Clinical trial NCT05042128: The ASCEND Study: Gemcitabine and Nab-Paclitaxel With LSTA1 (Certepetide) or Placebo in Patients With Untreated Metastatic Pancreatic Ductal Adenocarcinoma
Official title: A Randomised, Double-blinded Phase II Study of Gemcitabine and Nab-Paclitaxel With LSTA1 (Certepetide) or Placebo in Patients With Untreated Metastatic Pancreatic Ductal Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Pancreatic Ductal Adenocarcinoma
Metastatic Pancreatic Cancer
Lead sponsor: Australasian Gastro-Intestinal Trials Group
Sponsor class: NETWORK
Collaborators: name: University of Sydney
First posted: 2021-09-13
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the ASCEND clinical trial is to measure the effect of adding LSTA1 (certepetide), 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival
timeFrame: From date of randomization to 18 months later, or death
Secondary outcomes:
measure: Overall Survival
timeFrame: From date of randomization to 18 months later, or death
measure: Objective Tumour Response Rate
timeFrame: From date of randomization to 18 months later, or death
measure: Patient-reported Outcomes
timeFrame: Completed at baseline, then every 8 weeks from randomization until and at disease progression (to a maximum of 48 months).
measure: Patient-reported Outcomes
timeFrame: Completed at baseline, then every 8 weeks from randomization until and at disease progression (to a maximum of 48 months).
measure: Incidence of Treatment-Emergent Adverse Events (Patient Safety)
timeFrame: From date of randomization until 30 days after final treatment visit
Other outcomes:
Locations:
city: Albury
country: Australia
facility: Border Medical Oncology
state: New South Wales
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Clayton
country: Australia
facility: Monash Medical Centre
state: New South Wales
city: Gateshead
country: Australia
facility: Lake Macquarie Private Hospital
state: New South Wales
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Newcastle
country: Australia
facility: Newcastle Private Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Auchenflower
country: Australia
facility: Icon Cancer Centre Wesley
state: Queensland
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Womens Hospital
state: Queensland
city: Southport
country: Australia
facility: ICON Cancer Centre, Gold Coast University Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Woodville South
country: Australia
facility: Queen Elizabeth Hospital
state: South Australia
city: Launceston
country: Australia
facility: Launceston General Hospital
state: Tasmania
city: Epping
country: Australia
facility: Northern Health
state: Victoria
city: Heidelberg
country: Australia
facility: Warringal Private Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Frankston Hospital
state: Victoria
city: Richmond
country: Australia
facility: Epworth Healthcare
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Subiaco
country: Australia
facility: St John of God
state: Western Australia
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
Study officials:
affiliation: St John of God Hospital
name: Andrew Dean
role: STUDY_CHAIR
affiliation: The Queen Elizabeth Hospital
name: Timothy Price
role: STUDY_CHAIR
References:
citation: 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.