TRK-950 + Ramucirumab + Paclitaxel for Stomach Cancer

Recruiting at 23 trial locations

Overseen By (US sites) Contact for Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Toray Industries, Inc

Must be taking: Ramucirumab, Paclitaxel

Must not be taking: Anticoagulants

Disqualifiers: Congestive heart failure, Pneumonitis, 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: 1

Duration: 24 months

146 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug, TRK-950, combined with two existing cancer drugs in patients with a specific type of stomach cancer. The goal is to see if this combination can better control cancer growth and improve survival compared to the existing treatments alone.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had certain treatments like chemotherapy or radiation therapy within a few weeks before starting the trial.

What data supports the effectiveness of the drug combination TRK-950, Ramucirumab, and Paclitaxel for stomach cancer?

Research shows that Ramucirumab, when used alone or with Paclitaxel, significantly improves survival in patients with advanced stomach cancer. This combination has been shown to be effective in prolonging life and slowing disease progression in clinical trials. ^{1 2 3 4 5}

Is the combination of TRK-950, Ramucirumab, and Paclitaxel safe for treating stomach cancer?

The combination of Ramucirumab and Paclitaxel has been studied for stomach cancer, showing an acceptable safety profile. Common side effects include high blood pressure, fatigue, and low white blood cell counts, which require careful monitoring. ^{1 2 6 7 8}

What makes the TRK-950 + Ramucirumab + Paclitaxel drug unique for stomach cancer?

The combination of TRK-950 with Ramucirumab and Paclitaxel is unique because it adds a novel component (TRK-950) to an already established second-line treatment (Ramucirumab and Paclitaxel) for advanced gastric cancer, potentially enhancing effectiveness or offering new benefits. ^{2 5 8 9 10}

Eligibility Criteria

This trial is for adults with advanced gastric or gastro-esophageal junction adenocarcinoma that has worsened after first-line therapy. They must be fit enough for second-line treatment, have a life expectancy of at least 3 months, and measurable disease on scans. Participants need to function well daily (ECOG 0-1) and have good organ function.

Inclusion Criteria

My recent tests show my organs are functioning well.

My cancer has worsened or spread during or after my first treatment.

I am at least 18 years old in the US or Japan, or 19 in Korea.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TRK-950 in combination with ramucirumab and paclitaxel, or ramucirumab and paclitaxel alone, in 28-day cycles

24 months

Visits on Days 1, 8, 15, and 22 of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

45 days

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Paclitaxel
• Ramucirumab
• TRK-950

Trial Overview The study tests TRK-950 combined with Ramucirumab and Paclitaxel against just Ramucirumab and Paclitaxel in patients with stomach cancer. It aims to find the best dose of TRK-950, check its safety, effectiveness, and how the body reacts to it (antibody development).

Participant Groups

Group I: Arm B: TRK-950(10 mg/kg)+Ramucirumab+Paclitaxel Experimental Treatment 3 Interventions

Participants who will be randomized to receive a 10 mg/kg intravenous(IV) dose of TRK-950 on days 1, 8, 15 and 22 in combination with 8 mg/kg IV dose of ramucirumab on days 1 and 15 and 80 mg/m\^2 IV dose of paclitaxel on Days 1, 8, and 15 of a 28-day cycle.

Group II: Arm A: TRK-950(5 mg/kg)+Ramucirumab+Paclitaxel Experimental Treatment 3 Interventions

Participants who will be randomized to receive a 5 mg/kg intravenous(IV) dose of TRK-950 on days 1, 8, 15 and 22 in combination with 8 mg/kg IV dose of ramucirumab on days 1 and 15 and 80 mg/m\^2 IV dose of paclitaxel on Days 1, 8, and 15 of a 28-day cycle.

Group III: Arm C: Ramucirumab+Paclitaxel Active Control 2 Interventions

Participants who will be randomized to receive a 8 mg/kg IV dose of ramucirumab on Days 1 and 15 in combination with 80 mg/m\^2 IV dose of paclitaxel on Days 1, 8, and 15 of a 28-day cycle.

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?

Toray Industries, Inc

Lead Sponsor

Trials

22

Recruited

2,400+

Headquarters

Japan

Known For

Gene Therapies

Top Products

FERON™, DORNER™, REMITCH™

Findings from Research

Ramucirumab significantly improves overall survival and progression-free survival in adults with advanced gastric or gastro-oesophageal junction adenocarcinoma, based on results from two phase III trials (REGARD and RAINBOW) involving patients treated with 8 mg/kg every 2 weeks.

The treatment is generally well-tolerated, with hypertension being the most common serious side effect, making ramucirumab a valuable second-line therapy option for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab: A Review in Advanced Gastric Cancer. Greig, SL., Keating, GM.[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 (Cyramza) is a significant advancement in the treatment of gastric cancer, targeting the vascular endothelial growth factor receptor 2 (VEGFR-2) to inhibit tumor blood supply.

Clinical studies have demonstrated that ramucirumab improves overall survival in patients with advanced gastric cancer, making it a crucial option for those with this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab (Cyramza): A Breakthrough Treatment for Gastric Cancer. Singh, AD., Parmar, S.[2020]

In a study of 42 patients with advanced gastric cancer treated with taxanes and ramucirumab, the median overall survival was found to be 11.8 months, indicating a significant impact of this treatment regimen on patient longevity.

The analysis revealed that a better disease control rate was associated with improved survival, while the presence of peritoneal metastasis was linked to a higher risk of mortality, highlighting the importance of clinical response in predicting outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Second-line Chemotherapy on Prognosis: Response of Advanced Gastric Cancer to Taxanes Plus Ramucirumab. Masuda, Y., Kananazawa, Y., Matsuno, K., et al.[2023]

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]

Ramucirumab significantly improved overall survival in patients with advanced gastric or gastroesophageal junction adenocarcinoma, both as a monotherapy (355 patients) and in combination with paclitaxel (665 patients), with hazard ratios of 0.78 and 0.81, respectively.

The most common side effects reported were hypertension and diarrhea for the monotherapy, and fatigue, neutropenia, diarrhea, and epistaxis for the combination therapy, indicating a manageable safety profile but with notable adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Ramucirumab for Gastric Cancer. Casak, SJ., Fashoyin-Aje, I., Lemery, SJ., et al.[2023]

In a study of 11 patients with unresectable and recurrent gastric cancer, the combination of Ramucirumab (RAM) and paclitaxel (PTX) demonstrated efficacy, with a 90.9% disease control rate and a median overall survival of 20.8 months.

The treatment was found to be safe, with no serious adverse events reported, and it was effective across different age groups, indicating its feasibility for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical usefulness of ramucirumab plus paclitaxel for unresectable and recurrent gastric cancer. Hayase, S., Yamada, L., Ujiie, D., et al.[2023]

In a study of 33 patients with advanced gastric cancer, the combination of paclitaxel (PTX) and ramucirumab (RAM) showed a disease control rate of 66.7% and a median overall survival of 9.3 months, indicating its efficacy as a treatment option for unresectable or recurrent cases.

Despite the promising results, 85% of patients experienced grade 3/4 adverse events, highlighting the need for careful monitoring and management of side effects, especially in older patients or those with poorer performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Paclitaxel plus Ramucirumab Therapy for Unresectable or Recurrent Gastric Cancer]. Tsujio, G., Toyokawa, T., Fukuoka, T., et al.[2023]

In a study of 66 patients with advanced gastric cancer receiving weekly paclitaxel and ramucirumab therapy, 31.8% experienced severe neutropenia, highlighting the need for careful monitoring in this population.

Prior treatment with oxaliplatin-containing regimens and elevated total bilirubin levels were identified as significant risk factors for developing severe neutropenia and febrile neutropenia, which can impact overall survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prior treatment with oxaliplatin-containing regimens and higher total bilirubin levels are risk factors for neutropenia and febrile neutropenia in patients with gastric or esophagogastric junction cancer receiving weekly paclitaxel and ramucirumab therapy: a single center retrospective study. Nara, K., Yamamoto, T., Yamashita, 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Ramucirumab: A Review in Advanced Gastric Cancer. [2023]

2. Japan pubmed.ncbi.nlm.nih.gov

[Clinical Experience of Ramucirumab for Treating Advanced Gastric Cancer]. [2023]

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

Ramucirumab (Cyramza): A Breakthrough Treatment for Gastric Cancer. [2020]

4. Greece pubmed.ncbi.nlm.nih.gov

Impact of Second-line Chemotherapy on Prognosis: Response of Advanced Gastric Cancer to Taxanes Plus Ramucirumab. [2023]

5. France pubmed.ncbi.nlm.nih.gov

Ramucirumab as Second-Line Therapy in Metastatic Gastric Cancer: Real-World Data from the RAMoss Study. [2023]

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

FDA Approval Summary: Ramucirumab for Gastric Cancer. [2023]

7. Japan pubmed.ncbi.nlm.nih.gov

Clinical usefulness of ramucirumab plus paclitaxel for unresectable and recurrent gastric cancer. [2023]

8. Japan pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Paclitaxel plus Ramucirumab Therapy for Unresectable or Recurrent Gastric Cancer]. [2023]

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

Prior treatment with oxaliplatin-containing regimens and higher total bilirubin levels are risk factors for neutropenia and febrile neutropenia in patients with gastric or esophagogastric junction cancer receiving weekly paclitaxel and ramucirumab therapy: a single center retrospective study. [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

Placental growth factor is a predictive biomarker for ramucirumab treatment in advanced gastric cancer. [2023]