The ASCEND Study: Gemcitabine and Nab-Paclitaxel With LSTA1 (Certepetide) or Placebo in Patients With Untreated Metastatic Pancreatic Ductal Adenocarcinoma

NCT ID: NCT05042128

Last Updated: 2024-10-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 158 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-13
• Study Completion Date: 2025-10-01

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.

Conditions

Pancreatic Ductal Adenocarcinoma; Metastatic Pancreatic Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Cohort A: Standard Care + LSTA1 (1 dose)

Participants will receive nab-paclitaxel 125mg/m2; LSTA1 3.2mg/kg IV; and then Gemcitabine 1000mg/m2, on Day 1, 8 and 15 of each cycle. Each cycle will be 28 days.

Group Type: EXPERIMENTAL

LSTA1

Intervention Type: DRUG

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

Intervention Type: DRUG

Chemotherapy drug provided as solution to be administered via IV infusion.

Nab paclitaxel

Intervention Type: DRUG

Chemotherapy drug provided as solution to be administered via IV infusion.

Cohort A: Standard Care + Placebo

Participants will receive nab-paclitaxel 125mg/m2; placebo IV; and then Gemcitabine 1000mg/m2, on Day 1, 8 and 15 of each cycle. Each cycle will be 28 days.

Group Type: PLACEBO_COMPARATOR

Gemcitabine Injection

Intervention Type: DRUG

Chemotherapy drug provided as solution to be administered via IV infusion.

Nab paclitaxel

Intervention Type: DRUG

Chemotherapy drug provided as solution to be administered via IV infusion.

Cohort B: Standard Care +LSTA1 (2 doses)

Participants will receive nab-paclitaxel 125mg/m2; LSTA1 3.2mg/kg IV; Gemcitabine 1000mg/m2, and then +\~4hrs LSTA1 3.2mg/kg IV on Day 1, 8 and 15 of each cycle. Each cycle will be 28 days.

Group Type: EXPERIMENTAL

LSTA1

Intervention Type: DRUG

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

Intervention Type: DRUG

Chemotherapy drug provided as solution to be administered via IV infusion.

Nab paclitaxel

Intervention Type: DRUG

Chemotherapy drug provided as solution to be administered via IV infusion.

Cohort B: Standard Care + Placebo

Participants will receive nab-paclitaxel 125mg/m2; placebo IV; Gemcitabine 1000mg/m2, and then +\~4hrs matching placebo IV on Day 1, 8 and 15 of each cycle. Each cycle will be 28 days.

Group Type: PLACEBO_COMPARATOR

Gemcitabine Injection

Intervention Type: DRUG

Chemotherapy drug provided as solution to be administered via IV infusion.

Nab paclitaxel

Intervention Type: DRUG

Chemotherapy drug provided as solution to be administered via IV infusion.

Interventions

LSTA1

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

Intervention Type: DRUG

Gemcitabine Injection

Chemotherapy drug provided as solution to be administered via IV infusion.

Intervention Type: DRUG

Nab paclitaxel

Chemotherapy drug provided as solution to be administered via IV infusion.

Intervention Type: DRUG

Other Intervention Names

CEND-1, certepetide; Gemzar; Abraxane

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.

• 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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Sydney

OTHER

Sponsor Role: collaborator

Australasian Gastro-Intestinal Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew Dean

Role: STUDY_CHAIR

St John of God Hospital

Timothy Price

Role: STUDY_CHAIR

The Queen Elizabeth Hospital

Locations

Border Medical Oncology

Albury, New South Wales, Australia

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Monash Medical Centre

Clayton, New South Wales, Australia

Lake Macquarie Private Hospital

Gateshead, New South Wales, Australia

St George Hospital

Kogarah, New South Wales, Australia

Calvary Mater Newcastle

Newcastle, New South Wales, Australia

Newcastle Private Hospital

Newcastle, New South Wales, Australia

Prince of Wales Hospital

Sydney, New South Wales, Australia

Icon Cancer Centre Wesley

Auchenflower, Queensland, Australia

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

Royal Brisbane and Womens Hospital

Herston, Queensland, Australia

ICON Cancer Centre, Gold Coast University Hospital

Southport, Queensland, Australia

Flinders Medical Centre

Adelaide, South Australia, Australia

Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Launceston General Hospital

Launceston, Tasmania, Australia

Northern Health

Epping, Victoria, Australia

Warringal Private Hospital

Heidelberg, Victoria, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Frankston Hospital

Melbourne, Victoria, Australia

Epworth Healthcare

Richmond, Victoria, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

St John of God

Subiaco, Western Australia, Australia

Dunedin Hospital

Dunedin, , New Zealand

Waikato Hospital

Hamilton, , New Zealand

Countries

Australia; New Zealand

References

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.

Reference Type: BACKGROUND

Other Identifiers

CTC0304

Identifier Type: -

Identifier Source: org_study_id