Sacituzumab Tirumotecan for Endometrial Cancer
(TroFuse-005 Trial)
Recruiting in Palo Alto (17 mi)
+246 other locations
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Merck Sharp & Dohme LLC
Must not be taking: TROP2 ADCs, Topoisomerase I ADCs
Disqualifiers: Neuroendocrine tumors, Severe eye disease, Inflammatory bowel disease, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?Researchers are looking for new ways to treat people with endometrial cancer (EC) who have previously received treatment with platinum based therapy (a type of chemotherapy) and immunotherapy. Immunotherapy is a treatment that helps the immune system fight cancer. This clinical study will compare MK-2870 sacituzumab tirumotecan to chemotherapy. The goal of the study is to learn if people who receive MK-2870 sacituzumab tirumotecan live longer overall and without the cancer getting worse compared to people who receive chemotherapy.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it does list certain treatments that participants should not have received before joining the trial, like specific chemotherapy drugs and targeted therapies.
What evidence supports the effectiveness of the drug Sacituzumab Tirumotecan for endometrial cancer?
Research shows that combinations of drugs like doxorubicin, paclitaxel, and cisplatin have been effective in treating advanced or recurrent endometrial cancer, with response rates improving when paclitaxel is added. While Sacituzumab Tirumotecan is not directly mentioned, the effectiveness of similar drug combinations suggests potential benefits.
12345What safety data exists for Sacituzumab Tirumotecan and related treatments?
Doxorubicin and paclitaxel, which are related to Sacituzumab Tirumotecan, have been associated with heart-related side effects, such as changes in heart rhythm and cardiomyopathy (heart muscle disease). Liposomal doxorubicin may have advantages over regular doxorubicin due to its potential for reduced heart toxicity. Paclitaxel can also cause side effects like nerve damage, allergic reactions, and changes in blood cell counts.
56789How is the drug Sacituzumab Tirumotecan different from other treatments for endometrial cancer?
Sacituzumab Tirumotecan is unique because it combines an antibody-drug conjugate (a targeted therapy that links a drug to an antibody to deliver it directly to cancer cells) with chemotherapy agents like Doxorubicin and Paclitaxel, potentially offering a more targeted approach compared to traditional chemotherapy regimens.
1251011Eligibility Criteria
This trial is for individuals with endometrial cancer who have already undergone treatment with platinum-based chemotherapy and immunotherapy but need additional treatment. Participants should meet specific health criteria as determined by the study's guidelines.Inclusion Criteria
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either sacituzumab tirumotecan or chemotherapy. Sacituzumab tirumotecan is administered as 4 mg/kg IV infusion on Day 1 of each 14-day cycle. Chemotherapy options include doxorubicin 60 mg/m^2 IV on Day 1 of each 21-day cycle or paclitaxel 80 mg/m^2 IV on Days 1, 8, and 15 of each 28-day cycle.
Up to approximately 4 years
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Open-label extension (optional)
Participants may opt into continuation of treatment long-term
Long-term
Participant Groups
The study aims to compare a new medication, MK-2870, against treatments that doctors usually choose (TPC) in terms of how long patients live without their cancer getting worse and overall survival rates.
2Treatment groups
Experimental Treatment
Active Control
Group I: Sacituzumab tirumotecanExperimental Treatment1 Intervention
Participants will receive 4 mg/kg of sacituzumab tirumotecan via intravenous (IV) infusion on Day 1 of each 14-day cycle. Additionally, participants receive diphenhydramine (or equivalent), a Histamine (H2 antagonist) of investigator's choice, acetaminophen (or equivalent), and dexamethasone (or equivalent) per each drug's product label prior to the first 4 infusions of sacituzumab tirumotecan. At subsequent infusions, the H2 antagonist and dexamethasone are optional, at the discretion of the investigator.
Group II: ChemotherapyActive Control2 Interventions
Participants will receive 60 mg/m\^2 of doxorubicin by IV infusion on Day 1 of each 21-day cycle; or 80 mg/m\^2 of paclitaxel by IV infusion on Days 1, 8, and 15 of each 28-day cycle.
Doxorubicin is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Adriamycin for:
- Breast cancer
- Ovarian cancer
- Bladder cancer
- Lymphomas
- Leukemias
- Multiple myeloma
- Kaposi's sarcoma
- Soft tissue sarcomas
🇪🇺 Approved in European Union as Doxorubicin for:
- Breast cancer
- Ovarian cancer
- Bladder cancer
- Lymphomas
- Leukemias
- Multiple myeloma
- Kaposi's sarcoma
- Soft tissue sarcomas
🇨🇦 Approved in Canada as Doxorubicin for:
- Breast cancer
- Ovarian cancer
- Bladder cancer
- Lymphomas
- Leukemias
- Multiple myeloma
- Kaposi's sarcoma
- Soft tissue sarcomas
🇯🇵 Approved in Japan as Doxorubicin for:
- Breast cancer
- Ovarian cancer
- Bladder cancer
- Lymphomas
- Leukemias
- Multiple myeloma
- Kaposi's sarcoma
- Soft tissue sarcomas
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
McGill University Health Centre ( Site 1404)Montréal, Canada
Houston Methodist Hospital-Obstetrics and Gynecology ( Site 4130)Houston, TX
Yale-New Haven Hospital-Smilow Cancer Hospital at Yale-New Haven ( Site 4114)New Haven, CT
NorthShore University HealthSystem - Evanston Hospital ( Site 4110)Evanston, IL
More Trial Locations
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Who Is Running the Clinical Trial?
Merck Sharp & Dohme LLCLead Sponsor
European Network for Gynaecological Oncological Trial groups(ENGOT)Collaborator
GOG FoundationCollaborator
References
Chemotherapy in endometrial cancer. [2007]Endometrial cancer is a highly curable malignancy when it presents as uterine-confined disease, but the prognosis for metastatic or recurrent endometrial cancer is poor. The median survival of women enrolled in trials for recurrent or metastatic endometrial cancer is only approximately 12 months. Hormonal therapy, most commonly with progestins, benefits a small group of patients. Cytotoxic chemotherapy is indicated as frontline treatment for the majority of women with metastatic or recurrent disease. Anthracyclines, platinum compounds, and taxanes consistently achieve response rates greater than 20% in single-agent trials of chemotherapy-naive patients. Combination chemotherapy typically produces higher response rates, although combination regimens have not always improved survival historically. Doxorubicin plus cisplatin has been accepted as the Gynecologic Oncology Group (GOG) standard regimen based on phase III data. Recently, a COG randomized trial compared doxorubicin plus cisplatin to the triplet of doxorubicin, cisplatin, and paclitaxel, and it was found that the addition of paclitaxel significantly improved response rate, progression-free survival, and overall survival. Moreover, chemotherapy has been reported to improve survival when
Paclitaxel, epirubicin, and carboplatin in advanced or recurrent endometrial carcinoma: a Hellenic Co-operative Oncology Group (HeCOG) study. [2015]Taxanes, anthracyclines, and platinum compounds represent the chemotherapeutic agents with the greatest activity in metastatic endometrial carcinoma. We administered the combination of paclitaxel, epirubicin and carboplatin to patients with metastatic or recurrent carcinoma of the endometrium to evaluate its activity and to define its toxicity.
[Chemotherapy of endometrial cancer revisited]. [2017]The current status and future directions of chemotherapy in the management of endometrial cancer are reviewed. For patients with advanced or recurrent endometrial carcinoma the most active single drugs are doxorubicin, epirubicin, cisplatin, carboplatin, paclitaxel, ifosfamide, 5-fluorouracil and vincristine with response rates ranging from 18 to 36%. Data at the present time support the conclusion that if chemotherapy is indicated a combination of doxorubicin + cisplatin is the standard chemotherapy for patients with advanced or recurrent endometrial carcinoma and yields a response rate of 47-60%. A first trial using a combination of these drugs with paclitaxel promises an increase in response rate to 73%, but data regarding prolongation of survival are not yet available. Up to now the benefit of neither chemotherapy nor endocrine therapy could be established in the adjuvant setting.
Phase I trial of paclitaxel, doxorubicin, and carboplatin (TAC) for the treatment of endometrial cancer. [2018]Doxorubicin, platinum compounds, and taxanes represent the chemotherapeutic agents with the greatest activity in endometrial cancer. We conducted an optimal-dose determination of combination chemotherapy consisting of paclitaxel (TXL), doxorubicin, and carboplatin (CBDCA) (TAC) in patients with endometrial cancer. Patients with epithelial endometrial cancer requiring adjuvant therapy were enrolled between June 2003 and March 2005. No patients had received prior radiotherapy, and only two patients had previously undergone chemotherapy. Doxorubicin was infused on day 1, and TXL followed by CBDCA was administered on day 2. The starting dose was doxorubicin 35 mg/m(2), TXL 120 mg/m(2), and CBDCA area under the curve (AUC). The dose of each agent was gradually escalated. Patients were scheduled to receive at least four cycles of therapy. If patients experienced grade 4 neutropenia or neutropenic fever with grade 3 neutropenia, they were permitted to be administered granulocyte colony-stimulating factor after the second course. Twenty-seven patients were enrolled. Although four patients out of 27 experienced dose-limiting toxicities, a maximum tolerated dose was not established at the final dose level. Five patients (three for recurrent and two for advanced) had measurable lesions. There were four responders (three for partial response and one for complete response) in our series. The recommended dose of TAC therapy for endometrial cancer was doxorubicin 45 mg/m(2) for day 1, TXL 150 mg/m(2) and CBDCA AUC 5 for day 2.
Phase II trial of liposomal doxorubicin at 40 mg/m(2) every 4 weeks in endometrial carcinoma: a Gynecologic Oncology Group Study. [2013]In patients with disseminated endometrial carcinoma, liposomal doxorubicin has possible advantages over doxorubicin which has proven single agent activity but well known cardiac toxicity. Before replacing doxorubicin in clinical trials, the Gynecologic Oncology Group (GOG) decided to conduct a phase II clinical trial of liposomal doxorubicin (Ortho Biotech Products L. P., Raritan, NJ) in first-line therapy of patients with disseminated endometrial carcinoma.
[Cardiac tolerance of the combination paclitaxel-anthracyclines in the context of the management of cancer of the breast]. [2015]Within the past decades there has been major interest in associating the paclitaxel into the management of breast cancer patients with a strong improvement of clinical results. Moreover, doxorubicin is historically one of the major chemotherapeutic agents in breast cancer treatment. So, investigations of the combination of the paclitaxel with doxorubicin have logically taken place in the strategy of breast cancer management. Also, this association became a standard of care neoadjuvantly in locally advanced breast cancer. The aim of this review of literature consists to make a special focus on cardiac toxicity occurring after doxorubicin and paclitaxel association and to give adequate directions for the next future in this promising combination.
Cardioprotection by dexrazoxane in rats treated with doxorubicin and paclitaxel. [2015]Results of several clinical studies suggest that the combination of doxorubicin (DOX) and paclitaxel (PTX) is highly active against solid tumors. Both drugs are known to cause adverse cardiac effects, cardiomyopathy in the case of DOX and acute changes in cardiac rhythm in the case of PTX. It has been suggested that the addition of dexrazoxane (DZR) to this regimen may reduce the risk of cardiotoxicity. A model of chronic cardiomyopathy in the rat was used to determine whether DZR was tolerated and cardioprotective in a DOX + PTX combination.
Paclitaxel-based combination chemotherapy for breast cancer. [2015]Clinical trials to develop paclitaxel (Taxol)-containing combinations started in 1992 with several approaches to combine doxorubicin and paclitaxel. Schedule-dependent toxicity limited doses in the initial trials, although antitumor activity was high. More recently, a well-tolerated, highly effective doxorubicin/paclitaxel regimen was developed with the use of bolus anthracycline administration and a 3-hour infusion of paclitaxel. Combinations of paclitaxel with cisplatin have provided mixed results. Paclitaxel combined with fluorouracil (5-FU) and folinic acid proved effective in patients with extensive prior chemotherapy; the addition of mitoxantrone (Novantrone) to this combination was feasible, well tolerated, and possibly enhanced the efficacy of paclitaxel and 5-FU. Combinations of paclitaxel with cyclophosphamide (Cytoxan, Neosar), vinorelbine (Navelbine), edatrexate, and radiation continue in clinical development.
Paclitaxel (taxol). [2019]Paclitaxel is a novel antineoplastic that effects cytotoxicity by promoting intracellular tubulin polymerization and stabilizes abnormal microtubule structures against depolymerization. Although its clinical development had been hampered by misconceptions about its pharmacology, its scarcity, difficulties extracting it from its natural source, formulation problems, and frequent severe hypersensitivity reactions, paclitaxel recently was approved for treatment-refractory ovarian cancer. Two major adverse effects are dosage- and schedule-related myelosuppression and mucositis. Neurotoxicity is directly related to both the individual and cumulative doses. Other relevant toxicities are hypersensitivity reactions, effects on cardiac rate and rhythm, arthralgias and myalgias, generalized hair loss, and mild nausea and emesis. Continuing clinical studies will evaluate paclitaxel as initial therapy for ovarian cancer and its utility in other malignancies. In addition, major efforts are under way to develop alternative sources to increase the availability of taxene analogs and reduce our dependence on yew species.
A multicentre phase II study of carboplatin plus pegylated liposomal doxorubicin as first-line chemotherapy for patients with advanced or recurrent endometrial carcinoma: the END-1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) group. [2018]Anthracyclines and platinum derivates are active drugs for advanced endometrial carcinoma (AEC), but new schedules with higher efficacy and better tolerability are needed. A phase II study was conducted to describe activity and tolerability of carboplatin (C)+pegylated liposomal doxorubicin (PLD) in patients with AEC. Patients with chemonaive AEC, PS
Dose dense carboplatin paclitaxel improves progression free survival in patients with endometrial cancer. [2022]Pilot study to assess the value of weekly paclitaxel plus carboplatin every 3weeks (dose dense regimen, DD) compared to the standard 3-weekly protocol in the adjuvant setting for endometrial cancer.