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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05743036




Registration number
NCT05743036
Ethics application status
Date submitted
26/01/2023
Date registered
24/02/2023

Titles & IDs
Public title
ZN-c3 in Adult Participants with Metastatic Colorectal Cancer
Scientific title
A Phase 1/2, Open-Label, Multi-Center Study of ZN-c3 Administered in Combination with Encorafenib and Cetuximab in Adults with Metastatic Colorectal Cancer
Secondary ID [1] 0 0
Z0011001
Secondary ID [2] 0 0
ZN-c3-016
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic 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 - ZN-c3
Treatment: Drugs - Encorafenib
Treatment: Drugs - Cetuximab

Experimental: Dose Escalation - Participants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab

Experimental: Dose Expansion - Participants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab


Treatment: Drugs: ZN-c3
ZN-c3 tablet by mouth, in combination with encorafenib

Treatment: Drugs: Encorafenib
Encorafenib capsule by mouth, in combination with ZN-c3

Treatment: Drugs: Cetuximab
Infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Escalation Phase - Incidence of Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
From Lead-in Day -1 to Cycle 1 Day 28
Primary outcome [2] 0 0
Dose Expansion Phase - Objective response rate (ORR)
Timepoint [2] 0 0
From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary outcome [1] 0 0
Dose Escalation Phase - Incidence and severity of adverse events (AEs) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0
Timepoint [1] 0 0
From first dose of any study intervention through 28 days after the last dose of any study intervention
Secondary outcome [2] 0 0
Proportion of participants with dose interruptions due to AEs in Dose Escalation Phase
Timepoint [2] 0 0
From first dose of any study intervention through 28 days after the last dose of any study intervention
Secondary outcome [3] 0 0
Proportion of participants with dose modifications due to AEs in Dose Escalation Phase
Timepoint [3] 0 0
From first dose of any study intervention through 28 days after the last dose of any study intervention
Secondary outcome [4] 0 0
Proportion of participants with discontinuations due to AEs in Dose Escalation Phase
Timepoint [4] 0 0
From first dose of any study intervention through 28 days after the last dose of any study intervention
Secondary outcome [5] 0 0
Dose Escalation Phase - Objective response rate (ORR)
Timepoint [5] 0 0
From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary outcome [6] 0 0
Dose Escalation Phase - Duration of Response (DOR)
Timepoint [6] 0 0
From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary outcome [7] 0 0
Dose Escalation Phase - Progression Free Survival (PFS)
Timepoint [7] 0 0
From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary outcome [8] 0 0
Dose Escalation Phase - Disease Control Rate (DCR)
Timepoint [8] 0 0
From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary outcome [9] 0 0
Dose Escalation Phase - Time to Response (TTR)
Timepoint [9] 0 0
From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary outcome [10] 0 0
Dose Escalation - ZN-c3 plasma exposure: AUC
Timepoint [10] 0 0
From lead in day -1 visit through Cycle 1 Day 15
Secondary outcome [11] 0 0
Dose Escalation - ZN-c3 plasma exposure: Cmax
Timepoint [11] 0 0
From lead in day -1 visit through Cycle 1 Day 15
Secondary outcome [12] 0 0
Dose Escalation - ZN-c3 plasma exposure: Tmax
Timepoint [12] 0 0
From lead in day -1 visit through Cycle 1 Day 15
Secondary outcome [13] 0 0
Dose Escalation - Encorafenib plasma exposure: AUC
Timepoint [13] 0 0
From lead in day -1 visit through Cycle 1 Day 15
Secondary outcome [14] 0 0
Dose Escalation - Encorafenib plasma exposure: Cmax
Timepoint [14] 0 0
From lead in day -1 visit through Cycle 1 Day 15
Secondary outcome [15] 0 0
Dose Escalation - Encorafenib plasma exposure: Tmax
Timepoint [15] 0 0
From lead in day -1 visit through Cycle 1 Day 15
Secondary outcome [16] 0 0
Dose Expansion Phase - Duration of Response (DOR)
Timepoint [16] 0 0
From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary outcome [17] 0 0
Dose Expansion Phase - Progression Free Survival (PFS)
Timepoint [17] 0 0
From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary outcome [18] 0 0
Dose Expansion Phase - Disease Control Rate (DCR)
Timepoint [18] 0 0
From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary outcome [19] 0 0
Dose Expansion Phase - Time to Response (TTR)
Timepoint [19] 0 0
From first dose of any study intervention every 8 weeks during treatment, up to 12 months
Secondary outcome [20] 0 0
Dose Expansion Phase - Incidence and severity of adverse events (AEs) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0
Timepoint [20] 0 0
From first dose of any study intervention through 28 days after the last dose of any study intervention
Secondary outcome [21] 0 0
Proportion of participants with dose interruptions due to AEs in Dose Expansion Phase
Timepoint [21] 0 0
From first dose of any study intervention through 28 days after the last dose of any study intervention
Secondary outcome [22] 0 0
Proportion of participants with dose modifications due to AEs in Dose Expansion Phase
Timepoint [22] 0 0
From first dose of any study intervention through 28 days after the last dose of any study intervention
Secondary outcome [23] 0 0
Proportion of participants with discontinuations due to AEs in Dose Expansion Phase
Timepoint [23] 0 0
From first dose of any study intervention through 28 days after the last dose of any study intervention
Secondary outcome [24] 0 0
Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: AUC
Timepoint [24] 0 0
Lead in day 7
Secondary outcome [25] 0 0
Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Cmax
Timepoint [25] 0 0
Lead in day 7
Secondary outcome [26] 0 0
Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Tmax
Timepoint [26] 0 0
Day 7
Secondary outcome [27] 0 0
Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: AUC
Timepoint [27] 0 0
Cycle 1 Day 15
Secondary outcome [28] 0 0
Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Cmax
Timepoint [28] 0 0
Cycle 1 Day 15
Secondary outcome [29] 0 0
Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Tmax
Timepoint [29] 0 0
Cycle 1 Day 15
Secondary outcome [30] 0 0
Dose Expansion - ZN-c3 plasma exposure: AUC
Timepoint [30] 0 0
Cycle 1 Day 15
Secondary outcome [31] 0 0
Dose Expansion - ZN-c3 plasma exposure: Cmax
Timepoint [31] 0 0
Cycle 1 Day 15
Secondary outcome [32] 0 0
Tumor tissue BRAF V600E mutational status
Timepoint [32] 0 0
From lead in day 1 visit through the last dose of any study intervention, up to 12 months

Eligibility
Key inclusion criteria
* Histologically or cytologically confirmed metastatic Stage IV colorectal adenocarcinoma.
* Documented evidence of a BRAF V600E mutation in tumor tissue or blood
* Presence of measurable disease per RECIST version 1.1 guidelines.
* Disease progression after 1 or 2 previous systemic regimens for metastatic disease
* Adequate bone marrow function
* Adequate hepatic and renal function
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Documented clinical disease progression or radiographic disease progression during the screening period
* Leptomeningeal disease.
* Symptomatic brain metastasis.
* Presence of acute or chronic pancreatitis.
* Unable to swallow, retain, and absorb oral medications.
* Clinically significant cardiovascular diseases
* Evidence of active noninfectious pneumonitis.
* Evidence of active and uncontrolled bacterial or viral infection, within 2 weeks prior to start of any of the study interventions
* Participants with known positivity for HIV
* Active hepatitis B or hepatitis C infection
* Concurrent or previous other malignancy within 2 years of study entry
* Has had an allogeneic tissue/solid organ transplant
* Pregnant or females of childbearing potential who have a positive ß-hCG laboratory test result within 14 days prior to enrollment or is breastfeeding

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
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
27/02/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
25/09/2026
Actual
Sample size
Target
82
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
5011 - Woodville South
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Kansas
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
Germany
State/province [4] 0 0
Bayern
Country [5] 0 0
Germany
State/province [5] 0 0
Hessen
Country [6] 0 0
Germany
State/province [6] 0 0
Berlin
Country [7] 0 0
Hungary
State/province [7] 0 0
Budapest
Country [8] 0 0
Hungary
State/province [8] 0 0
Gyöngyös
Country [9] 0 0
Italy
State/province [9] 0 0
Campania
Country [10] 0 0
Italy
State/province [10] 0 0
Foggia
Country [11] 0 0
Italy
State/province [11] 0 0
Veneto
Country [12] 0 0
Italy
State/province [12] 0 0
Milano
Country [13] 0 0
Poland
State/province [13] 0 0
Malopolskie
Country [14] 0 0
Poland
State/province [14] 0 0
Mazowieckie
Country [15] 0 0
Poland
State/province [15] 0 0
Opolskie
Country [16] 0 0
Spain
State/province [16] 0 0
Cataluna
Country [17] 0 0
Spain
State/province [17] 0 0
Cordoba
Country [18] 0 0
Spain
State/province [18] 0 0
Valenciana, Comunitat
Country [19] 0 0
Spain
State/province [19] 0 0
Barcelona
Country [20] 0 0
Spain
State/province [20] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Pfizer
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
K-Group Beta, Inc. a subsidiary of Zentalis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
(212) 433-3791
Fax 0 0
Email 0 0
info@zenopharma.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05743036