Ramucirumab + Trifluridine/Tipiracil or Paclitaxel for Gastric Cancer

Recruiting at 7 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Academic and Community Cancer Research United

Must not be taking: Antiplatelets, Antiretrovirals

Disqualifiers: Pregnancy, Severe disease, Recent surgery, 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: 31

Duration: Up to 36 cycles (approximately 3 years)

116 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two different treatment combinations for gastric or gastroesophageal cancer that has spread and been previously treated. One group receives ramucirumab with a chemotherapy pill called trifluridine/tipiracil, while the other group receives ramucirumab with paclitaxel, a chemotherapy drug that stops cell division. The goal is to determine if these treatments can effectively target and damage cancer cells. Individuals with advanced stomach or gastroesophageal cancer who have not responded well to standard chemotherapy might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on warfarin, you must switch to low molecular weight heparin before starting the trial. Also, if you are on full-dose anticoagulation, you need to be on a stable dose for at least 14 days before starting the trial.

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

Research has shown that both treatment combinations under study are considered safe. In earlier studies, the combination of trifluridine/tipiracil with ramucirumab was generally well-tolerated by many patients, with no unexpected side effects causing major safety concerns.

Similarly, researchers have widely studied the combination of paclitaxel and ramucirumab. Evidence suggests that this combination is usually well-tolerated and effective in treating advanced stomach cancer. Most side effects were manageable and similar to those seen with other cancer treatments.

Overall, both treatment combinations have been researched in different settings and are deemed safe enough for further study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for gastric cancer because they offer unique approaches compared to standard therapies. Ramucirumab, when combined with Trifluridine/Tipiracil (TAS-102), targets the VEGF receptor, which can help inhibit tumor blood vessel growth—a different mechanism compared to standard chemotherapy. Trifluridine/Tipiracil also introduces a novel oral chemotherapy component that disrupts cancer cell DNA, potentially offering a new line of attack. The combination with paclitaxel, a chemotherapy drug that interferes with cell division, further enhances the treatment by adding a powerful, well-known agent to the mix, increasing the potential for effectiveness against resistant cancer cells.

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

Studies have shown that combining paclitaxel and ramucirumab effectively treats advanced stomach cancer. This combination is recommended as a second-line option when the first treatment fails and has been linked to a longer period, about 6.6 months, during which the cancer does not worsen, compared to 3.5 months with other treatments. In this trial, some participants will receive this combination.

Other participants will receive a combination of trifluridine/tipiracil with ramucirumab. Research suggests this combination might help fight tumors, although results are mixed, with some studies showing only a small improvement in overall survival. This trial studies both treatment combinations for their potential to manage advanced stomach cancer effectively. ^{1 4 5 6 7}

Who Is on the Research Team?

Mohamad B Sonbol

Principal Investigator

Academic and Community Cancer Research United

Are You a Good Fit for This Trial?

Adults with advanced gastric or gastroesophageal junction cancer that has worsened within 6 months after treatment can join. They must have had prior chemotherapy, be in good physical condition, and able to take oral meds. Pregnant women, nursing mothers, those with recent serious health issues like heart attacks or uncontrolled hypertension are excluded.

Inclusion Criteria

Hemoglobin >= 9.0 g/dL (obtained =< 7 days prior to registration)

Aspartate transaminase (AST) and alanine transaminase (ALT) =< 3 x ULN ( =< 5.0 x UNL, if with liver metastasis) (obtained =< 7 days prior to registration)

My advanced cancer has worsened within 6 months after my last treatment.

Exclusion Criteria

I understand the study drug's effects on unborn babies are unknown.

I have been treated with TAS-102 or ramucirumab before.

I received taxane therapy less than 6 months ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive either TAS-102 and ramucirumab or paclitaxel and ramucirumab. Treatment repeats every 28 days for up to 36 cycles.

Up to 36 cycles (approximately 3 years)

Visits on days 1, 8, and 15 of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

3 years

Follow-up at 30-35 days post-treatment, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Paclitaxel
• Ramucirumab
• Trifluridine and Tipiracil Hydrochloride

Trial Overview The trial is testing the effectiveness of ramucirumab combined with either trifluridine/tipiracil or paclitaxel in patients who've already been treated for advanced stomach cancers. Ramucirumab targets blood vessel growth in tumors while the other drugs aim to damage tumor DNA or block cell growth.

How Is the Trial Designed?

Group I: Arm A (TAS-102, ramucirumab) Experimental Treatment 3 Interventions

Patients receive TAS-102 PO BID on days 1-5 and 8-12, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (paclitaxel, ramucirumab) Active Control 3 Interventions

Patients receive paclitaxel IV over 1-96 hours on days 1, 8, and 15, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in European Union as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in Canada as Paclitaxel for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Who Is Running the Clinical Trial?

Academic and Community Cancer Research United

Lead Sponsor

Trials

54

Recruited

4,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase 2 study involving 64 patients with advanced gastric cancer, the combination of trifluridine/tipiracil and ramucirumab demonstrated a high disease control rate of 85% in patients previously treated with one line of chemotherapy and 77% in those treated with two to four lines, indicating strong clinical activity.

The treatment was generally well-tolerated, with serious adverse events occurring in only three patients from the cohort treated with one prior chemotherapy, while no serious treatment-related adverse events were reported in the cohort with more extensive prior treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of trifluridine/tipiracil and ramucirumab in previously treated advanced gastric cancer: an open-label, single-arm, phase 2 trial. Kawazoe, A., Ando, T., Hosaka, H., et al.[2023]

In a study of 26 patients with advanced gastric cancer, high levels of placental growth factor (PlGF) were associated with poor treatment outcomes for ramucirumab (RAM), indicating that PlGF expression could serve as a predictive biomarker for RAM efficacy.

Patients with low PlGF levels had a 50% overall response rate to RAM treatment, while those with high PlGF levels showed no response, suggesting that targeting PlGF may enhance the effectiveness of RAM therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placental growth factor is a predictive biomarker for ramucirumab treatment in advanced gastric cancer. Natsume, M., Shimura, T., Iwasaki, H., et al.[2023]

In a study of 101 advanced gastric cancer patients, the combination of trifluridine/tipiracil and ramucirumab showed a higher objective response rate (13.5%) and disease control rate (64.9%) compared to trifluridine/tipiracil alone (3.8% and 42.3%, respectively).

Patients receiving the combination treatment also experienced significantly longer median progression-free survival (3.0 months vs. 1.8 months) and overall survival (7.2 months vs. 3.8 months), indicating that this combination therapy may be more effective than monotherapy without unexpected adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of trifluridine/tipiracil plus ramucirumab in comparison with trifluridine/tipiracil monotherapy for patients with advanced gastric cancer-single institutional experience. Okunaka, M., Kawazoe, A., Nakamura, H., et al.[2023]

In a study of 23 advanced gastric cancer patients, those treated with ramucirumab (RAM) plus paclitaxel (PTX) showed a higher overall response rate (30%) and longer progression-free survival (187 days) compared to those treated with RAM alone (10% response rate and 54 days progression-free survival).

Both treatment regimens were found to be safe for outpatient administration, with fewer severe hematological adverse events in the RAM group (1 case) compared to the PTX+RAM group (6 cases), indicating that while combination therapy may be more effective, it also carries a higher risk of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Experience of Ramucirumab for Treating Advanced Gastric Cancer]. Kimura, Y., Makari, Y., Mikami, J., et al.[2023]

Ramucirumab, a monoclonal antibody targeting VEGFR-2, has been shown to be safe and effective for patients with advanced gastric cancer, particularly when combined with paclitaxel.

However, there is a risk of serious adverse events, such as gastrointestinal perforation, as demonstrated in a case of a 67-year-old man who developed this complication after treatment, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of ramucirumab-related gastrointestinal perforation in gastric cancer with small bowel metastasis. Urakawa, S., Sakai, D., Miyazaki, Y., et al.[2020]

Trifluridine/tipiracil (Lonsurf®) has been shown to significantly improve overall survival in patients with metastatic gastric cancer who have previously undergone at least two treatment regimens, as demonstrated in the phase III TAGS trial.

The treatment not only enhances survival and progression-free survival but also maintains health-related quality of life, with manageable side effects primarily related to blood cell counts and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trifluridine/Tipiracil: A Review in Metastatic Gastric Cancer. Kang, C., Dhillon, S., Deeks, ED.[2020]

Trifluridine/tipiracil (TAS-102) has been approved for treating metastatic gastric and gastroesophageal junction adenocarcinoma after showing significant improvement in overall survival (5.7 months) compared to placebo (3.6 months) in a Phase III trial with patients who had undergone at least two lines of chemotherapy.

The treatment demonstrated a disease control rate of over 50% after eight weeks and did not impair quality of life, while the most common serious side effect was neutropenia, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Evaluation of the Safety and Efficacy of Trifluridine/Tipiracil in the Treatment of Advanced Gastric/Gastroesophageal Junction Adenocarcinoma: Evidence to Date. Wheelden, M., Yee, NS.[2020]

In a study involving 167 patients with advanced gastric cancer, ramucirumab was found to be well tolerated, with a low incidence of severe toxicity (9.6%) and only 3% of patients discontinuing treatment due to adverse effects.

The treatment showed a 20.2% overall response rate and a median overall survival of 8.0 months, indicating that ramucirumab is effective in a real-life setting, consistent with results from previous randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab as Second-Line Therapy in Metastatic Gastric Cancer: Real-World Data from the RAMoss Study. Di Bartolomeo, M., Niger, M., Tirino, G., et al.[2023]

Trifluridine/tipiracil is an effective oral chemotherapy for patients with advanced gastric cancer who have not responded to standard treatments, showing improved survival rates in heavily pretreated patients.

The therapy has been approved in multiple regions, including the U.S., Japan, and the EU, and is currently being studied in combination with other treatments, indicating its potential as a key option in gastric cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trifluridine/tipiracil for the treatment of metastatic gastric cancer. Kawazoe, A., Shitara, K.[2020]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2949819824000347

Real-world efficacy and toxicity data of paclitaxel and ... Paclitaxel/ramucirumab is an effective treatment in patients with advanced gastric cancer. •. The superiority of this regimen over alternative therapeutic ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8450614/

Ramucirumab plus paclitaxel as second-line treatment in ... The Korean Gastric Cancer Treatment Guidelines recommend ramucirumab plus paclitaxel as a second-line treatment for advanced gastric or GEJ ...

3. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00580-1/abstract

Ramucirumab plus paclitaxel as switch maintenance ... Paclitaxel and ramucirumab switch maintenance could be a potential treatment strategy in patients with advanced HER2-negative gastric or gastro- ...

4. onclive.com onclive.com/view/switch-ramucirumab-paclitaxel-maintenance-yields-favorable-outcomes-in-her2-gastric-cancer

Switch Ramucirumab/Paclitaxel Maintenance Yields ... Ramucirumab plus paclitaxel improved median PFS to 6.6 months vs 3.5 months with continued FOLFOX/CAPOX. · Median OS was 12.6 months with ...

5. nature.com nature.com/articles/s41598-025-13714-9

Efficacy and safety of taxane plus ramucirumab for ... Based on our study, there were no significant differences in efficacy and adverse events between PTX plus RAM and nab-PTX plus RAM, suggesting ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34626550/

a randomised, multicentre, double-blind, phase 3 trial Background: In the global phase 3 RAINBOW study, ramucirumab plus paclitaxel significantly improved overall survival compared with placebo plus paclitaxel in ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06666582

Real-world Data of Paclitaxel and Ramucirumab ... Our aim was to evaluate whether second-line treatment with paclitaxel and ramucirumab was associated with improved clinical outcomes compared to ...