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

Australasian Gastro-Intestinal Trials Group

Status and phase: Active, not recruiting; Phase 2

Conditions: Metastatic Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma

Treatments: Drug: Nab paclitaxel; Drug: LSTA1; Drug: Gemcitabine Injection

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT05042128

CTC0304

Details and patient eligibility

About

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.

Enrollment: 158 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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158 participants in 4 patient groups, including a placebo group

Cohort A: Standard Care + LSTA1 (1 dose)

Experimental group

Description:

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.

Treatment:

Drug: Gemcitabine Injection

Drug: LSTA1

Drug: Nab paclitaxel

Cohort A: Standard Care + Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Gemcitabine Injection

Drug: Nab paclitaxel

Cohort B: Standard Care +LSTA1 (2 doses)

Experimental group

Description:

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.

Treatment:

Drug: Gemcitabine Injection

Drug: LSTA1

Drug: Nab paclitaxel

Cohort B: Standard Care + Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Gemcitabine Injection

Drug: Nab paclitaxel