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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04744831




Registration number
NCT04744831
Ethics application status
Date submitted
19/01/2021
Date registered
9/02/2021

Titles & IDs
Public title
Trastuzumab Deruxtecan in Participants With HER2-overexpressing Advanced or Metastatic Colorectal Cancer
Scientific title
A Phase 2, Multicenter, Randomized, Study of Trastuzumab Deruxtecan in Participants With HER2-overexpressing Locally Advanced, Unresectable or Metastatic Colorectal Cancer (DESTINY-CRC02)
Secondary ID [1] 0 0
2020-004782-39
Secondary ID [2] 0 0
DS8201-A-U207
Universal Trial Number (UTN)
Trial acronym
DESTINY-CRC02
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - DS-8201a 5.4 mg/kg Q3W
Treatment: Drugs - DS-8201a 6.4 mg/kg Q3W

Experimental: T-DXd 5.4 mg/kg Q3W - Participants will be randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).

Experimental: T-DXd 6.4 mg/kg Q3W - Participants will be randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).


Treatment: Drugs: DS-8201a 5.4 mg/kg Q3W
DS-8201a for injection will be administered intravenously (IV) at a dose of 5.4 mg/kg every 3 weeks (Q3W)

Treatment: Drugs: DS-8201a 6.4 mg/kg Q3W
DS-8201a for injection will be administered intravenously (IV) at a dose of 6.4 mg/kg every 3 weeks (Q3W)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review Following IV Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2-overexpressing Metastatic Colorectal Cancer
Timepoint [1] 0 0
6 months post-dose administration to data cut off, up to 20 months
Secondary outcome [1] 0 0
Confirmed Objective Response Rate by Investigator Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer
Timepoint [1] 0 0
6 months post-dose administration to data cut off, up to 40 months
Secondary outcome [2] 0 0
Duration of Response Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer
Timepoint [2] 0 0
6 months post-dose administration to data cut off, up to 40 months
Secondary outcome [3] 0 0
Disease Control Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer
Timepoint [3] 0 0
6 months post-dose administration to data cut off, up to 40 months
Secondary outcome [4] 0 0
Clinical Benefit Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer
Timepoint [4] 0 0
6 months post-dose administration to data cut off, up to 40 months
Secondary outcome [5] 0 0
Progression Free Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer
Timepoint [5] 0 0
6 months post-dose administration to data cut off, up to 40 months
Secondary outcome [6] 0 0
Overall Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer
Timepoint [6] 0 0
6 months post-dose administration to data cut off, up to 40 months
Secondary outcome [7] 0 0
Percentage of Participants Reporting Treatment-emergent Adverse Events Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer
Timepoint [7] 0 0
Baseline up to 40 months
Secondary outcome [8] 0 0
Change From Baseline in Patient-Reported Outcomes (PROs) in European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30)
Timepoint [8] 0 0
Baseline up to 40 months
Secondary outcome [9] 0 0
Change From Baseline in Patient-Reported Outcomes (PROs) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Colorectal Cancer 29 (QLQ-CR29)
Timepoint [9] 0 0
Baseline up to 40 months
Secondary outcome [10] 0 0
Patient-Reported Outcomes (PROs) in the EuroQol Questionnaire (EQ) of 5 Dimensions (5D) on a Standardized 5- Level (5L) Descriptive Health Status Scale (EQ-5D-5L)
Timepoint [10] 0 0
Baseline up to 40 months
Secondary outcome [11] 0 0
Patient-Reported Outcomes (PROs) in Patient's Global Impression of Treatment Tolerability (PGI-TT)
Timepoint [11] 0 0
Baseline up to 40 months
Secondary outcome [12] 0 0
Patient-Reported Outcomes (PROs) in Patient Global Impression of Symptom Severity (PGIS)
Timepoint [12] 0 0
Baseline up to 40 months
Secondary outcome [13] 0 0
Patient-Reported Outcomes (PROs) in Patient Global Impression of Change (PGIC) Scores
Timepoint [13] 0 0
Baseline up to 40 months
Secondary outcome [14] 0 0
Inpatient Healthcare Resource Utilization
Timepoint [14] 0 0
Baseline up to 40 months
Secondary outcome [15] 0 0
Serum Concentration of T-DXd
Timepoint [15] 0 0
Baseline up to 40 months
Secondary outcome [16] 0 0
Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody
Timepoint [16] 0 0
Baseline up to 40 months
Secondary outcome [17] 0 0
Serum Concentration of Active Metabolite MAAA-1181a
Timepoint [17] 0 0
Baseline up to 40 months
Secondary outcome [18] 0 0
Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) in Participants Who Were Administered T-DXd
Timepoint [18] 0 0
Baseline up to 40 months

Eligibility
Key inclusion criteria
KEY

Participants must meet all of the following criteria to be eligible for randomization/registration into the study:

1. Adults aged =20 years in Japan, Taiwan, and Korea, or those aged =18 years in other countries, at the time the Informed Consent Forms (ICFs) are signed.
2. Pathologically-documented, unresectable, recurrent, or metastatic colorectal adenocarcinoma. Participants must have v-raf murine sarcoma viral oncogene homologue B1 (BRAF) wild-type cancer and rat sarcoma viral oncogenes homologue (RAS) status identified in primary or metastatic site.
3. The following therapies should be included in prior lines of therapy:

1. Fluoropyrimidine, oxaliplatin, and irinotecan, unless contraindicated
2. Anti-epidermal growth factor receptor (EGFR) treatment, if RAS wild-type and if clinically indicated
3. Anti-vascular endothelial growth factor (VEGF) treatment, if clinically indicated
4. Anti-programmed death ligand 1 (PD-(L)-1) therapy, if the tumor is microsatellite instability (MSI)-high/deficient mismatch repair (dMMR), or tumor mutational burden (TMB)-high, if clinically indicated
4. Confirmed human epidermal growth factor 2 (HER2)-overexpressing status assessed by central laboratory and defined as immunohistochemistry (IHC) 3+ or IHC 2+/ in situ hybridization (ISH) +.
5. Presence of at least one measurable lesion assessed by the Investigator per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
7. Has left ventricular ejection fraction (LVEF) =50% within 28 days before randomization/registration.

KEY
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants who meet any of the following criteria will be disqualified from entering the study:

1. Medical history of myocardial infarction (MI) within 6 months before randomization/registration, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Participants with troponin levels above the upper limit of normal (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.
2. Has a corrected QT interval corrected with Fridericia's formula (QTcF) prolongation to >470 msec (female participants) or >450 msec (male participants) based on the average of the Screening triplicate 12-lead electrocardiograms (ECGs).
3. 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.
4. Lung-specific intercurrent clinically 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.).
5. Any 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.
6. Prior pneumonectomy.
7. Has 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. Participants with clinically inactive brain metastases may be included in the study. Participants 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.
8. Participants with leptomeningeal carcinomatosis.
9. Has known human immunodeficiency virus (HIV) infection.
10. Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days before study randomization/registration. Participants 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 only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
11. Previous treatment with a DXd-containing antibody-drug conjugate (ADC).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2024
Actual
Sample size
Target
Accrual to date
Final
122
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Flinders Medical Centre (FMC) - Bedford Park
Recruitment hospital [2] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [3] 0 0
Royal Brisbane & Women's Hospital - Brisbane
Recruitment hospital [4] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [5] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
- Bedford Park
Recruitment postcode(s) [2] 0 0
- Blacktown
Recruitment postcode(s) [3] 0 0
- Brisbane
Recruitment postcode(s) [4] 0 0
- Clayton
Recruitment postcode(s) [5] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Kentucky
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
United States of America
State/province [3] 0 0
Tennessee
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Belgium
State/province [5] 0 0
Bruxelles
Country [6] 0 0
Belgium
State/province [6] 0 0
Edegem
Country [7] 0 0
Belgium
State/province [7] 0 0
Gent
Country [8] 0 0
France
State/province [8] 0 0
Lyon Cedex 03
Country [9] 0 0
France
State/province [9] 0 0
MONTPELLIER Cedex 5
Country [10] 0 0
France
State/province [10] 0 0
Nantes
Country [11] 0 0
France
State/province [11] 0 0
Paris
Country [12] 0 0
France
State/province [12] 0 0
Toulouse
Country [13] 0 0
Italy
State/province [13] 0 0
Milano
Country [14] 0 0
Italy
State/province [14] 0 0
Padova
Country [15] 0 0
Italy
State/province [15] 0 0
Vicenza
Country [16] 0 0
Japan
State/province [16] 0 0
Aichi
Country [17] 0 0
Japan
State/province [17] 0 0
Chiba
Country [18] 0 0
Japan
State/province [18] 0 0
Ehime
Country [19] 0 0
Japan
State/province [19] 0 0
Fukuoka
Country [20] 0 0
Japan
State/province [20] 0 0
Hokkaido
Country [21] 0 0
Japan
State/province [21] 0 0
Kanagawa
Country [22] 0 0
Japan
State/province [22] 0 0
Osaka
Country [23] 0 0
Japan
State/province [23] 0 0
Tokyo
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Goyang-si
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Gyeonggi-do
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Seoul
Country [27] 0 0
Spain
State/province [27] 0 0
Barcelona
Country [28] 0 0
Spain
State/province [28] 0 0
Madrid
Country [29] 0 0
Spain
State/province [29] 0 0
Pamplona
Country [30] 0 0
Taiwan
State/province [30] 0 0
Taichung
Country [31] 0 0
Taiwan
State/province [31] 0 0
Tainan
Country [32] 0 0
Taiwan
State/province [32] 0 0
Taipei
Country [33] 0 0
Taiwan
State/province [33] 0 0
Taoyuan
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Daiichi Sankyo
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
AstraZeneca
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Global Clinical Leader
Address 0 0
Daiichi Sankyo
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https:// vivli.org/ourmember/daiichi-sankyo/

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Available to whom?
Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://vivli.org/ourmember/daiichi-sankyo/


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04744831