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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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
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
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.