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Trial registered on ANZCTR


Registration number
ACTRN12621001290886
Ethics application status
Approved
Date submitted
17/08/2021
Date registered
24/09/2021
Date last updated
21/01/2024
Date data sharing statement initially provided
24/09/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomised, double-blinded phase II study of gemcitabine and nab-paclitaxel with CEND-1 or placebo in patients with untreated metastatic pancreatic ductal adenocarcinoma
Scientific title
A Randomised, double-blinded phase II study of gemcitabine and nab-paclitaxel with CEND-1 or placebo in patients on progression-free survival in patients with untreated metastatic pancreatic ductal adenocarcinoma
Secondary ID [1] 305060 0
CTC0304
Universal Trial Number (UTN)
Trial acronym
ASCEND
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Pancreatic Ductal Adenocarcinoma 323266 0
Condition category
Condition code
Cancer 320837 320837 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will receive standard treatment of intravenous nab-paclitaxel (Dosage: 125mg/m2) and intravenous Gemcitabine (Dosage:1000mg/m2), on Day 1, 8 and 15 of each cycle. On each of these days, patients will also receive either intravenous CEND1 (3.2mg/kg IV) or an intravenous placebo.

Each cycle will be 28 days. Treatment will continue until disease progression, unacceptable toxicity, investigator decision, occurrence of condition affecting patient safety, required use of non-permitted comcomitant medication, patient decision, or failure to comply with protocol/study schedule. Site staff will monitor adherence to interventions from attendance information and discuss with investigator/coordinating centre to determine whether participation can continue.
Intervention code [1] 321455 0
Treatment: Drugs
Comparator / control treatment
A placebo, composed of 0.9% sodium chloride will be administered intravenously (Dosage: 3.2mg/kg ) on Day 1, 8 and 15 of each cycle. Each cycle will be 28 days.
Control group
Placebo

Outcomes
Primary outcome [1] 328633 0
Progression free survival (assessed via 8-weekly CT imaging on the chest, abdomen and pelvis, according to RECIST v1.1 criteria),
Timepoint [1] 328633 0
CT imaging conducted every 8 weeks (with a window of 1 week either side of the milestone) until progression is confirmed
Secondary outcome [1] 399760 0
Objective Tumour Response Rate assessed via 8-weekly CT imaging on the chest, abdomen and pelvis, according to RECIST v1.1 criteria, This rate is defined as the rate of participants with documented Complete Response or Partial Response, divided by the number of participants evaluable for response
Timepoint [1] 399760 0
Imaging performed every 8 weeks until progression or study closure (estimated maximum of 4 years)
Secondary outcome [2] 399761 0
Overall Survival
Timepoint [2] 399761 0
Updated at any point in the study while on treatment, and confirmed every 8 weeks while in follow-up for 18 months.
Secondary outcome [3] 399762 0
Patient-reported Outcomes as assessed by the EORTC QLQ-C30 Quality of Life Questionnaire
Timepoint [3] 399762 0
Assessed via patient questionnaires every 8 weeks while on study treatment until progression, at progression and at 30 days post-end of treatment
Secondary outcome [4] 399763 0
Patient-reported Outcomes as assessed by the EORTC QLQ-PAN26 Quality of Life Questionnaire
Timepoint [4] 399763 0
Assessed via patient questionnaires every 8 weeks while on study treatment until progression, at progression and at 30 days post-end of treatment
Secondary outcome [5] 400634 0
Patient Safety; participant will be asked by site staff at treatment and follow-up visits to report any adverse events that they have experienced since their previous visit
Timepoint [5] 400634 0
While on treatment; on day 1, 8 & 15 of the 28 day cycle until progression, then at 8-weekly follow-up visits for 18 months, or until death (whichever is first).

Eligibility
Key inclusion criteria
1. Adults, 18 years or older with histologically confirmed metastatic pancreatic ductal adenocarcinoma or poorly differentiated carcinoma.
2. Measurable disease according to RECIST 1.1.
3. Archival tumour tissue for tertiary correlative studies (biopsy or resection of primary or metastasis). Fine needle aspirate (FNA) or brushings will not be accepted.
4. ECOG performance of 0-1
5. Adequate renal and haematological function
6. Adequate hepatic function, defined as:
Bilirubin <1.5 X ULN (Upper Limit of Normal), AST or ALT greater than or equal to 5x ULN.
If a person was recently stented with improving bilirubin, the person can be randomised with bilirubin up to 3 x ULN provided chemotherapy is not administered until within the stated thresholds.
7. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
8. Study treatment both planned and able to start within 7 days after randomisation
9. Signed, written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Uncontrolled metastatic disease to the central nervous system. To be eligible, known CNS metastases should have been treated with surgery and/or radiotherapy and the patient should have been receiving a stable dose of steroids for at least 2 weeks prior to randomisation, with no deterioration in neurological symptoms during this time.
2. Prior chemotherapy or investigational anti-cancer therapy for metastatic pancreatic adenocarcinoma. Prior treatments with curative intent or for locally advanced disease are allowed, provided the last dose of chemotherapy was administered more than 6 months prior to randomisation.
3. Prior radiotherapy or major surgery (as defined by local investigator) within 14 days of starting treatment.
4. Any unresolved toxicity greater than or equal to NCI CTCAE Grade 2 from previous anti-cancer therapy with the exception of alopecia, vitiligo and the laboratory values defined in the inclusion criteria. Participants with greater than or equal to Grade peripheral neuropathy are not allowed.
5. Concurrent use of any other anti-cancer therapy including chemotherapy, targeted therapy, immunotherapy or biological agents.
6. Known allergy or hypersensitivity to any of the study drugs and excipients.
7. Any significant active infection, including chronic active hepatitis B, hepatitis C, or HIV. Participants with known Hepatitis B/C infection will be allowed to participate providing evidence of viral suppression has been documented and the patient remains on appropriate anti-viral therapy.
8. History of prior or synchronous malignancy within 2 years prior to randomisation, except:
a. Malignancy that was treated with curative intent and for which there has been no known active disease for greater than or equal to 2 years prior to randomisation.
b. Curatively treated non-melanoma skin cancer, cervical cancer in situ, superficial transitional cell carcinoma of the bladder, stage 1 endometrial carcinoma, prostatic intraepithelial neoplasia, low-grade papillary thyroid cancer, untreated localised very low risk or low risk prostate cancer under observation.
9. Concurrent illness, including severe infection that may jeopardise the ability of the person to undergo the procedures outlined in this protocol with reasonable safety.
10. Neuroendocrine pancreatic carcinoma.
11. Life expectancy of less than 3 months.
12. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to randomisation. Men must use a reliable means of contraception.
13. Serious medical or psychiatric conditions that might limit the ability of the person to comply with the protocol.

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Estimates of Progression Free Survival at 6 months will be calculated using the method of Kaplan-Meier and the corresponding 95% CI calculated. If the 6-month PFS rate in the gemcitabine/nab-paclitaxel (control) group are is ~47%, then activity will be declared if the lower boundary of a 95% one-sided CI for the combination gemcitabine/nab-paclitaxel + CEND-1 does not contain the control rate.

The EORTC QLQ-C30 will be scored according to the Scoring Manual using all available data. Missing items will be imputed using the scale mean, if more than 50% of the scale has been completed, as per the scoring manual. If less than 50% of a scale has been completed, it will be set to missing. Mean and range scale scores and will be calculated for each analysis group and plotted for each time point, by analysis group. Cock’s guidelines will be used to interpret the clinical relevance of changes in QLQ-C30 scores and a difference of 10 points will be used for other domains. Due to the sample size, which is sufficient for the primary endpoint, but insufficient for any statistical comparisons of PROs between groups across the numerous scales of the QLQ-C30 and QLQ-PAN26, analyses will be of a descriptive nature and will be detailed in a separate statistical analysis plan.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/02/2022
Actual
11/05/2022
Date of last participant enrolment
Anticipated
Actual
4/12/2023
Date of last data collection
Anticipated
30/06/2026
Actual
Sample size
Target
155
Accrual to date
Final
158
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 20256 0
St George Hospital - Kogarah
Recruitment hospital [2] 20257 0
Wollongong Hospital - Wollongong
Recruitment hospital [3] 20258 0
Nepean Hospital - Kingswood
Recruitment hospital [4] 20259 0
Prince of Wales Hospital - Randwick
Recruitment hospital [5] 20260 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [6] 20262 0
St John of God Hospital, Subiaco - Subiaco
Recruitment hospital [7] 20263 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [8] 20264 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [9] 20265 0
Border Medical Oncology - Albury
Recruitment hospital [10] 20266 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [11] 20267 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [12] 20268 0
Lake Macquarie Private Hospital - Gateshead
Recruitment hospital [13] 20269 0
Newcastle Private Hospital - New Lambton Heights
Recruitment hospital [14] 20272 0
Epworth Richmond - Richmond
Recruitment hospital [15] 20273 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [16] 20274 0
The Northern Hospital - Epping
Recruitment hospital [17] 20277 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [18] 23141 0
Warringal Private Hospital - Heidelberg
Recruitment hospital [19] 23387 0
Launceston General Hospital - Launceston
Recruitment hospital [20] 23388 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [21] 24590 0
Icon Cancer Care Wesley - Auchenflower
Recruitment postcode(s) [1] 34995 0
2217 - Kogarah
Recruitment postcode(s) [2] 34996 0
2500 - Wollongong
Recruitment postcode(s) [3] 34997 0
2747 - Kingswood
Recruitment postcode(s) [4] 34998 0
2031 - Randwick
Recruitment postcode(s) [5] 34999 0
5011 - Woodville
Recruitment postcode(s) [6] 35001 0
6008 - Subiaco
Recruitment postcode(s) [7] 35002 0
5042 - Bedford Park
Recruitment postcode(s) [8] 35003 0
6150 - Murdoch
Recruitment postcode(s) [9] 35004 0
2640 - Albury
Recruitment postcode(s) [10] 35005 0
2298 - Waratah
Recruitment postcode(s) [11] 35006 0
2050 - Camperdown
Recruitment postcode(s) [12] 35007 0
2290 - Gateshead
Recruitment postcode(s) [13] 35008 0
2305 - New Lambton Heights
Recruitment postcode(s) [14] 35011 0
3121 - Richmond
Recruitment postcode(s) [15] 35012 0
3168 - Clayton
Recruitment postcode(s) [16] 35013 0
3076 - Epping
Recruitment postcode(s) [17] 35016 0
4029 - Herston
Recruitment postcode(s) [18] 38500 0
3084 - Heidelberg
Recruitment postcode(s) [19] 38785 0
7250 - Launceston
Recruitment postcode(s) [20] 38786 0
4575 - Birtinya
Recruitment postcode(s) [21] 40185 0
4066 - Auchenflower
Recruitment outside Australia
Country [1] 25408 0
New Zealand
State/province [1] 25408 0
3204 - Waikato Hospital
Country [2] 25409 0
New Zealand
State/province [2] 25409 0
1023 -Auckland Hospital
Country [3] 25410 0
New Zealand
State/province [3] 25410 0
Dunedin Hospital

Funding & Sponsors
Funding source category [1] 309455 0
Commercial sector/Industry
Name [1] 309455 0
CEND Therapeutics
Country [1] 309455 0
United States of America
Primary sponsor type
Other Collaborative groups
Name
Australasian Gastro-Intestinal Cancer Trials Group
Address
GI Cancer Institute @Lifehouse
Level 6, 119-143 Missenden Rd
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 310430 0
None
Name [1] 310430 0
Address [1] 310430 0
Country [1] 310430 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309248 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 309248 0
King George V Building, Level 9, Missenden Rd, Camperdown NSW 2050
Ethics committee country [1] 309248 0
Australia
Date submitted for ethics approval [1] 309248 0
29/06/2021
Approval date [1] 309248 0
01/07/2021
Ethics approval number [1] 309248 0
2021/ETH00985

Summary
Brief summary
The ASCEND clinical trial aims to measure the effect of adding CEND-1 (a new cancer drug) or a placebo, to standard chemotherapy (gemcitabine and nab-paclitaxel) in patients who have untreated metastatic pancreatic cancer.

Who is it for?
You may be eligible for this study if you are aged 18 or older, you have been diagnosed with metastatic pancreatic ductal adenocarcinoma, and you have adequate liver and kidney function determined by blood tests.

Study details
Participants who choose to enrol in this study will be randomly allocated by chance (with 2/3 patients randomly assigned to the CEND-1 treatment) to receive either CEND1 in addition to the standard chemotherapy (gemcitabine and nab-paclitaxel), or a placebo in addition to the standard chemotherapy. Both CEND1 and the placebo will be administered by an intravenous infusion over a 28-day treatment cycle. Participants will continue to receive these treatments every 28 days until the cancer is seen to have progressed, or until treatment side effects become intolerable. Participants will undergo continuous monitoring for side effects throughout treatment, as well as completing questionnaires, blood tests and CT scans every 8 weeks for up to 18 months after starting the treatment.

It is hoped that this trial will provide information on whether CEND1 is safe and effective for the treatment of metastatic pancreatic cancer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113486 0
Prof Timothy Price
Address 113486 0
GI Cancer Institute @Lifehouse
Level 6, 119-143 Missenden Rd
Camperdown NSW 2050
Country 113486 0
Australia
Phone 113486 0
+61 8 8463 2500
Fax 113486 0
Email 113486 0
[email protected]
Contact person for public queries
Name 113487 0
Janet Tran
Address 113487 0
NHMRC CTC
Locked Bag 77
Camperdown NSW 1450
Country 113487 0
Australia
Phone 113487 0
+61 2 9562 5000
Fax 113487 0
Email 113487 0
[email protected]
Contact person for scientific queries
Name 113488 0
Janet Tran
Address 113488 0
NHMRC CTC
Locked Bag 77
Camperdown NSW 1450
Country 113488 0
Australia
Phone 113488 0
+61 2 9562 5000
Fax 113488 0
Email 113488 0
[email protected]

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

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIASCEND: a randomised, double-blinded, placebo-controlled, phase II study of gemcitabine and nab-paclitaxel with LSTA1 in untreated metastatic pancreatic adenocarcinoma. An Australasian Gastro-Intestinal Trials Group (AGITG) trial ?2023https://doi.org/10.1016/j.esmogo.2023.07.001
N.B. These documents automatically identified may not have been verified by the study sponsor.