participants need good organ function, no severe heart conditions, infections, or other cancers in the last 3 years. Pregnant women are excluded and contraception is required during the trial.

Inclusion Criteria

Leukocytes: ≥ 2,000/mcL

I have stomach or gastroesophageal cancer and have been treated for at least 3 months without the cancer spreading to other organs.

You are expected to live for more than 6 months.

Exclusion Criteria

Inability to comply with study and follow-up procedures as judged by the Investigator

I am not pregnant or nursing and agree to use birth control during the study.

My cancer has spread to distant organs like the liver, lungs, or brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Systemic Therapy

Patients undergo systemic therapy for 3-4 months based on molecular markers

12-16 weeks

Regular visits as per oncologist's discretion

Intraperitoneal Chemotherapy

Patients receive IP Paclitaxel, IV Paclitaxel, 5-FU, and Leucovorin on Days 1 and 8 of every 21-day cycle for 3 months

12 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 weeks

1-2 visits (in-person)

Long-term Follow-up

Monitoring of progression-free survival and overall survival up to 12 months after last patient enrollment

Up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Fluorouracil
• Leucovorin
• Paclitaxel

Trial Overview The trial tests a combination of systemic chemotherapy (Leucovorin, Fluorouracil) followed by intraperitoneal Paclitaxel to see if it's safe and works for patients with stomach cancer that has spread to the lining of their abdomen.

How Is the Trial Designed?

Group I: SingleArm: Systemic therapy and IP Paclitaxel in Gastric/GEJ Cancer Peritoneal Carcinomatosis Experimental Treatment 3 Interventions

Patients will receive sequential intraperitoneal paclitaxel along with intravenous paclitaxel, 5-FU, and leucovorin on Days 1 and 8 of every 21 day cycle for 3 months.

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

Approved in United States as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Skin cancer

Approved in European Union as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Approved in Canada as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

Published Research Related to This Trial

In a study of 94 patients with severe peritoneal metastasis of gastric cancer, the sequential treatment of 5-fluorouracil (FL) followed by paclitaxel (PTX) resulted in significantly better overall survival (7.8 months) compared to best supportive care (2.0 months).

The combination treatment (FLTAX) showed similar overall survival to the sequential treatment but may be preferable due to challenges in identifying patients who can benefit from sequential therapy at the start of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical implications of using both fluoropyrimidine and paclitaxel in patients with severe peritoneal metastasis of gastric cancer: A post hoc study of JCOG1108/WJOG7312G. Arai, H., Inoue, E., Yamaguchi, K., et al.[2022]

The study found that fluorouracil, l-leucovorin, and paclitaxel at a lower dose (Level 1) is a feasible first-line treatment for patients with advanced gastric cancer and severe peritoneal metastasis, achieving a high completion rate of 92% for two treatment cycles.

Despite some serious side effects, including a treatment-related death, the recommended dose (Level 1) showed promising outcomes with a median overall survival of 8.0 months and a 44% response rate in reducing ascites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter feasibility study of combination therapy with fluorouracil, leucovorin and paclitaxel (FLTAX) for peritoneal disseminated gastric cancer with massive ascites or inadequate oral intake. Iwasa, S., Goto, M., Yasui, H., et al.[2022]

The combination of intraperitoneal docetaxel and S-1 chemotherapy, followed by surgery, was well tolerated in 18 advanced gastric cancer patients with peritoneal carcinomatosis, showing no treatment-related mortality.

After two cycles of neoadjuvant chemotherapy, 78% of patients had negative peritoneal cytology results, and 62.5% of those with measurable lymph node metastases showed a major response, indicating significant efficacy of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal docetaxel combined with S-1 for advanced gastric cancer with peritoneal dissemination. Fujiwara, Y., Takiguchi, S., Nakajima, K., et al.[2022]

The modified FOLFOX4 (m-FOLFOX4) chemotherapy regimen was found to be effective for treating colorectal cancer patients with peritoneal carcinomatosis, showing a median overall survival of 21.5 months in a study of 40 patients.

The study reported no treatment-related deaths, indicating a favorable safety profile, and identified factors like low carcinoembryonic antigen levels and good performance status as predictors of better survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Modified FOLFOX4 for Colorectal Cancer Patients with Peritoneal Carcinomatosis. Lee, DH., Oh, SY., Lee, YR., et al.[2021]

In a study of 49 gastric cancer patients with abdominal peritoneal carcinomatosis, those receiving combined intravenous and intraperitoneal chemotherapy showed significantly higher objective response and disease control rates compared to those receiving only intravenous chemotherapy.

The median survival time for patients in the combination therapy group was 15.03 months, which was significantly longer than the 6.57 months for the control group, with no significant difference in adverse effects between the two treatments, indicating that the combination therapy is both effective and tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy of Combination Intravenous and Intraperitoneal Chemotherapy in the Treatment of Gastric Cancer with Peritoneal Carcinomatosis. Zhang, S., Feng, R., Pan, Z., et al.[2019]

In a study of 64 patients with peritoneal carcinomatosis from colorectal cancer, those with smaller tumor sizes (< 5 cm) and complete cytoreduction (tumor nodules < 2.5 mm) had significantly better prognoses, indicating the importance of early and aggressive treatment.

The study suggests that cytoreductive surgery combined with postoperative intraperitoneal chemotherapy can lead to long-term disease-free survival in patients with small-volume peritoneal seeding, highlighting a potential effective intervention for this previously lethal condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peritoneal carcinomatosis from adenocarcinoma of the colon. Sugarbaker, PH., Schellinx, ME., Chang, D., et al.[2019]

In a phase I trial involving 4 gastric cancer patients, intraperitoneal (IP) paclitaxel at a dose of 60 mg/m2 showed a high concentration in the peritoneal cavity, with a peak plasma ratio of over 2000 at 3 hours post-administration, indicating effective delivery of the drug.

Despite challenges in drug delivery leading to only 3 evaluable patients, 2 out of these 3 showed a reduction in ascites, suggesting that IP paclitaxel could be a promising treatment option for managing peritoneal carcinomatosis in gastric cancer when used alongside other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal paclitaxel: a possible impact of regional delivery for prevention of peritoneal carcinomatosis in patients with gastric carcinoma. Kodera, Y., Ito, Y., Ito, S., et al.[2015]

In a study of 25 patients with advanced gastric cancer, the combination of paclitaxel and semimonthly 5-fluorouracil (5-FU) showed a high efficacy, with 60% of patients achieving partial remission and 8% achieving complete remission after two cycles of treatment.

The treatment was found to be safe, with no treatment-related deaths reported, and the main side effects included phlebitis, feeling disorder, and alopecia, indicating that the regimen has manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preliminary report of semimonthly 5-fluorouracil/leucovorin combined with paclitaxel in treatment of advanced gastric cancer (AGC)]. Zhou, NN., Zhou, ZM., Liu, MZ., et al.[2015]

In a study of 101 patients with severe peritoneal metastases of gastric cancer, the combination of 5-fluorouracil, l-leucovorin, and paclitaxel (FLTAX) showed a longer progression-free survival (5.4 months) compared to 5-FU/l-LV (1.9 months), indicating better disease control with FLTAX.

Although FLTAX did not significantly improve overall survival compared to 5-FU/l-LV (7.3 months vs. 6.1 months), it had a more favorable safety profile, with fewer severe adverse events, making it a potentially better option for patients who cannot tolerate traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II/III study of 5-fluorouracil/l-leucovorin versus 5-fluorouracil/l-leucovorin plus paclitaxel administered to patients with severe peritoneal metastases of gastric cancer (JCOG1108/WJOG7312G). Nakajima, TE., Yamaguchi, K., Boku, N., et al.[2021]

In a randomized phase II study of 100 patients with advanced gastric cancer, weekly administration of paclitaxel (wPTX) showed a longer median progression-free survival (3.7 months) compared to the best available 5-fluorouracil (5-FU) regimen (2.4 months), suggesting wPTX may be more effective in delaying disease progression.

The safety profile of wPTX was better than that of 5-FU, with lower incidences of severe side effects such as grade 4 neutropenia (2% for wPTX vs. 6% for 5-FU) and no treatment-related deaths, indicating that wPTX could be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of second-line chemotherapy with the best available 5-fluorouracil regimen versus weekly administration of paclitaxel in far advanced gastric cancer with severe peritoneal metastases refractory to 5-fluorouracil-containing regimens (JCOG0407). Nishina, T., Boku, N., Gotoh, M., et al.[2022]

Two women with peritoneal carcinomatosis of unknown origin showed positive responses to chemotherapy with paclitaxel plus carboplatin, suggesting this combination may be effective for this unique subgroup.

One patient had no residual tumor after surgery, while the other experienced complete resolution of ascites and lesions, indicating promising efficacy of the treatment that warrants further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin-induced complete remission in peritoneal carcinomatosis of unknown origin: a report of two cases and review of the literature. Wu, YY., Chang, JY., Chao, TY.[2022]

In a study involving 18 patients with advanced gastric cancer, the combination of paclitaxel and doxifluridine showed promising results, with 1 complete response and 5 partial responses observed.

The maximum tolerated dose (MTD) was not definitively established, but the recommended Phase II dose was determined to be 80 mg/m2 for paclitaxel combined with 533 mg/m2 of doxifluridine, indicating a potentially effective treatment regimen with manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A combination phase I study of weekly paclitaxel and doxifluridine in advanced gastric cancer patients. Takeyoshi, I., Makita, F., Tanahashi, Y., et al.[2015]

In a study of 35 patients with untreated advanced gastric cancer, the combination of bolus 5-fluorouracil, leucovorin, and weekly paclitaxel (FLTAX) resulted in a confirmed response rate of 43%, indicating promising efficacy for this treatment regimen.

The treatment demonstrated a manageable safety profile, with the most common severe side effects being neutropenia (54%) and sensory neuropathy (11%), suggesting that FLTAX could be a viable option for patients with advanced gastric cancer, especially those in poor general condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of bolus 5-fluorouracil and leucovorin combined with weekly paclitaxel as first-line therapy for advanced gastric cancer. Matsubara, J., Shimada, Y., Kato, K., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4644851/

Breakthrough therapy for peritoneal carcinomatosis of ... Clinical trials on methotrexate + 5-fluorouracil (5-FU), FOLFOX-4, and continuous 5-FU for PC of gastric cancer showed that the median survival time (MST) was ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0748798324015671

Review Article Outcomes of intraperitoneal chemotherapy ... Findings indicate a significant survival benefit in patients receiving CIPC (HR 0.66 [95%CI, 0.49–0.88], P = 0.0054)(Lu et al., unpublished data). This trial ...

3. ascopubs.org ascopubs.org/doi/10.1200/jco.2010.28.15_suppl.4052

Randomized phase II study of best-available 5-fluorouracil ... Randomized phase II study of best-available 5-fluorouracil (5-FU) versus weekly paclitaxel in gastric cancer (GC) with peritoneal metastasis ...

4. ar.iiarjournals.org ar.iiarjournals.org/content/37/12/7037

FOLFOX as First-line Therapy for Gastric Cancer with ... Results: Only 39 (10%) of 378 AGC patients had severe PM; 10 received FOLFOX. The median progression-free and overall survivals were 7.5 and 13.2 months, ...

5. tandfonline.com tandfonline.com/doi/abs/10.1179/joc.2007.19.4.359

The Effectiveness of Intravenous 5-Fluorouracil-Containing ... Intravenous 5-FU-containing chemotherapy after curative resection had a slightly significant improvement in 3-, 5- and 7-year overall survival ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10046173/

Gastric Cancer with Peritoneal Metastases: Current Status ... The best survival results were observed in the HIPEC group, with a median OS of 18.8 months vs. 12.1 months, and without differences in terms of ...

7. cancerdiagnosisprognosis.org cancerdiagnosisprognosis.org/article/190/indications-safety-efficacy-and-survival-benefit-of-intraperitoneal-chemotherapy-in-patients-with-advanced-gastric-cancer

Indications, Safety, Efficacy and Survival Benefit of ... In this study, we aimed to evaluate the efficacy, safety, and survival benefit of intraperitoneal chemotherapy as an alternate or complementary ...

8. academic.oup.com academic.oup.com/oncolo/article/30/9/oyaf219/8222739

Gastrointestinal CancerEmerging treatment modalities for ... Median overall survival (OS) ranged from 6.5 to 7.4 months with systemic chemotherapy, 13.0 to 23.9 months with IP chemotherapy, 6.8 to 13.0 ...

9. ar.iiarjournals.org ar.iiarjournals.org/content/45/4/1583

Nivolumab Plus 5-Fluorouracil/Leucovorin+Oxaliplatin for ... Survival outcomes remain poor in patients with AGC with severe PM, despite the introduction of NIVO+ FOLFOX. A prospective study of FOLFOX in a similar ...