Overview
Sponsor-declared trial summary
Phase
Human pharmacology (Phase I) - Other
Status
Suspended
Participants planned
43
Countries
1
Sites
1
Metastatic colorectal cancer
To determine the RP2D of LB−100 combined with azenosertib in metastatic CRC patients.
Key facts
- Sponsor
- Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Decision date (initial)
- 2024-06-28
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy, Pharmacokinetic
To determine the RP2D of LB−100 combined with azenosertib in metastatic CRC patients.
Secondary objectives 2
- To characterise the safety and tolerability of LB−100 and azenosertib, assessed by the incidence and severity of AEs and DLTs, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0)
- To determine the preliminary antitumour activity of the combination LB−100 and azenosertib measured by the disease control rate (DCR), objective response rate (ORR), duration of overall response (DoR), progression free survival (PFS) and overall survival (OS).
Conditions and MedDRA coding
Metastatic colorectal cancer
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | PT | 10052358 | Colorectal cancer metastatic | 100000004864 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Able to understand and voluntarily sign the informed consent (IC) form.
- Patient ≥ 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Histological or cytological confirmation of advanced CRC
- Patient has no curative treatment options in standard of care. This should include at least a fluoropyrimide based regimen, oxaliplatin and/or irinotecan.
- Presence of at least one measurable lesion defined by the Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1)
Exclusion criteria 9
- Unable to follow study procedures
- Patients using prohibited medication
- Any unresolved grade ≥ 2 toxicities related to prior treatments (excluding alopecia) according to CTCAE version 5.0
- Participants with a clinically significant gastrointestinal disorder that in the opinion of the treating investigator could impact the absorption of azenosertib
- Symptomatic or untreated leptomeningeal disease
- Symptomatic or actively progressing central nervous system metastases
- History of another malignancy, exclusions are listed in the protocol
- Patient with cardiac comorbidities as listed in the protocol
- Pregnant or breast–feeding (lactating) women
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The endpoint will be the incidence of DLTs.
Secondary endpoints 2
- To characterise the safety and tolerability of LB−100 and azenosertib. The endpoint is the incidence and severity of AEs and DLTs.
- To determine the efficacy of the combination LB−100 and azenosertib. The endpoints are the DCR, ORR, PFS, OS and DoR.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
3-4-METHYLPIPERAZINE-1-CARBONYL-7-OXABICLO221HEPTANE-2-CARBOXYLIC Acid
PRD11036856 · Product
- Active substance
- 3-4-METHYLPIPERAZINE-1-CARBONYL-7-OXABICLO221HEPTANE-2-CARBOXYLIC Acid
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 3.10 mg/m2 milligram(s)/square meter
- Max total dose
- 217 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 104 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS STICHTING
- Paediatric formulation
- No
- Orphan designation
- No
azenosertib, also known as ZN-c3
PRD9495924 · Product
- Active substance
- Azenosertib
- Substance synonyms
- KP-2638, ZN-c3, (R)-2-allyl-1-(7-ethyl-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)-6-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 210000 mg milligram(s)
- Max treatment duration
- 104 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- K-GROUP BETA, INC.
- Paediatric formulation
- No
- Orphan designation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
- Sponsor organisation
- Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
- Address
- Plesmanlaan 121
- City
- Amsterdam
- Postcode
- 1066 CX
- Country
- Netherlands
Scientific contact point
- Organisation
- Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
- Contact name
- Clinical Research Unit
Public contact point
- Organisation
- Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
- Contact name
- Clinical Research Unit
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Suspended | 43 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
Oncology, Plesmanlaan 121, 1066 CX, Amsterdam
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Corrective measures 1 · Art. 77 CTR
Corrective measure CM-NL-0001
- Member state
- Netherlands
- Publication date
- 2024-11-08
- Type
- 5
- Reason
- 6
- Immediate action required
- Yes
- Justification
- Given the suspected immunological toxicity in the two patients in the CoLBat trial, more insight is to be provided into the working mechanism and pharmacology of LB-100 and its active metabolites.
Please provide:
a) extensive drug-drug interaction studies between LB-100 and its active metabolites and both atezolizumab and azenosertib
b) perform studies into potential other drug-drug interactions for LB-100 and its metabolites by investigating their impact on major metabolic pathways
c) provide additional toxicity data on the synergistic effect of LB-100 and both atezolizumab and azenosertib
d) provide a proposal on how to mitigate immunological toxicity in future patients in both the CoLBat and the COLLEE trials.
e) A current overview from the manufacturer of all SUSARs involving LB-100 that have occurred worldwide must also be submitted.
Please also provide an update of the IB of LB-100 as the current version is 1 year old. Please put extra emphasis on toxicity data.
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 12 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Study Protocol_2024-511227-33-00_Geredigeerd | 1.4 |
| Protocol (for publication) | D1_Study Protocol_2024-511227-33-00_TC | 1.4 |
| Recruitment arrangements (for publication) | K1_Recruitment_procedure | 1.0 |
| Subject information and informed consent form (for publication) | L1_Proefpersoneninformatie Deel 1_Geredigeerd | 2.0 |
| Subject information and informed consent form (for publication) | L1_Proefpersoneninformatie Deel 1_TC | 2.0 |
| Subject information and informed consent form (for publication) | L1_Proefpersoneninformatie Deel 2_Geredigeerd | 2.0 |
| Subject information and informed consent form (for publication) | L1_Proefpersoneninformatie Deel 2_TC | 2.0 |
| Subject information and informed consent form (for publication) | L1_Proefpersoneninformatie Zwangere Partner vd proefpersoon_Geredigeerd | 01 |
| Subject information and informed consent form (for publication) | L1_Proefpersoneninformatie Zwangere proefpersoon_Geredigeerd | 1.1 |
| Subject information and informed consent form (for publication) | L1_Proefpersoneninformatie Zwangere proefpersoon_TC | 1.1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_ENG_2024-511227-33-00 | 2.0 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_NL_2024-511227-33-00 | 2.0 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-03-05 | Netherlands | Acceptable with conditions 2024-06-24
|
2024-06-28 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-08-16 | Netherlands | Acceptable with conditions 2024-11-04
|
2024-11-08 |