Esophageal Squamous Cell Carcinoma (ESCC) Clinical Trial
Official title:
A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents With or Without Pembrolizumab (MK-3475) and/or Chemotherapy in Participants With Advanced Esophageal Cancer naïve to PD-1/PD-L1 Treatment (KEYMAKER-U06): Substudy 06A.
This is a phase I/II multicenter, open-label umbrella platform study that will evaluate the safety and efficacy of investigational agents with pembrolizumab, plus chemotherapy or lenvatinib, for the treatment of participants with advanced esophageal cancer who have failed 1 prior line of therapy and have not been previously exposed to programmed cell death 1 protein (PD-1)/ programmed cell death ligand 1 (PD-L1) based treatment. With protocol amendment 5 (effective: 17-November-2023), enrollment in study arms "Pembrolizumab plus MK-4830 plus Chemotherapy" and "Pembrolizumab plus MK-4830 plus lenvatinib" is discontinued.
| Status | Recruiting |
| Enrollment | 120 |
| Est. completion date | September 21, 2026 |
| Est. primary completion date | November 8, 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | The main inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable ESCC - Has experienced investigator documented radiographic or clinical disease progression on one prior line of standard therapy. - Has an evaluable baseline tumor sample (newly obtained or archival) for analysis - Has adequately controlled blood pressure (BP) with or without antihypertensive medications - Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to =Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have =Grade 2 neuropathy are eligible Exclusion Criteria: - Direct invasion into adjacent organs such as the aorta or trachea - Has experienced weight loss >10% over approximately 2 months prior to first dose of study therapy - Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration - Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication - Known additional malignancy that is progressing or has required active treatment within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that has undergone potentially curative therapy - Known active central nervous system (CNS) metastases and/or carcinomatous meningitis - Active autoimmune disease that has required systemic treatment in past 2 years - History of human immunodeficiency virus (HIV) infection - History of Hepatitis B or known active Hepatitis C virus infection - History of allogenic tissue/solid organ transplant - Clinically significant cardiovascular disease within 12 months from first dose of study intervention - Participants with known gastrointestinal (GI) malabsorption or any other condition that may affect the absorption of lenvatinib - Has risk for significant GI bleeding, such as: - Has had a serious nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to allocation/randomization - Has significant bleeding disorders, vasculitis, or has had a significant bleeding episode from the GI tract within 12 weeks prior to allocation/randomization |
| Country | Name | City | State |
|---|---|---|---|
| Brazil | Liga Norte Riograndense Contra o Câncer ( Site 2303) | Natal | Rio Grande Do Norte |
| Brazil | Hospital Nossa Senhora da Conceição ( Site 2301) | Porto Alegre | Rio Grande Do Sul |
| Brazil | ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 2300) | São Paulo | Sao Paulo |
| Chile | Clínica las Condes ( Site 2403) | Santiago | Region M. De Santiago |
| Chile | FALP-UIDO ( Site 2400) | Santiago | Region M. De Santiago |
| France | Centre Hospitalier Régional Universitaire de Brest - Hôpital Morvan ( Site 1104) | Brest | Finistere |
| France | Hopital Claude Huriez - CHU de Lille ( Site 1100) | Lille | Nord |
| France | Pitie Salpetriere University Hospital ( Site 1102) | Paris | Orne |
| Germany | Charité Campus Virchow-Klinikum-Klinik Hämatologie Onkologie Tumorimmunologie ( Site 2804) | Berlin | |
| Germany | Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 2806) | Dresden | Sachsen |
| Germany | Universitaetsklinikum Duesseldorf ( Site 2802) | Düsseldorf | Nordrhein-Westfalen |
| Germany | Institut für Klinisch Onkologische Forschung-Klink für Onkologie und Hämatologie ( Site 2801) | Frankfurt | Hessen |
| Italy | Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1200) | Milan | Lombardia |
| Italy | Istituto Europeo di Oncologia IRCCS-Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative ( | Milano | |
| Italy | Ospedale San Raffaele-Oncologia Medica ( Site 1206) | Milano | Lombardia |
| Italy | Istituto Oncologico Veneto IRCCS ( Site 1205) | Padova | |
| Japan | National Cancer Center Hospital ( Site 1700) | Chuo-ku | Tokyo |
| Japan | Saitama Prefectural Cancer Center ( Site 1703) | Ina-machi | Saitama |
| Japan | National Cancer Center Hospital East ( Site 1701) | Kashiwa | Chiba |
| Japan | Shizuoka Cancer Center ( Site 1704) | Nagaizumi-cho,Sunto-gun | Shizuoka |
| Japan | Aichi Cancer Center Hospital ( Site 1702) | Nagoya | Aichi |
| Korea, Republic of | Asan Medical Center-Department of Oncology ( Site 1901) | Seoul | |
| Korea, Republic of | Samsung Medical Center-Division of Hematology/Oncology ( Site 1900) | Seoul | |
| Norway | Oslo universitetssykehus, Radiumhospitalet ( Site 2501) | Oslo | |
| Singapore | National University Hospital ( Site 1800) | Singapore | South West |
| Switzerland | Kantonsspital Graubünden-Medizin ( Site 2700) | Chur | Grisons |
| Switzerland | Hôpitaux Universitaires de Genève (HUG) ( Site 2702) | Genève | Geneve |
| Taiwan | Chang Gung Memorial Hospital at Kaohsiung ( Site 2003) | Kaohsiung Niao Sung Dist | Kaohsiung |
| Taiwan | China Medical University Hospital ( Site 2007) | Taichung | |
| Taiwan | Taichung Veterans General Hospital-Radiation Oncology ( Site 2008) | Taichung | |
| Taiwan | National Cheng Kung University Hospital ( Site 2001) | Tainan | |
| Taiwan | National Taiwan University Hospital ( Site 2000) | Taipei | |
| Taiwan | Taipei Veterans General Hospital ( Site 2005) | Taipei | |
| Taiwan | Chang Gung Medical Foundation-Linkou Branch ( Site 2006) | Taoyuan | |
| Thailand | Chulalongkorn University ( Site 2104) | Bangkok | Krung Thep Maha Nakhon |
| Thailand | Faculty of Medicine Siriraj Hospital ( Site 2102) | Bangkok | Krung Thep Maha Nakhon |
| Thailand | Songklanagarind hospital ( Site 2105) | Hatyai | Songkhla |
| Turkey | Adana Medical Park Seyhan Hastanesi-Medikal Onkoloji ( Site 1417) | Adana | |
| Turkey | Ankara City Hospital-Medical Oncology ( Site 1405) | Ankara | |
| Turkey | Hacettepe Universite Hastaneleri-oncology hospital ( Site 1402) | Ankara | |
| Turkey | Memorial Ankara Hastanesi-Medical Oncology ( Site 1408) | Ankara | |
| Turkey | Akdeniz Universitesi Hastanesi-Medical Oncology ( Site 1410) | Antalya | |
| Turkey | Atatürk Üniversitesi-onkoloji ( Site 1416) | Erzurum | |
| Turkey | TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1403) | Istanbul | |
| Turkey | I.E.U. Medical Point Hastanesi-Oncology ( Site 1406) | Izmir, Karsiyaka | Izmir |
| Turkey | Acibadem Altunizade Hospital-Oncology ( Site 1407) | Üsküdar / Istanbul | Istanbul |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC |
Brazil, Chile, France, Germany, Italy, Japan, Korea, Republic of, Norway, Singapore, Switzerland, Taiwan, Thailand, Turkey,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants Experiencing a Dose-limiting Toxicity (DLT) During Safety Lead-in Phase | A DLT is defined as any drug-related adverse event (AE) according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0, observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle. | Up to approximately 3 weeks | |
| Primary | Number of Participants Experiencing an Adverse Event (AE) During Safety Lead-in Phase | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. | Up to approximately 3 Weeks | |
| Primary | Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. | Up to approximately 3 weeks | |
| Primary | Objective Response Rate (ORR) | ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented. | Up to approximately 119 weeks | |
| Secondary | Progression-Free Survival (PFS) | PFS is defined as the time from allocation to the first documented progressive disease (PD) as assessed by RECIST 1.1 or death due to any cause, whichever occurs first. PD is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented. | Up to approximately 216 weeks | |
| Secondary | Duration of Response (DOR) | For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented. | Up to approximately 216 weeks | |
| Secondary | Overall Survival (OS) | OS is defined as the time from the date of allocation to death from any cause. | Up to approximately 216 weeks | |
| Secondary | Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. | Up to approximately 216 weeks | |
| Secondary | Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. | Up to approximately 104 weeks |
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