Trastuzumab deruxtecan for subjects with HER2-overexpressing advanced or metastatic CRC
- Conditions
- HER2-overexpressing Locally Advanced, Unresectable or Metastatic Colorectal CancerMedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004782-39-IT
- Lead Sponsor
- DAIICHI SANKYO INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 120
- Sign and date the Tissue Pre-Screening and Main ICFs, prior to the start of any respective study-specific qualification procedures.
- Adults aged =20 years in Japan, Taiwan, and Korea, or those aged =18 years in other countries, at the time the ICFs are signed. (Please follow local regulatory requirements if the legal age of consent for study participation is >18 years).
- Pathologically-documented, unresectable, recurrent, or metastatic colorectal adenocarcinoma. Subject must have BRAF wild-type cancer and RAS status identified in primary or metastatic site, tested by a Clinical Laboratory Improvement Act (CLIA), ISO15189, or equivalent-certified laboratory.
- The following therapies should be included in prior lines of therapy:
o Fluoropyrimidine, oxaliplatin, and irinotecan, unless contraindicated
o Anti-epidermal growth factor receptor (EGFR) treatment, if RAS wild-type and if clinically indicated
o Anti-vascular endothelial growth factor (VEGF) treatment, if clinically indicated
o Anti-programmed death-ligand 1 (PD-[L]-1) therapy, if tumor is microsatellite instable (MSI)-high/deficient mismatch repair (dMMR), or tumor mutational burden (TMB)-high, if clinically indicated
¿¿Is willing and able to provide an adequate tumor sample for tissue pre-screening to confirm HER2 status by central laboratory (most recent tumor tissue preferred).
- Confirmed HER2-overexpressing status assessed by central laboratory and defined as IHC 3+ or IHC 2+/ISH+.
- Presence of at least one measurable lesion assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Lesions situated in a previously-irradiated area are considered measurable if progression has been demonstrated in such lesions after the end of radiotherapy.
- ECOG PS of 0 or 1.
- Has left ventricular ejection fraction (LVEF) =50% within 28 days before randomization/registration.
- Has adequate organ function within 14 days before randomization/registration,
- Has adequate treatment washout period before randomization/registration
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75
Medical history of myocardial infarction (MI) within 6 mths before randomization/registration, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Subjects with troponin levels above ULN at Screening (as defined by the manufacturer), and without any MI-related symptoms, should have a cardiologic consultation before randomization/registration to rule out MI
Has a corrected QT interval (QTcF) prolongation to >470 msec (female subjects) or >450 msec (male subjects) based on the average of the Screening triplicate 12-lead ECGs
Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
Lung-specific intercurrent clinic significant illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the randomization/registration, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc.)
autoimmune, connective tissue, or inflammatory disorders (eg, rheumatoid arthritis, Sjögren syndrome, sarcoidosis, etc.) where there is documented, or a suspicion of, pulmonary involvement at the time of Screening. Full details of the disorder should be recorded in the eCRF for subjects who are included in the study
Prior pneumonectomy
Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and randomization/registration
Subjects with leptomeningeal carcinomatosis
Has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated
Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
Has a history of severe hypersensitivity reactions to other monoclonal antibodies
Has an uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals
Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions that may in the opinion of the Investigator, interfere with the subject’s partic. in the clinical study or evaluation of the clinical study results
Has known human immunodeficiency virus (HIV) infection. Unless required by local regulations or institutional review board IRB/EC, an HIV antigen/antibody test is not required prior to randomization/enrollment
Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days before study randomization/registration. Subjects with past or resolved hepatitis B virus (HBV) infection are eligible if hepatitis B surface antigen (HBsAg) negative (-) and antibody to hepatitis B core antigen (anti-HBc) positive (+). Patients positive for hepatitis C virus (HCV) antibody are eligible on
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method