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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04200404




Registration number
NCT04200404
Ethics application status
Date submitted
13/12/2019
Date registered
16/12/2019
Date last updated
6/05/2022

Titles & IDs
Public title
A Study of CS1001 in Combination With Regorafenib in Patients With Advanced or Refractory Solid Tumors
Scientific title
A Phase Ib/II, Multicenter Open-label Study of CS1001 in Combination With Regorafenib in Patients With Advanced or Refractory Solid Tumors
Secondary ID [1] 0 0
CS1001/Regorafenib-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Refractory Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CS1001
Treatment: Drugs - Regorafenib

Experimental: Phase Ib arm - arms 1. Phase Ib: advanced or refractory solid tumors;

Experimental: Phase II arm - arms 2.Phase II: subjects with tumor of specific types


Treatment: Drugs: CS1001
One course will last 28 days. CS1001 will be intravenously administered every 4 weeks (Q4W).

Treatment: Drugs: Regorafenib
One course will last 28 days. Administration will be orally (p.o.) taken at different dose schemes.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase Ib (Safety Evaluation): Number of participants with adverse events
Timepoint [1] 0 0
Baseline up to 90 days post last dose, up to 2 years
Primary outcome [2] 0 0
Phase Ib (Safety Evaluation): Dose Limiting Toxicity (DLT)
Timepoint [2] 0 0
Baseline up to 90 days post last dose, up to 2 years
Primary outcome [3] 0 0
Phase II (Efficacy Expansion): Objective response rate (ORR)
Timepoint [3] 0 0
Up to 2 years
Secondary outcome [1] 0 0
Phase Ib (Safety Evaluation): Objective response rate (ORR)
Timepoint [1] 0 0
Up to 2 years
Secondary outcome [2] 0 0
Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Disease control rate (DCR)
Timepoint [2] 0 0
Up to 2 years
Secondary outcome [3] 0 0
Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Progression Free Survival (PFS)
Timepoint [3] 0 0
Up to 2 years
Secondary outcome [4] 0 0
Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Duration of Response (DoR)
Timepoint [4] 0 0
Up to 2 years
Secondary outcome [5] 0 0
Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Overall Survival (OS)
Timepoint [5] 0 0
Up to 2 years
Secondary outcome [6] 0 0
Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Occurrence of anti-CS1001 antibody
Timepoint [6] 0 0
From first dose to 30 days after last dose, up to 2 years
Secondary outcome [7] 0 0
Phase II (Efficacy Expansion): : Number of participants with adverse events
Timepoint [7] 0 0
Baseline up to 90 days post last dose, up to 2 years
Secondary outcome [8] 0 0
Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Area under the plasma concentration-time curve (AUC)0-t of CS1001
Timepoint [8] 0 0
From first dose to 30 days after last dose, up to 2 years
Secondary outcome [9] 0 0
Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Maximum plasma concentration (Cmax) of CS1001
Timepoint [9] 0 0
From first dose to 30 days after last dose, up to 2 years
Secondary outcome [10] 0 0
Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Time to reach maximum plasma concentration (Tmax) of CS1001
Timepoint [10] 0 0
From first dose to 30 days after last dose, up to 2 years
Secondary outcome [11] 0 0
Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Terminal elimination half-life (t1/2) of CS1001
Timepoint [11] 0 0
From first dose to 30 days after last dose, up to 2 years
Secondary outcome [12] 0 0
Phase Ib (Safety Evaluation) and/or Phase II (Efficacy Expansion): Clearance at Steady State (CLss) of CS1001
Timepoint [12] 0 0
From first dose to 30 days after last dose, up to 2 years
Secondary outcome [13] 0 0
Phase Ib (Safety Evaluation): Maximum plasma concentration (Cmax) of regorafenib
Timepoint [13] 0 0
From first dose to 30 days after last dose, up to 2 years
Secondary outcome [14] 0 0
Phase Ib (Safety Evaluation): Minimum plasma concentration (Cmin) of regorafenib
Timepoint [14] 0 0
From first dose to 30 days after last dose, up to 2 years

Eligibility
Key inclusion criteria
- All participants must have unresectable advanced or metastatic tumors that have
histologic or cytologic documentation confirmed.

- Participant must have at least one measurable lesion by CT or MRI per RECIST 1.1;
radiographic tumor assessment should be performed within 28 days prior to initiation
of study treatment.

- ECOG performance status score of 0 or 1.

- Life expectancy = 12 weeks.

- Fresh or archival tumor tissue must be provided for PD-L1 expression testing in
selected cohorts.

- Adequate organ function

- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test
result. Either Female or male participants must agree to use adequate contraceptive
measures from signing informed consent and for 180 days after last investigational
product administration, except for a participant with documented surgical
sterilization or a postmenopausal female.

- Any toxic effects of prior anti-cancer therapy or surgical procedures resolved to
baseline severity or NCI-CTCAE version 5 Grade 1 (except alopecia or other toxicities
not considered a safety risk for the patient at investigator's discretion).

- Subjects with hepatitis B virus (HBV) infection must have HBV DNA < 2000 IU/mL at
screening, and requires continue anti-HBV treatment in the study
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior malignancy active within the previous 3 years except for locally curable cancers
that have been apparently cured.

- Participants with any condition that impairs their ability to take oral medication,
such as lack of physical integrity of the upper gastrointestinal tract or
malabsorption syndrome.

- Has known central nervous system (CNS) metastases and/or carcinomatous meningitis that
is either symptomatic or untreated.

- Any prior (within 1 year) or current clinically significant ascites as measured by
physical examination and that requires active paracentesis for control.

- Significant history of cardiac disease within 6 months prior to Day 1 of Cycle 1,
myocardial infarction within the previous year, or current cardiac ventricular
arrhythmias requiring medication, or left ventricular ejection fraction (LVEF) is
below 50%.

- History or evidence of poorly controlled arterial hypertension.

- Any serious or uncontrolled medical disorder or active infection may increase the risk
associated with study participation or dose.

- Administration of drugs known as strong CYP3A4 inducers or strong CYP3A4 inhibitors
and the last dose was given in < 5 half-lives from the first investigational product
administration.

- Any hemorrhage or bleeding event = CTCAE Grade 3 within 28 days prior to the start of
study treatment.

Other inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/12/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/08/2021
Sample size
Target
Accrual to date
Final
19
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Ashford Cancer Centre Research - Kurralta Park
Recruitment postcode(s) [1] 0 0
5037 - Kurralta Park

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
CStone Pharmaceuticals
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Bayer
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a multicenter, open-label study of CS1001 in combination with regorafenib in
participants with advanced or refractory cancers. There will be a dose escalation portion in
"allcomers"to find a suitable dose of regorafenib for combination use with CS1001. This study
will also enroll participants with specific tumor types in the phase II part of the study to
assess the efficacy, pharmacokinetics and safety of the combined regimen (RP2D of regorafenib
+ CS 1001)
Trial website
https://clinicaltrials.gov/ct2/show/NCT04200404
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries