Combination Therapies for Esophageal Cancer

Recruiting at 44 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Anticoagulants, NSAIDs, Antiplatelets, others

Disqualifiers: Squamous cancer, Severe dry eye, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

Duration: 60 weeks

90 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should not be on certain medications like NSAIDs, anticoagulants, or have received certain treatments recently. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination therapies for esophageal cancer?

Research shows that paclitaxel, a component of the combination therapy, has been effective in treating esophageal cancer, with a response rate of 32% and median survival of 13.2 months. Additionally, paclitaxel combined with ramucirumab is a standard second-line therapy for advanced gastroesophageal adenocarcinoma, indicating its potential effectiveness in similar conditions. ^{1 2 3 4 5}

Is the combination therapy of ramucirumab and paclitaxel safe for humans?

The combination of ramucirumab and paclitaxel has been studied for safety in patients with advanced gastric and esophageal cancers. Common side effects include fatigue, low white blood cell count (neutropenia), diarrhea, and nosebleeds (epistaxis). ^{1 5 6 7 8}

How is the drug MK-2870, Paclitaxel, and Ramucirumab combination unique for esophageal cancer?

This combination therapy is unique because it includes MK-2870, which is not commonly used in standard treatments for esophageal cancer, alongside paclitaxel and ramucirumab, which are known to be effective in other gastroesophageal cancers. The inclusion of MK-2870 may offer a novel approach by potentially enhancing the treatment's effectiveness or targeting the cancer differently. ^{4 5 9 10 11}

What is the purpose of this trial?

This is a phase 1/2 multicenter, open-label umbrella platform study that will evaluate the safety and efficacy of sacituzumab tirumotecan (MK-2870) plus paclitaxel versus ramucirumab plus paclitaxel, for the treatment of participants with advanced or metastatic gastric adenocarcinoma, gastroesophageal junction (GEJ) adenocarcinoma, or esophageal adenocarcinoma who have failed 1 prior line of therapy. This is an estimation study, and no formal hypothesis testing will be performed.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for people with advanced gastric, gastroesophageal junction, or esophageal adenocarcinoma who've had one prior treatment fail. They must have a life expectancy of at least 3 months and be in good physical condition (able to perform daily activities without significant limitations). Participants need to provide a tumor tissue sample and should not have HER2/neu positive cancer.

Inclusion Criteria

My side effects from past cancer treatments are mild or treated, except for hair loss or skin changes.

My doctor expects me to live at least 3 more months.

I have been previously treated for stomach, GEJ, or esophageal cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-In

Participants receive initial treatment to evaluate dose limiting toxicities and adverse events

4 weeks

2 visits (in-person)

Treatment

Participants receive MK-2870 plus paclitaxel or Ramucirumab plus paclitaxel for up to 60 weeks

60 weeks

Weekly visits (in-person) for 3 weeks, 1 week off

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 months

Treatment Details

Interventions

• MK-2870
• Paclitaxel
• Ramucirumab

Trial Overview The study compares the safety and effectiveness of MK-2870 combined with paclitaxel versus Ramucirumab with paclitaxel in patients whose first line of therapy didn't work. It's an open-label trial meaning everyone knows which treatment they're getting, but it won't test formal hypotheses.

Participant Groups

Group I: Sacituzumab Tirumotecan + Paclitaxel Experimental Treatment 3 Interventions

Following a 28-day run-in with sacituzumab tirumotecan at 3 mg/kg and 4 mg/kg IV infusion on Days 1 and 15 of a 6-week cycle plus paclitaxel at 80 mg/M\^2 IV infusion on days 1, 8 and 15 of a 4-week cycle, participants will receive paclitaxel at 80 mg/M\^2 IV infusion on days 1, 8, 15 of each 4-week cycle (3 weeks on and 1 week off) up to \~60 weeks plus sacituzumab tirumotecan at selected dose IV infusion on days 1, 15, 29 of every 6-week cycle until discontinuation.

Group II: Ramucirumab + Paclitaxel Active Control 2 Interventions

Participants will receive ramucirumab at 8mg/kg via intravenous (IV) infusion on days 1 and 15 of each 4-week cycle for up to \~60 weeks plus paclitaxel at 80 mg/M\^2 via IV infusion on Days 1, 8, and 15 of each 4-week cycle (3 weeks on and 1 week off) for up to \~60 weeks.

MK-2870 is already approved in China for the following indications:

Approved in China as Sacituzumab Tirumotecan for:

• Unresectable locally advanced or metastatic triple-negative breast cancer

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a study of 53 patients with advanced or recurrent esophageal cancer, weekly paclitaxel treatment resulted in an overall response rate of 44.2%, with a median overall survival of 10.4 months, indicating its efficacy as a treatment option.

While the treatment was generally manageable, it did lead to significant side effects, including neutropenia and leukopenia, with 34% of patients discontinuing treatment due to adverse events, but there were no treatment-related deaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of paclitaxel by weekly 1-h infusion for advanced or recurrent esophageal cancer in patients who had previously received platinum-based chemotherapy. Kato, K., Tahara, M., Hironaka, S., et al.[2022]

Preoperative chemoradiation therapy can improve survival rates in patients with adenocarcinoma of the esophagus, while it does not show the same benefit for those with squamous cell carcinoma, highlighting the importance of histology in treatment effectiveness.

Paclitaxel has demonstrated a 32% overall response rate and a median survival of 13.2 months in patients with advanced esophageal cancer, and its use in combination with radiation therapy and other drugs shows promise for enhancing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent paclitaxel and thoracic irradiation for locally advanced esophageal cancer. Blanke, CD., Choy, H., Teng, M., et al.[2015]

Weekly paclitaxel (PAC) chemotherapy is feasible as a second-line treatment for metastatic or recurrent esophageal cancer, based on a study of 6 patients.

While some patients experienced significant side effects like neutropenia and anemia, the treatment was manageable and allowed for outpatient administration, with 2 patients achieving stable disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Analysis of weekly paclitaxel chemotherapy for esophageal cancer]. Kawada, J., Nishimura, M., Matsui, Y., et al.[2015]

In a phase II trial involving 61 patients with advanced esophageal cancer, the combination of paclitaxel, cisplatin, and fluorouracil (5-FU) demonstrated significant antitumor activity, achieving a 48% overall response rate and a notable 20% complete response rate in patients with squamous cell carcinoma.

While the treatment showed substantial efficacy, it also resulted in severe but manageable toxicity, with 46% of patients requiring dose adjustments and 48% needing hospitalization due to side effects, highlighting the need for further optimization of dosing and scheduling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of paclitaxel, fluorouracil, and cisplatin in patients with advanced carcinoma of the esophagus. Ilson, DH., Ajani, J., Bhalla, K., et al.[2022]

In a phase II trial involving 111 patients with metastatic gastroesophageal adenocarcinoma, the combination of FOLFIRI and ramucirumab did not meet the primary endpoint of a 6-month overall survival rate of ≥65%, achieving only 54%.

While overall survival rates were similar between FOLFIRI plus ramucirumab and paclitaxel plus ramucirumab, FOLFIRI showed better objective response rates and progression-free survival, particularly in patients previously treated with docetaxel, suggesting potential for further investigation in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for patients with advanced or metastatic gastroesophageal adenocarcinoma with or without prior docetaxel - results from the phase II RAMIRIS Study of the German Gastric Cancer Study Group at AIO. Lorenzen, S., Thuss-Patience, P., Pauligk, C., et al.[2023]

The RAMIRIS trial is evaluating the effectiveness of a taxane-free chemotherapy regimen (FOLFIRI-Ram) compared to the standard taxane-based therapy (paclitaxel and ramucirumab) in patients with advanced gastro-esophageal adenocarcinoma (GEA) who have previously been treated with taxanes, with a total of 318 patients planned for the phase III study.

Preliminary results from the completed phase II trial indicated that FOLFIRI-Ram is feasible and effective, particularly for patients previously treated with docetaxel, showing better response rates and lower toxicity, which could lead to changes in treatment guidelines if confirmed in phase III.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab plus irinotecan / leucovorin / 5-FU versus ramucirumab plus paclitaxel in patients with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction, who failed one prior line of palliative chemotherapy: the phase II/III RAMIRIS study (AIO-STO-0415). Lorenzen, S., Schwarz, A., Pauligk, C., 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 1590 patients with metastatic gastric and lower esophageal adenocarcinoma, the combination of ramucirumab and paclitaxel used after the first line of chemotherapy was associated with improved overall survival (OS), indicating its efficacy in this patient population.

Factors such as younger age and lower comorbidity were linked to higher rates of palliative chemotherapy use, highlighting the need for further research to address disparities in treatment access, especially for patients in rural areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Ramucirumab Plus Paclitaxel Among Patients With Previously Treated Metastatic Gastric/Lower Esophageal Cancer: A Real-world Study. Abdel-Rahman, O., Mulder, K., Easaw, J.[2023]

In a randomized phase II trial involving 87 patients with metastatic esophageal or gastroesophageal junction cancers, the combination of paclitaxel and cixutumumab did not show a significant improvement in progression-free survival compared to paclitaxel alone, with median PFS of 2.6 months versus 2.3 months, respectively.

Both treatment arms were well tolerated, but the addition of cixutumumab did not enhance overall survival, which was 6.7 months for paclitaxel alone and 7.2 months for the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel With or Without Cixutumumab as Second-Line Treatment of Metastatic Esophageal or Gastroesophageal Junction Cancer: A Randomized Phase II ECOG-ACRIN Trial. Stockton, S., Catalano, P., Cohen, SJ., 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]

Paclitaxel is highly effective as a single agent for treating metastatic esophageal cancer, showing significant antitumor activity in various types of esophageal carcinomas.

Combining paclitaxel with cisplatin improves response rates, but adding 5-fluorouracil increases toxicity without providing additional clinical benefits, indicating the need for careful consideration in treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel in the treatment of esophageal cancer. Weiner, LM.[2015]

References

1. Germany pubmed.ncbi.nlm.nih.gov

A phase II study of paclitaxel by weekly 1-h infusion for advanced or recurrent esophageal cancer in patients who had previously received platinum-based chemotherapy. [2022]

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

Concurrent paclitaxel and thoracic irradiation for locally advanced esophageal cancer. [2015]

3. Japan pubmed.ncbi.nlm.nih.gov

[Analysis of weekly paclitaxel chemotherapy for esophageal cancer]. [2015]

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

Phase II trial of paclitaxel, fluorouracil, and cisplatin in patients with advanced carcinoma of the esophagus. [2022]

5. England pubmed.ncbi.nlm.nih.gov

FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for patients with advanced or metastatic gastroesophageal adenocarcinoma with or without prior docetaxel - results from the phase II RAMIRIS Study of the German Gastric Cancer Study Group at AIO. [2023]

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

Ramucirumab plus irinotecan / leucovorin / 5-FU versus ramucirumab plus paclitaxel in patients with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction, who failed one prior line of palliative chemotherapy: the phase II/III RAMIRIS study (AIO-STO-0415). [2023]

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

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

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

Outcomes of Ramucirumab Plus Paclitaxel Among Patients With Previously Treated Metastatic Gastric/Lower Esophageal Cancer: A Real-world Study. [2023]

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

Paclitaxel With or Without Cixutumumab as Second-Line Treatment of Metastatic Esophageal or Gastroesophageal Junction Cancer: A Randomized Phase II ECOG-ACRIN Trial. [2023]

10. China pubmed.ncbi.nlm.nih.gov

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

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

Paclitaxel in the treatment of esophageal cancer. [2015]