Combination Therapy for Esophageal and Stomach Cancers

Recruiting at 6 trial locations

Overseen By Yelena Janjigian, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Ramucirumab, Paclitaxel, Docetaxel, others

Disqualifiers: Immunodeficiency, Active tuberculosis, Active hepatitis, 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: Unknown

Duration: up to 2 years

37 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of new and existing drugs to treat patients whose disease isn't responding well to standard treatments. The drugs work by either boosting the immune system or directly attacking cancer cells. The goal is to find more effective treatment options for these patients.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received certain treatments like ramucirumab or paclitaxel recently, and you should not be on systemic steroid therapy or other immunosuppressive treatments within 7 days before starting the trial.

What data supports the effectiveness of the drug combination therapy for esophageal and stomach cancers?

Research shows that ramucirumab, when used with paclitaxel, has been effective in increasing survival in patients with advanced gastric cancer, which is similar to stomach cancer. This suggests potential effectiveness for the combination therapy in treating esophageal and stomach cancers. ^{1 2 3 4 5}

Is the combination therapy involving ramucirumab and paclitaxel generally safe for humans?

The combination of ramucirumab and paclitaxel has been studied in patients with advanced gastric cancer and is generally considered safe, with common side effects including high blood pressure and diarrhea. In clinical trials, this combination did not result in any dose-limiting toxicities, meaning it was well tolerated at the tested doses. ^{1 4 6 7 8}

What makes the combination therapy for esophageal and stomach cancers unique?

This combination therapy is unique because it includes a mix of biologic agents and chemotherapy drugs, such as Balstilimab and Botensilimab, which are immunomodulators (drugs that modify the immune system), along with Paclitaxel and Ramucirumab, which have shown effectiveness in improving survival in gastric cancer. This approach targets multiple pathways in cancer cells, potentially offering a more comprehensive treatment compared to standard therapies that typically focus on fewer targets. ^{5 9 10 11 12}

Research Team

Yelena Janjigian, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for individuals with certain types of cancer affecting the stomach, esophagus, or where they join together. Specific details on who can join are not provided here, but typically participants would need to meet certain health standards and have a diagnosis that matches the trial's focus.

Inclusion Criteria

My cancer has worsened after one treatment for its advanced stage.

My cancer can be measured or evaluated for treatment response.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

I have been treated with ramucirumab before.

I have had a gastrointestinal perforation or fistula.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive study treatment with agenT-797, botensilimab, balstilimab, ramucirumab, and paclitaxel. The start of each agent depends on disease impact.

up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• agenT-797
• Balstilimab
• Botensilimab
• Paclitaxel
• Ramucirumab

Trial Overview The study is testing a combination of treatments: agenT-797, botensilimab, balstilimab, ramucirumab, and paclitaxel in patients with esophageal or gastric cancers. The timing of each treatment may vary based on individual patient needs.

Participant Groups

Group I: Participants diagnoses with Esophageal, Gastric, or Gastro-esophageal Junction Cancer Experimental Treatment 5 Interventions

Participants with measurable disease and with evaluable disease as defined by RECIST v1.1 will be enrolled on this study.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

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]

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]

Ramucirumab, both as a monotherapy and in combination with paclitaxel, was evaluated for treating advanced gastric cancer, but the NICE committee found it to be not cost-effective, with incremental cost-effectiveness ratios (ICERs) significantly above acceptable thresholds (e.g., £188,100 per QALY for monotherapy).

Despite showing some clinical effectiveness, neither ramucirumab alone nor in combination with paclitaxel met the criteria for cost-effectiveness as they did not provide a meaningful extension of life (less than 3 months), leading to the conclusion that these treatments could not be recommended for use in the NHS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab for Treating Advanced Gastric Cancer or Gastro-Oesophageal Junction Adenocarcinoma Previously Treated with Chemotherapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. Büyükkaramikli, NC., Blommestein, HM., Riemsma, R., et al.[2023]

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]

Biologic therapies, particularly those targeting HER2 and VEGF, are showing promise in treating esophageal and gastric cancers, with trastuzumab and ramucirumab currently recommended by the NCCN for specific patient groups.

Recent studies indicate that other agents like pertuzumab, apatinib, and pembrolizumab may improve overall and progression-free survival, suggesting a growing role for targeted biologic therapies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. Samson, P., Lockhart, AC.[2020]

The combination of ramucirumab and paclitaxel as second-line therapy in Japanese patients with metastatic gastric adenocarcinoma was found to be safe and well-tolerated, with no dose-limiting toxicities reported in a phase Ib study involving 6 patients.

Patients experienced stable disease or partial response, with a median treatment duration of approximately 12.5 weeks, indicating potential efficacy of this treatment regimen in managing advanced gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase ib study of safety and pharmacokinetics of ramucirumab in combination with paclitaxel in patients with advanced gastric adenocarcinomas. Ueda, S., Satoh, T., Gotoh, M., 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 involving 538 patients with advanced gastric or gastroesophageal junction adenocarcinoma, ramucirumab plus paclitaxel significantly improved progression-free survival and objective response rates compared to placebo plus paclitaxel in both Japanese and Western populations.

While the combination treatment had a higher incidence of grade 3 or higher adverse events, particularly neutropenia, the overall safety profiles were similar across populations, indicating that ramucirumab plus paclitaxel is an effective option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subgroup analyses of the safety and efficacy of ramucirumab in Japanese and Western patients in RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer. Shitara, K., Muro, K., Shimada, Y., et al.[2023]

In a phase II trial involving 30 patients with advanced esophageal cancer, the combination of paclitaxel and cisplatin resulted in a significant anti-tumor response, with 59.3% of patients showing major objective responses, including 5 complete responses.

The treatment was associated with manageable toxicity, primarily alopecia and grade 3 to 4 neutropenia in 17.9% of patients, suggesting that this regimen can be a viable option for patients with advanced esophageal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase II study of paclitaxel and cisplatin for advanced squamous-cell carcinoma of esophagus]. Huang, J., Cai, RG., Meng, PJ., et al.[2015]

The combination of paclitaxel, etoposide, and cisplatin (TPE) demonstrated high efficacy in treating locally advanced gastric and gastroesophageal carcinoma, with all 22 evaluable patients responding to the treatment, including 3 complete responders and 19 partial responders.

Despite significant hematologic toxicity, including Grade 3 anemia and neutropenia in all patients, the median survival was 12.5 months, suggesting that TPE chemotherapy is a promising regimen that warrants further investigation in Phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined paclitaxel, cisplatin, and etoposide for patients with previously untreated esophageal and gastroesophageal carcinomas. Lokich, JJ., Sonneborn, H., Anderson, NR., et al.[2019]

Key chemotherapy drugs for gastroesophageal cancer include fluoropyrimidine, platinum, taxanes, and irinotecan, with concurrent chemoradiotherapy being a primary treatment approach, especially for esophageal cancer.

Targeted therapies like trastuzumab for HER2-positive gastric cancer and ramucirumab combined with paclitaxel have been shown to improve patient survival, while anti-PD-1 antibodies are now available for later-line treatment, highlighting the importance of molecular profiling in optimizing therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent progress of chemotherapy and biomarkers for gastroesophageal cancer. Maeda, O., Ando, Y.[2020]

Esophageal cancer, particularly adenocarcinoma, is increasingly common, with over half of patients presenting with metastatic disease, making palliative chemotherapy a crucial treatment option.

Recent studies show that weekly irinotecan and cisplatin is a highly effective and less toxic regimen for treating both adenocarcinoma and squamous cell carcinoma, while paclitaxel also shows promise with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in esophageal cancer. Enzinger, PC., Ilson, DH., Kelsen, DP.[2022]

References

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

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

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

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

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

Ramucirumab for Treating Advanced Gastric Cancer or Gastro-Oesophageal Junction Adenocarcinoma Previously Treated with Chemotherapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. [2023]

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

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

5. China pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. [2020]

6. England pubmed.ncbi.nlm.nih.gov

A phase ib study of safety and pharmacokinetics of ramucirumab in combination with paclitaxel in patients with advanced gastric adenocarcinomas. [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

Subgroup analyses of the safety and efficacy of ramucirumab in Japanese and Western patients in RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer. [2023]

9. China pubmed.ncbi.nlm.nih.gov

[Phase II study of paclitaxel and cisplatin for advanced squamous-cell carcinoma of esophagus]. [2015]

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

Combined paclitaxel, cisplatin, and etoposide for patients with previously untreated esophageal and gastroesophageal carcinomas. [2019]

11. China pubmed.ncbi.nlm.nih.gov

Recent progress of chemotherapy and biomarkers for gastroesophageal cancer. [2020]

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

Chemotherapy in esophageal cancer. [2022]