Combination Therapies for Esophageal Cancer

Recruiting at 55 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of two combination treatments for individuals with advanced stomach or esophageal cancer unresponsive to previous treatments. One group receives ramucirumab and paclitaxel, while the other receives sacituzumab tirumotecan (MK-2870) plus paclitaxel. The trial seeks participants diagnosed with advanced gastric or esophageal cancer who have experienced disease progression after prior treatment. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

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.

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

Research shows that the combination of sacituzumab tirumotecan and paclitaxel has been tested for safety in people with advanced cancers. Results indicate that this combination has an acceptable safety profile, with manageable side effects. In earlier tests, patients tolerated the treatment well without major issues.

Similarly, studies on the combination of ramucirumab and paclitaxel confirm its safety. Reported side effects were typical for this type of treatment and could be effectively managed.

Both treatment combinations have demonstrated safety for use in humans. While side effects can occur, they are generally manageable with proper medical care. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for esophageal cancer because they introduce innovative combination therapies that could enhance effectiveness compared to standard options like chemotherapy alone. The Ramucirumab + Paclitaxel arm combines a targeted therapy, ramucirumab, which inhibits blood vessel growth, with paclitaxel, a chemotherapy drug, potentially offering a dual approach to attack cancer cells and their supporting structures. The Sacituzumab Tirumotecan + Paclitaxel arm brings a novel antibody-drug conjugate, sacituzumab tirumotecan, which delivers a targeted attack to cancer cells, combined with paclitaxel for a comprehensive approach. These unique mechanisms may provide superior results by targeting cancer more precisely and reducing damage to healthy cells.

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

Research has shown that sacituzumab tirumotecan, a treatment under study in this trial, can fight tumors and is generally safe. Early results in patients with advanced cancers suggest it can reduce tumor size. This drug has also shown promise in treating other cancers, such as endometrial and ovarian. In this trial, researchers are testing sacituzumab tirumotecan in combination with paclitaxel, a well-known chemotherapy drug that stops cancer cells from growing, in one treatment arm. Another arm of this trial will test the combination of ramucirumab and paclitaxel. Together, these drugs could offer new treatment options for people with esophageal cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

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 doctor expects me to live at least 3 more months.

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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 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]

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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06356311

A Study to Evaluate Sacituzumab Tirumotecan (MK-2870) ... This study will compare how safe and effective sacituzumab tirumotecan is versus the treatment of physician's choice (TPC) in participants with advanced/ ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.TPS511

KEYMAKER-U06: Phase 1/2 umbrella platform study of ... Substudy 06D (NCT06445972) will be conducted to evaluate sacituzumab tirumotecan plus paclitaxel as second-line therapy for patients with ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12142944/

Results of a phase 1/2 study of sacituzumab tirumotecan in ... Sac-TMT demonstrated manageable safety profile in patients with unresectable locally advanced/metastatic solid tumors and promising antitumor ...

4. ucla.clinicaltrials.researcherprofiles.org ucla.clinicaltrials.researcherprofiles.org/esophageal-cancer

UCLA Esophageal Cancer Clinical Trials — Los Angeles This study will compare how safe and effective sacituzumab tirumotecan is versus the treatment of physician's choice (TPC) in participants ...

5. onclive.com onclive.com/view/sacituzumab-tirumotecan-shows-antitumor-activity-in-previously-treated-endometrial-ovarian-cancers

Sacituzumab Tirumotecan Shows Antitumor Activity in ... Sacituzumab tirumotecan monotherapy demonstrated antitumor activity with a manageable safety profile in previously treated endometrial and ovarian cancers.

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

Real-world efficacy and toxicity data of paclitaxel and ... Despite the confirmed clinical benefit of paclitaxel and ramucirumab combination, there are no data indicating the superiority of this combination over ...

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

a randomised, multicentre, double-blind, phase 3 trial Median overall survival was 8·71 months (95% CI 7·98-9·49) in the ramucirumab plus paclitaxel group and 7·92 months (6·31-9·10) in the placebo plus paclitaxel ...

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

Ramucirumab plus paclitaxel as switch maintenance ... We aimed to assess whether switch maintenance or early second-line therapy with paclitaxel plus ramucirumab improved outcomes compared with ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e16043

Paclitaxel + ramucirumab versus paclitaxel alone in ... Primary endpoint was overall survival rate at 6months (mos) (OS@6), main secondary endpoints were OS, PFS, objective response rate (ORR) and ...

10. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2814208

Ramucirumab, Avelumab, and Paclitaxel as Second-Line ... Paclitaxel and ramucirumab achieved an OS rate at 6 months of 66% in the Western population of the Rainbow trial. We expected worse prognostic ...