Clinical trial • Phase I/II • Oncology
LENVATINIB for Advanced esophageal squamous cell carcinoma
Phase I/II trial of LENVATINIB for Advanced esophageal squamous cell carcinoma. open-label, adaptive. 68 participants.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Advanced esophageal squamous cell carcinoma
- Trial Stage
- Phase I/II
- Drug Modality
- Small molecule|Monoclonal antibody|ADC
Key dates
- Initial CTIS Submission Date
- 31-05-2024
- First CTIS Authorization Date
- 24-06-2024
Trial design
open-label, adaptive Phase I/II trial across 8 sites in Norway, Germany, Italy.
- Open Label
- Yes
- Adaptive
- True, Safety Lead-In Phase with monitoring of dose-limiting toxicities (DLTs) to evaluate safety and tolerability before proceeding; umbrella/platform design to evaluate multiple investigational agents and combinations.
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 68
Eligibility
Recruits 68 No vulnerable populations selected; standard informed consent from participants is required. No assent or special consent procedures for minors or other vulnerable groups are mentioned..
- Vulnerable Population
- No vulnerable populations selected; standard informed consent from participants is required. No assent or special consent procedures for minors or other vulnerable groups are mentioned.
Inclusion criteria
- {"criterion_text":"- Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable esophageal squamous cell carcinoma (ESCC).\n- Has experienced investigator documented radiographic or clinical disease progression on one prior line of standard therapy, that includes a platinum agent and previous exposure to an anti-programmed cell death 1 (PD1)/programmed cell death ligand 1 (PD-L1) based immuneoncology (IO) therapy.\n- Has provided an archival or most recent tumor tissue sample obtained as part of clinical practice.\n- 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
- {"criterion_text":"- Direct invasion into adjacent organs such as the aorta or trachea.\n- Clinically significant cardiovascular disease within 12 months from first dose of study intervention.\n- Has risk for significant GI bleeding such as a serious nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to allocation/randomization, significant bleeding disorders, vasculitis, or has had a significant bleeding episode from the GI tract within 12 weeks prior to allocation/randomization.\n- Has experienced weight loss >10% over approximately 2 months prior to first dose of study therapy.\n- Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.\n- Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease.\n- Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.\n- 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.\n- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.\n- Participants with human immunodeficiency virus (HIV) with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease.\n- History of allogenic tissue/solid organ transplant."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Number of Participants Experiencing Dose-limiting Toxicities (DLTs) During Safety Lead-in Phase\n- Number of Participants Who Experienced an Adverse Event (AE) During Safety Lead-in Phase\n- Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase\n- Objective Response Rate (ORR)","definition_or_measurement_approach":"Number of Participants Experiencing DLTs During Safety Lead-in Phase: counted during Safety Lead-in Phase (safety/tolerability assessment).\nNumber of Participants Who Experienced an AE During Safety Lead-in Phase: counted during Safety Lead-in Phase.\nNumber of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase: count of discontinuations due to AEs during Safety Lead-in Phase.\nObjective Response Rate (ORR): assessed by blinded independent central review (BICR) per RECIST 1.1."}
Secondary endpoints
- {"endpoint_text":"- Progression-Free Survival (PFS)\n- Duration of Response (DOR)\n- Overall Survival (OS)\n- Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase\n- Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase","definition_or_measurement_approach":"Progression-Free Survival (PFS): efficacy endpoint, assessed by BICR per RECIST 1.1.\nDuration of Response (DOR): assessed by BICR per RECIST 1.1.\nOverall Survival (OS): time to death from any cause.\nNumber of Participants Experiencing at Least One AE During the Efficacy Phase: count/proportion of participants with ≥1 AE during efficacy phase.\nNumber of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase: count of discontinuations due to AEs during efficacy phase."}
Recruitment
- Planned Sample Size
- 68
- Recruitment Window Months
- 55
- Consent Approach
- Informed consent is required; subject information and informed consent forms (ICFs) are provided, with country-specific ICF documents listed for Norway, Germany and Italy. Optional consent modules are present (e.g., optional pregnant partner data privacy, optional DILI sample). No assent procedures for minors are indicated.
Geography
- Total Number Of Sites
- 8
- Total Number Of Participants
- 10
Norway
- Earliest CTIS Part Ii Submission Date
- 08-04-2024
- Latest Decision Or Authorization Date
- 18-11-2025
- Processing Time Days
- 589
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Oslo University Hospital HF
- Department Name
- Enhet for utprøvende kreftbehandling
- Contact Person Name
- Geir Olav Hjortland
- Contact Person Email
- goo@ous-hf.no
Germany
- Earliest CTIS Part Ii Submission Date
- 08-04-2024
- Latest Decision Or Authorization Date
- 18-11-2025
- Processing Time Days
- 589
- Number Of Sites
- 2
- Number Of Participants
- 5
Sites
- Site Name
- Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
- Department Name
- Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie)
- Contact Person Name
- Gunnar Folprecht
- Contact Person Email
- Gunnar.Folprecht@uniklinikum-dresden.de
- Site Name
- Haematologisch Onkologische Praxis Eppendorf
- Contact Person Name
- Eray Gökkurt
- Contact Person Email
- goekkurt@hope-hamburg.de
Italy
- Earliest CTIS Part Ii Submission Date
- 08-04-2024
- Latest Decision Or Authorization Date
- 17-11-2025
- Processing Time Days
- 588
- Number Of Sites
- 5
- Number Of Participants
- 4
Sites
- Site Name
- Azienda Ospedaliero Universitaria Pisana
- Department Name
- U.O. Oncologia Medica 2
- Contact Person Name
- Lorenzo Fornaro
- Contact Person Email
- l.fornaro@ao-pisa.toscana.it
- Site Name
- Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
- Department Name
- Oncologia Medica
- Contact Person Name
- Alessandro Bittoni
- Contact Person Email
- alessandro.bittoni@irst.emr.it
- Site Name
- Istituto Oncologico Veneto
- Department Name
- UOC oncologia 1
- Contact Person Name
- Sara Lonardi
- Contact Person Email
- sara.lonardi@iov.veneto.it
- Site Name
- Fondazione IRCCS Istituto Nazionale Dei Tumori
- Department Name
- S.S. Oncologia Medica Gastroenterologica
- Contact Person Name
- Filippo Pietrantonio
- Contact Person Email
- filippo.pietrantonio@istitutotumori.mi.it
- Site Name
- Ospedale San Raffaele S.r.l.
- Department Name
- Oncologia Medica
- Contact Person Name
- Silvia Foti
- Contact Person Email
- Foti.silvia@hsr.it
Sponsor
Primary sponsor
- Full Name
- Merck Sharp & Dohme LLC
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Signant Health Management Limited
- Responsibilities
- 7
- Name
- PPD Global Central Labs
- Responsibilities
- 4
- Name
- Almac Clinical Services LLC
- Responsibilities
- 3
- Name
- Icon Clinical Research Limited
- Responsibilities
- 15 (Central imaging)
- Name
- Parexel International Corp.
- Responsibilities
- 15 (EUB services (call center and medical services))
- Name
- Clario
- Responsibilities
- 4
- Name
- Frontage Laboratories Inc.
- Responsibilities
- 4
Third parties
- {"country":"United Kingdom","full_name":"Signant Health Management Limited","duties_or_roles":"7","organisation_type":"Pharmaceutical company"}
- {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"3","organisation_type":"Pharmaceutical company"}
- {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"15 (Central imaging)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"15 (EUB services (call center and medical services))","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Clario","duties_or_roles":"4","organisation_type":"Industry"}
- {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Lenvatinib
- Active Substance
- LENVATINIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Authorisation Status
- Not authorised
- Investigational Product Name
- PACLITAXEL
- Active Substance
- PACLITAXEL
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- INTRAVENOUS
- Authorisation Status
- Not authorised
- Investigational Product Name
- MK-4830
- Active Substance
- MK-4830
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS USE
- Route
- INTRAVENOUS
- Authorisation Status
- Not authorised
- Investigational Product Name
- KEYTRUDA 25 mg/mL concentrate for solution for infusion
- Active Substance
- PEMBROLIZUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS USE
- Route
- INTRAVENOUS
- Authorisation Status
- Authorised (EU/1/15/1024/002)
- Investigational Product Name
- MK-2870 (sacituzumab tirumotecan)
- Active Substance
- SACITUZUMAB TIRUMOTECAN
- Modality
- ADC
- Routes Of Administration
- SOLUTION FOR INJECTION / INTRAVENOUS
- Route
- INTRAVENOUS
- Authorisation Status
- Not authorised
- Investigational Product Name
- IRINOTECAN
- Active Substance
- IRINOTECAN HYDROCHLORIDE
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- INTRAVENOUS
- Authorisation Status
- Not authorised
- Combination Treatment
- Yes
Related trials
Other published trials that may interest you.
- GDC-9545 for Locally advanced or metastatic estrogen receptor-positive breast cancer
- Abemaciclib for Stage IV lung cancer | Breast cancer
- BGB-43395 for Advanced or metastatic solid tumors | Hormone receptor positive HER2 negative breast cancer
- AZD9833 for Estrogen receptor-positive HER2-negative advanced breast cancer
- Pembrolizumab for Classical Hodgkin lymphoma | Melanoma | Solid tumours (MSI-H/dMMR) | Solid tumours (TMB-H)