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Trial registered on ANZCTR


Registration number
ACTRN12618000804280
Ethics application status
Approved
Date submitted
3/05/2018
Date registered
11/05/2018
Date last updated
9/12/2019
Date data sharing statement initially provided
18/01/2019
Date results information initially provided
9/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
CEND-1 in Combination With Nabpaclitaxel and Gemcitabine in Metastatic Pancreatic Cancer
Scientific title
A Phase 1 Clinical Trial of CEND-1 in Combination With Nabpaclitaxel and Gemcitabine in Metastatic Exocrine Pancreatic Cancer

Secondary ID [1] 294779 0
CEND1-001
Universal Trial Number (UTN)
U1111-1213-3234
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pancreatic cancer 307699 0
Condition category
Condition code
Cancer 306760 306760 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is an open-label, multicenter, dose-escalation, safety, pharmacodynamic, pharmacokinetic study of CEND-1 in combination with nabpaclitaxel and gemcitabine administered weekly for three weeks followed by one week off over 28 days.

This protocol is designed to evaluate the safety, tolerability, and biologic activity of CEND-1 in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who are undergoing a combination therapy with nabpaclitaxel and gemcitabine. CEND-1 is a tumor-penetrating peptide (scientifically also known as iRGD) that activates a drug transport mechanism specifically in tumors.

Study involves an initial dose escalation phase (1a) with four different CEND-1 dose levels, first as a monotherapy (during 1-week run-in), followed by a combination therapy with CEND-1 and nabpaclitaxel and gemcitabine (one 28-day treatment cycle). A subsequent expansion phase (1b) with approximately 28 subjects will assess the safety, tolerability and preliminary efficacy of the combination treatment using two different CEND-1 dose levels (14 subjects / dose level).

Cohort 1a (Dose Escalation):
Run-in Period (7 days)
- CEND-1 will be given intravenously as a slow IV push over 1 minute on day 1 of the run-in period.
Treatment Cycle 1
- On the second week after enrolling, treatment will commence with Cycle 1 of nabpaclitaxel followed by CEND-1 and gemcitabine (intravenous administration, one 28-day treatment cycle).

Cohort 1b (Safety/early efficacy):
Cohort 1b will explore safety and early efficacy with two CEND-1 dose levels (selected based on cohort 1a) in combination with nabpaclitaxel and gemcitabine (all agents intravenously).

Treatment cycles will be repeated every 4 weeks based on toxicity and response. Treatment may continue as long as there is perceived benefit or until disease progression. Study completion will be no later than when all patients have completed six (6) cycles. The Sponsor will continue to provide CEND-1 to patients who remain on active treatment without evidence of significant treatment-related toxicities or clinical evidence of progressive disease at study closure.
Intervention code [1] 301087 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 305748 0
Safe doses of CEND-1 when given alone or in combination with nabpaclitaxel and gemcitabine. Safety and toxicity profile of the treatment regimen as measured by grade and frequency of adverse events, graded and documented according to the NCI CTCAE, version 5.0 guidelines

Timepoint [1] 305748 0
Time Frame: Escalation Phase: From Day 1 of the run-in until Day 28 of Cycle 1 (cycle length=28 days)
Primary outcome [2] 305749 0
Optimal Biological Dose (OBD) of CEND-1 when given in combination with nabpaclitaxel and gemcitabine. OBD will be determined by evaluating the tumor marker CA19-9 Response Rate, the ECOG Performance Status, the Disease Control Rate and the Pharmacokinetics of CEND-1.
Timepoint [2] 305749 0
From baseline until treatment discontinuation and approximately 30 days after last dose.
Secondary outcome [1] 346358 0
Pharmacokinetics of plasma CEND-1 when given alone or in combination with nabpaclitaxel and gemcitabine. Area Under the Concentration-Time Curve of CEND-1 Following Intravenous (IV) Administration
Timepoint [1] 346358 0
Time Frame: Escalation phase: Predose, 3 minutes, 15 min, 30 min, 1 h, 4 h, 8 h postdose on Day 1 of the run-in and Day 1 of Cycle 1.
The change was made based on the PK analyzed from the first 5 patients (dose levels 1-3).
Secondary outcome [2] 346359 0
The disease control rate, i.e. the percentage of patients who have achieved Complete Remission (CR), Partial Remission (PR) and Stable disease (SD) associated with the administration of CEND-1 in combination with nabpaclitaxel and gemcitabine.

The radiological assessments of tumor for these outcome measures will be repeated every 2 cycles (8 weeks). A sum of the longest diameter (LD) for all target lesions will be calculated and reported as the baseline sum LD. The baseline sum LD will be used as reference by which to characterize the objective tumor response.

Definitions:
• Complete Response (CR): Disappearance of all target lesions
• Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD
• Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started







Timepoint [2] 346359 0
From baseline until treatment discontinuation and approximately 30 days after last dose.
Secondary outcome [3] 346360 0
To observe patients for any preliminary evidence of anti-tumor activity of CEND-1 when given in combination with nabpaclitaxel bound and gemcitabine by objective radiographic assessment according to RECIST 1.1.
Timepoint [3] 346360 0
From baseline until treatment discontinuation and approximately 30 days after last dose.

Eligibility
Key inclusion criteria
Patients with histologically confirmed metastatic pancreatic ductal carcinoma
One or more metastatic lesions measurable on MRI, PET/CT, or dedicated CT scan according to RECIST v1.1.
Eligible for treatment with nabpaclitaxel and gemcitabine
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Life expectancy of at least 3 months
Adequate archival tissue from prior biopsy for biomarker evaluation or willingness to undergo biopsy before treatment starts
The patient is capable of understanding and complying with the protocol and the subject or, when applicable, the subject's legally acceptable representative has signed the informed consent
A negative serum pregnancy test (if a premenopausal female patient)
Acceptable liver function: Bilirubin equal or less than 1.5 times upper limit of normal; AST (SGOT) less than 10 times upper limit of normal, ALT (SGPT) and Alkaline phosphatase equal or less than 2.5 times upper limit of normal (if liver metastases are present, then equal or less than 5 times upper limit is allowed).
Acceptable renal function: Serum creatinine within normal limits AND calculated creatinine clearance equal or more than 60 mL/min/1.73 per square meter for patients with creatinine levels above institutional normal by the Cockroft-Gault equation.
Acceptable hematologic status: Granulocyte equal or more than 1500 cells/mm3; Platelet count equal or more than 100,000 plt per square millimetre; Hemoglobin equal or more than 9 g/dL.
Urinalysis: No clinically significant abnormalities.
Acceptable coagulation status: PT within normal limits; PTT within normal limits.
For men and women of child-producing potential, the use of effective contraceptive methods during the study.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG
Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
Pregnant or nursing women. Women of child-bearing potential and men must agree to use adequate contraception.
Unwillingness or inability to comply with procedures required in this protocol
Known infection with HIV, hepatitis B, or hepatitis C
Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions per physician judgement) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor

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
Other
Other design features
Number of Arms: 2
Interventional Study Model: Sequential Assignment
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
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,WA,VIC
Recruitment hospital [1] 10828 0
St John of God Hospital, Subiaco - Subiaco
Recruitment hospital [2] 10829 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [3] 11613 0
The Alfred - Prahran
Recruitment postcode(s) [1] 22573 0
6008 - Subiaco
Recruitment postcode(s) [2] 22574 0
5011 - Woodville
Recruitment postcode(s) [3] 23656 0
3004 - Prahran
Recruitment postcode(s) [4] 23657 0
3181 - Prahran

Funding & Sponsors
Funding source category [1] 299386 0
Commercial sector/Industry
Name [1] 299386 0
DrugCendR Australia Pty Ltd
Address [1] 299386 0
58 Gipps Street, Collingwood, Victoria 3066
Country [1] 299386 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
DrugCendR Australia Pty Ltd
Address
58 Gipps Street, Collingwood, Victoria 3066
Country
Australia
Secondary sponsor category [1] 298669 0
None
Name [1] 298669 0
Address [1] 298669 0
Country [1] 298669 0
Other collaborator category [1] 280095 0
Commercial sector/Industry
Name [1] 280095 0
Novotech (Australia) Pty Ltd
Address [1] 280095 0
Level 3, 235 Pyrmont St
Pyrmont NSW 2009
Country [1] 280095 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300289 0
Concord Repatriation General Hospital
Ethics committee address [1] 300289 0
Concord Repatriation General Hospital
Hospital Road
Concord
NSW, 2139
Ethics committee country [1] 300289 0
Australia
Date submitted for ethics approval [1] 300289 0
27/03/2018
Approval date [1] 300289 0
Ethics approval number [1] 300289 0
Ethics committee name [2] 300349 0
Westmead Hospital
Ethics committee address [2] 300349 0
Westmead, New South Wales, Australia, 2145
Ethics committee country [2] 300349 0
Australia
Date submitted for ethics approval [2] 300349 0
27/03/2018
Approval date [2] 300349 0
Ethics approval number [2] 300349 0
Ethics committee name [3] 300350 0
Queen Elizabeth Hospital
Ethics committee address [3] 300350 0
Woodville South, South Australia, Australia, 5011
Ethics committee country [3] 300350 0
Australia
Date submitted for ethics approval [3] 300350 0
16/04/2018
Approval date [3] 300350 0
Ethics approval number [3] 300350 0
Ethics committee name [4] 300351 0
St John of God Hospital
Ethics committee address [4] 300351 0
Subiaco, Western Australia, Australia, 6008
Ethics committee country [4] 300351 0
Australia
Date submitted for ethics approval [4] 300351 0
10/05/2018
Approval date [4] 300351 0
12/07/2018
Ethics approval number [4] 300351 0

Summary
Brief summary
This is a phase 1 study of a new molecule (called CEND-1) designed to enter cancer cells and increase the uptake of chemotherapy drugs.

Who is it for?
You may be eligible for this study if you are aged over 18 and have histologically confirmed metastatic pancreatic ductal cancer.

Study details
Participants in the phase 1a of the study will take the study medication CEND-1 alone initially for one week, before commencing a combination therapy with CEND-1 and the 28-day cycle of chemotherapy. Participants in the phase 1b of the study will receive the combination therapy with CEND-1 and the 28-day cycle of chemotherapy directly. Treatment may continue as long as there is perceived benefit or until disease progression. All participants will provide blood samples and undergo imaging studies. All participants will receive standard doses of chemotherapy, nabpaclitaxel and gemcitabine, approved in Australia.

The primary goal of this research study is to find the correct dose of the study drug, CEND-1, that can be given alone or in combination with standard chemotherapy to patients with pancreatic cancer that has spread. Another goal is to measure the levels of CEND-1 in the blood over time. Researchers also want to learn if the study drug combinations can help to control the disease.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83170 0
Dr PHILIP BEALE
Address 83170 0
Concord Repatriation General Hospital
Hospital Road
Concord, NSW, 2139
Country 83170 0
Australia
Phone 83170 0
+61-2-97676354
Fax 83170 0
Email 83170 0
philip.beale@health.nsw.gov.au
Contact person for public queries
Name 83171 0
Dr Harri Jarvelainen
Address 83171 0
DrugCendR Pty Ltd.
50 Gipps Street
Collingwood Vic 3066
Country 83171 0
Australia
Phone 83171 0
+61 3 9016 3223
Fax 83171 0
Email 83171 0
info@drugcendr.com
Contact person for scientific queries
Name 83172 0
Dr Harri Jarvelainen
Address 83172 0
DrugCendR Pty Ltd
50 Gipps Street
Collingwood Vic 3066
Country 83172 0
Australia
Phone 83172 0
+61 3 9016 3223
Fax 83172 0
Email 83172 0
info@drugcendr.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Business reasons
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary