Combination Therapies for Esophageal Cancer
Recruiting in Palo Alto (17 mi)
+37 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Merck Sharp & Dohme LLC
Must not be taking: Anticoagulants, NSAIDs, Antiplatelets, others
Disqualifiers: Squamous cancer, Severe dry eye, others
No Placebo Group
Trial Summary
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 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.
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.12345
Is the combination therapy of ramucirumab and paclitaxel safe for humans?
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.4591011
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.
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Trial 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 (Other)
- Paclitaxel (Other)
- Ramucirumab (Monoclonal Antibodies)
Trial OverviewThe 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
2Treatment groups
Experimental Treatment
Active Control
Group I: MK-2870 + PaclitaxelExperimental Treatment2 Interventions
Following a 28-day run-in with MK-2870 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 MK-2870 at selected dose IV infusion on days 1, 15, 29 of every 6-week cycle until discontinuation.
Group II: Ramucirumab + PaclitaxelActive Control2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cancer and Hematology Centers of Western Michigan ( Site 8912)Grand Rapids, MI
Hematology-Oncology Associates of Central NY, P.C. ( Site 8925)East Syracuse, NY
University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 8927)Tucson, AZ
Norton Cancer Institute - Downtown ( Site 8900)Louisville, KY
More Trial Locations
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Who Is Running the Clinical Trial?
Merck Sharp & Dohme LLCLead Sponsor
References
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]To evaluate the efficacy and safety of weekly paclitaxel (Taxol(®)) in patients with advanced or recurrent esophageal cancer.
Concurrent paclitaxel and thoracic irradiation for locally advanced esophageal cancer. [2015]Esophageal cancer is a major cause of morbidity and mortality worldwide. Although patients often present with apparently resectable disease, systemic spread frequently occurs before the development of symptoms and detection of tumor. The use of combined chemoradiation therapy, particularly before resection, appears to prolong survival and increase cure rates in certain histologic subtypes. Four randomized phase III trials compared preoperative chemoradiotherapy plus surgery with surgery alone. In trials including only patients with squamous histology, no improvement in survival was observed with preoperative chemoradiation therapy; however, in a trial including only patients with adenocarcinoma histology, improved median and overall survival were observed. Paclitaxel has been evaluated as a single agent in a phase II trial in previously untreated patients with locally advanced unresectable or metastatic esophageal cancer; the overall response rate was 32% and median survival was 13.2 months. Paclitaxel-based combinations also have been evaluated in esophageal cancer; particularly encouraging preliminary results have been achieved with paclitaxel/cisplatin/5-fluorouracil. Because paclitaxel is a potent radiosensitizer, it also has been evaluated in combination with radiation therapy for esophageal and other thoracic cancers, alone and in combination with other chemotherapeutic agents. Preliminary results suggest that neoadjuvant therapy with paclitaxel-based combinations (including 5-fluorouracil and cisplatin) and radiation is highly active, with variable toxicity. A goal of future trials is to assess paclitaxel-based combined modality therapy in combination with other new chemotherapeutic agents.
[Analysis of weekly paclitaxel chemotherapy for esophageal cancer]. [2015]Public knowledge-based application for paclitaxe(l PAC) has been approved for advanced or recurrent esophageal cancer. We investigated the feasibility of weekly PAC chemotherapy as a second-line or subsequent regimen for metastatic or recurrent esophageal cancer.
Phase II trial of paclitaxel, fluorouracil, and cisplatin in patients with advanced carcinoma of the esophagus. [2022]We have previously identified paclitaxel as an active single agent in the treatment of esophageal cancer. We performed a phase II trial of paclitaxel in combination with cisplatin and fluorouracil (5-FU), conventionally used chemotherapy for esophageal cancer. The antitumor response, toxicity, and survival of patients treated with the three-drug regimen were evaluated.
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]Ramucirumab and paclitaxel is the standard second-line therapy in patients with metastatic gastroesophageal adenocarcinoma. We report the efficacy and safety analyses of FOLFIRI and ramucirumab versus paclitaxel and ramucirumab after the failure of a platinum- and fluoropyrimidine-containing chemotherapy.
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]Paclitaxel in combination with ramucirumab is the standard of care second-line therapy in gastro-esophageal adenocarcinoma (GEA). As the number of taxane pretreated patients in the perioperative or first-line setting is increasing, it is unknown whether these patients benefit from re-applying a taxane in using the combination of paclitaxel and ramucirumab. Furthermore, the rates of neurotoxicity with first-line FOLFOX or FLOT range from 30%-70%, making second-line taxane-containing therapy less suitable to a meaningful portion of patients. This patient group is likely to benefit from a taxane-free second-line chemotherapy regimen, such as FOLFIRI and ramucirumab (FOLFIRI-Ram). Therefore, the RAMIRIS phase III trial evaluates the effects of the regimen of FOLFIRI-Ram in the second-line treatment after a taxane-based chemotherapy in patients with advanced GEA.
FDA Approval Summary: Ramucirumab for Gastric Cancer. [2023]The FDA approved ramucirumab (CYRAMZA; Eli Lilly and Company) for previously treated patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma initially as monotherapy (April 21, 2014) and subsequently as combination therapy with paclitaxel (November 5, 2014). In the monotherapy trial, 355 patients in the indicated population were randomly allocated (2:1) to receive ramucirumab or placebo, 8 mg/kg intravenously every 2 weeks. In the combination trial, 665 patients were randomly allocated (1:1) to receive ramucirumab or placebo, 8 mg/kg intravenously every 2 weeks, in combination with paclitaxel, 80 mg/m(2) on days 1, 8, and 15 of 28-day cycles. Overall survival (OS) was increased in patients who received ramucirumab in both the monotherapy [HR, 0.78; 95% confidence interval (CI), 0.60-0.998; log rank P = 0.047] and combination trials (HR, 0.81; 95% CI, 0.68-0.96; P = 0.017). The most common adverse reactions were hypertension and diarrhea in the monotherapy trial and fatigue, neutropenia, diarrhea, and epistaxis in the combination trial. Because of concerns about the robustness of the monotherapy trial results, FDA approved the original application after receiving the results of the combination trial confirming the OS effect. Based on exploratory exposure-response analyses, there is residual uncertainty regarding the optimal dose of ramucirumab.
Outcomes of Ramucirumab Plus Paclitaxel Among Patients With Previously Treated Metastatic Gastric/Lower Esophageal Cancer: A Real-world Study. [2023]The objective of this study was to review real-world patterns of chemotherapy utilization among patients with metastatic gastric/lower esophageal adenocarcinoma with particular focus on the use of ramucirumab plus paclitaxel in previously treated patients.
Paclitaxel With or Without Cixutumumab as Second-Line Treatment of Metastatic Esophageal or Gastroesophageal Junction Cancer: A Randomized Phase II ECOG-ACRIN Trial. [2023]Patients with advanced esophageal cancer carry poor prognoses; limited data exist to guide second-line therapy in the metastatic setting. Paclitaxel has been used yet is associated with limited efficacy. There is preclinical evidence of synergy between paclitaxel and cixutumumab, a monoclonal antibody targeting insulin-like growth factor-1 receptor. We conducted a randomized phase II trial of paclitaxel (arm A) versus paclitaxel plus cixutumumab (arm B) in the second-line for patients with metastatic esophageal or gastroesophageal junction (GEJ) cancers.
[Phase II study of paclitaxel and cisplatin for advanced squamous-cell carcinoma of esophagus]. [2015]Paclitaxel was used in a phase II trial in combination with cisplatin for esophageal cancer. The anti-tumor response, toxicity and survival of the treated patients were evaluated.
Paclitaxel in the treatment of esophageal cancer. [2015]Since its introduction, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated significant antitumor activity in epidermoid carcinomas and adenocarcinomas originating in the esophagus. Paclitaxel is the most active single agent available to treat metastatic esophageal cancer. Combinations of paclitaxel and cisplatin enhance response rates, but the addition of 5-fluorouracil to this combination only increases toxicity without notably augmenting clinical benefit. Paclitaxel also has been incorporated into numerous preoperative regimens for patients with potentially resectable esophageal cancer. While the optimal use of this agent remains undefined in the postoperative setting, it is clear that paclitaxel will be incorporated into the next generation of preoperative chemotherapy or combined chemotherapy plus radiotherapy regimens for operable esophageal cancer.