The ASCEND Study: Gemcitabine and Nab-Paclitaxel With CEND-1/LSTA1 or Placebo in Patients With Untreated Metastatic Pancreatic Ductal Adenocarcinoma

Pancreatic Ductal Adenocarcinoma Clinical Trial

— ASCEND  

Official title:

A Randomised, Double-blinded Phase II Study of Gemcitabine and Nab-Paclitaxel With CEND-1/LSTA1 or Placebo in Patients With Untreated Metastatic Pancreatic Ductal Adenocarcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05042128
• Other study ID #: CTC0304
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 13, 2022
• Est. completion date: October 1, 2024

Study information

• Verified date: April 2024
• Source: Australasian Gastro-Intestinal Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the ASCEND clinical trial is to measure the effect of adding CEND-1/LSTA1, compared to placebo, to chemotherapy (gemcitabine and nab-paclitaxel) in patients who have untreated metastatic pancreatic cancer. The study will assess the duration which the cancer remained stable or improved, the number of patients who responded to treatment, overall survival, side effects and quality of life.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 158
• Est. completion date: October 1, 2024
• Est. primary completion date: October 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults, 18 years or older with histologically confirmed metastatic pancreatic ductal adenocarcinoma or poorly differentiated carcinoma.
• Measurable disease according to RECIST 1.1.
• Archival tumour tissue for tertiary correlative studies (biopsy or resection of primary or metastasis). Fine needle aspirate (FNA) or brushings will not be accepted.
• ECOG performance of 0-1 (Appendix 2)
• Adequate renal and haematological function
• Adequate hepatic function, defined as:

Bilirubin <1.5 X ULN (Upper Limit of Normal), AST or ALT = 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.

• Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
• Study treatment both planned and able to start within 7 days after randomisation
• Signed, written informed consent.

Exclusion Criteria:

• 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.
• 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.
• Prior radiotherapy or major surgery (as defined by local investigator) within 14 days of starting treatment.
• Any unresolved toxicity 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 Grade =2 peripheral neuropathy are not allowed.
• Concurrent use of any other anti-cancer therapy including chemotherapy, targeted therapy, immunotherapy or biological agents.
• Known allergy or hypersensitivity to any of the study drugs and excipients.
• 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.
• History of prior or synchronous malignancy within 2 years prior to randomisation,

except:

1. Malignancy that was treated with curative intent and for which there has been no known active disease for =2 years prior to randomisation.

2. 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.

• Concurrent illness, including severe infection that may jeopardise the ability of the person to undergo the procedures outlined in this protocol with reasonable safety.
• Neuroendocrine pancreatic carcinoma.
• Life expectancy of less than 3 months.
• 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.
• Serious medical or psychiatric conditions that might limit the ability of the person to comply with the protocol.

Related Conditions & MeSH terms

• Adenocarcinoma
• Metastatic Pancreatic Cancer
• Pancreatic Ductal Adenocarcinoma

Intervention

Drug:
• CEND-1/LSTA1
CEND-1/LSTA1 is a novel cyclic tumour-penetrating peptide iRGD (internalizing Arginylglycylaspartic acid) which may overcome poor drug delivery by activation of a complex trans-tissue transport pathway, providing an opportunity to overcome this mechanism of resistance in PDAC
• Gemcitabine Injection
Chemotherapy drug provided as solution to be administered via IV infusion.
• Nab paclitaxel
Chemotherapy drug provided as solution to be administered via IV infusion.

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Adelaide	South Australia
Australia	Border Medical Oncology	Albury	New South Wales
Australia	Icon Cancer Centre Wesley	Auchenflower	Queensland
Australia	Sunshine Coast University Hospital	Birtinya	Queensland
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Monash Medical Centre	Clayton	New South Wales
Australia	Northern Health	Epping	Victoria
Australia	Lake Macquarie Private Hospital	Gateshead	New South Wales
Australia	Warringal Private Hospital	Heidelberg	Victoria
Australia	Royal Brisbane and Womens Hospital	Herston	Queensland
Australia	St George Hospital	Kogarah	New South Wales
Australia	Launceston General Hospital	Launceston	Tasmania
Australia	Frankston Hospital	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Calvary Mater Newcastle	Newcastle	New South Wales
Australia	Newcastle Private Hospital	Newcastle	New South Wales
Australia	Epworth Healthcare	Richmond	Victoria
Australia	ICON Cancer Centre, Gold Coast University Hospital	Southport	Queensland
Australia	St John of God	Subiaco	Western Australia
Australia	Prince of Wales Hospital	Sydney	New South Wales
Australia	Queen Elizabeth Hospital	Woodville South	South Australia
New Zealand	Dunedin Hospital	Dunedin
New Zealand	Waikato Hospital	Hamilton

Sponsors (2)

Lead Sponsor	Collaborator
Australasian Gastro-Intestinal Trials Group	University of Sydney

Countries where clinical trial is conducted

Australia,  New Zealand, 

References & Publications (1)

Dean A, Gill S, McGregor M, et al. 1528P Phase I trial of the first-in-class agent CEND-1 in combination with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer. Annals of Oncology 2020; 31: S941.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival	Period of time from randomization to the date of first evidence of disease progression, the occurrence of new disease or death from any cause	From date of randomization to 18 months later, or death
Secondary	Overall Survival	Period of time from randomization to date of death from any cause, or the date of last known follow-up alive	From date of randomization to 18 months later, or death
Secondary	Objective Tumour Response Rate	The number of participants with documented partial or complete response (PR or CR) divided by the number of participants evaluable for response as defined as per the RECIST version 1.1 criteria	From date of randomization to 18 months later, or death
Secondary	Patient-reported Outcomes	Completion of the EORTC QLQ-C30 questionnaire. 30 questions; 28 on a 1-4 scale (Higher scores indicative of poorer quality of life), 2 on a 1-7 scale (higher scores indicative of better health/quality of life).	Completed at baseline, then every 8 weeks from randomization until and at disease progression (to a maximum of 48 months).
Secondary	Patient-reported Outcomes	Completion of the QLQ-PAN26 questionnaire. 26 questions on a 1-4 scale (Higher scores indicative of poorer quality of life)	Completed at baseline, then every 8 weeks from randomization until and at disease progression (to a maximum of 48 months).
Secondary	Incidence of Treatment-Emergent Adverse Events (Patient Safety)	Record of all adverse events (including SAEs) that patients experience	From date of randomization until 30 days after final treatment visit