CEND-1 in Combination With Nabpaclitaxel and Gemcitabine in Metastatic Pancreatic Cancer

NCT ID: NCT03517176

Last Updated: 2024-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-31
• Study Completion Date: 2020-06-19

Brief Summary

CEND-1, Gemicitabine and Nab-Paclitaxel for Pancreatic Ductal Adenocarcinoma

Detailed Description

This is an open-label, multicenter, dose-escalation, safety, pharmacodynamic, pharmacokinetic study of CEND-1 in combination with nabpaclitaxel and gemcitabine administered weekly for three weeks followed by one week off over 28 days.

This protocol is designed to evaluate the safety, tolerability, and biologic activity of CEND-1 in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who are undergoing combination therapy with nabpaclitaxel and gemcitabine. CEND-1 is a tumor-penetrating peptide (scientifically also known as iRGD) that activates a drug transport mechanism specifically in tumors.

Study involves an initial dose escalation phase with four different CEND-1 dose levels, first as a monotherapy (during 1-week run-in), followed by combination therapy with nabpaclitaxel and gemcitabine (one 28-day treatment cycle). A subsequent expansion phase with approximately 28 subjects will assess the safety, tolerability and preliminary efficacy of the combination treatment using two different CEND-1 dose levels.

Conditions

Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A (Dose Escalation)

Safety of ascending dose levels of CEND-1 in combination with gemcitabine and nab-paclitaxel will be evaluated. Patients will receive an IV bolus of CEND-1 on Day 1 of the 1-week run-in period. This is followed by one treatment cycle (28 days) with the CEND-1 / nab-paclitaxel (125mg/m\^2) / gemcitabine (1000mg/m\^2) combination given on Days 1, 8, 15.

Group Type: EXPERIMENTAL

CEND-1

Intervention Type: DRUG

CEND-1 will be provided as concentrate for solution to be administered via IV injection.

Nab-paclitaxel

Intervention Type: DRUG

Nab-paclitaxel will be provided as solution to be administered via IV infusion.

Gemcitabine

Intervention Type: DRUG

Gemcitabine will be provided as solution to be administered via IV infusion.

Part B (Expansion)

Safety and early efficacy of CEND-1 in combination with nab-paclitaxel (125mg/m\^2) and gemcitabine (1000mg/m\^2) will be evaluated (dosing on Days 1, 8, 15 of the 28-day treatment cycle). Treatment cycles will be repeated every 4 weeks based on toxicity and response. Treatment may continue as long as there is perceived benefit or until disease progression.

Group Type: EXPERIMENTAL

CEND-1

Intervention Type: DRUG

CEND-1 will be provided as concentrate for solution to be administered via IV injection.

Nab-paclitaxel

Intervention Type: DRUG

Nab-paclitaxel will be provided as solution to be administered via IV infusion.

Gemcitabine

Intervention Type: DRUG

Gemcitabine will be provided as solution to be administered via IV infusion.

Interventions

CEND-1

CEND-1 will be provided as concentrate for solution to be administered via IV injection.

Intervention Type: DRUG

Nab-paclitaxel

Nab-paclitaxel will be provided as solution to be administered via IV infusion.

Intervention Type: DRUG

Gemcitabine

Gemcitabine will be provided as solution to be administered via IV infusion.

Intervention Type: DRUG

Other Intervention Names

LSTA1; certepetide; Abraxane; Gemzar

Eligibility Criteria

Inclusion Criteria

• Patients with histologically confirmed metastatic pancreatic ductal carcinoma
• One or more metastatic lesions measurable on MRI, PET/CT, or dedicated CT scan according to RECIST v1.1.
• Eligible for treatment with nabpaclitaxel and gemcitabine
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy of at least 3 months
• Adequate archival tissue from prior biopsy for biomarker evaluation or willingness to undergo biopsy before treatment starts
• The patient is capable of understanding and complying with the protocol and the subject or, when applicable, the subject's legally acceptable representative has signed the informed consent
• A negative serum pregnancy test (if a premenopausal female patient)
• Acceptable liver function: Bilirubin ≥ 1.5 times upper limit of normal; AST (SGOT) < 10 times upper limit of normal, ALT (SGPT) and Alkaline phosphatase 2.5 times upper limit of normal (if liver metastases are present, then ≤ 5 x ULN is allowed).
• Acceptable renal function: Serum creatinine within normal limits; calculated creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal by the Cockroft-Gault equation.
• Acceptable hematologic status: Granulocyte ≥ 1500 cells/mm3; Platelet count ≥ 100,000 plt/mm3; Hemoglobin ≥ 9 g/dL.
• Urinalysis: No clinically significant abnormalities.
• Acceptable coagulation status: PT within normal limits; PTT within normal limits.
• For men and women of child-producing potential, the use of effective contraceptive methods during the study.

Exclusion Criteria

• Prior chemotherapy or any other investigational agents for the treatment of pancreatic cancer.
• Concurrent use of any other anti-cancer therapy, including chemotherapy, targeted therapy, immunotherapy, or biological agents.
• Participants with known brain metastases.
• New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG.
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
• Pregnant or nursing women. Women of child-bearing potential and men must agree to use adequate contraception.
• Unwillingness or inability to comply with procedures required in this protocol.
• Known infection with HIV, hepatitis B, or hepatitis C.
• Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions per physician judgement) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor.

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

Sponsors

Lisata Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Alfred Hospital

Melbourne, Victoria, Australia

St John of God Hospital

Subiaco, Western Australia, Australia

Countries

Australia

References

Dean A, Gill S, McGregor M, Broadbridge V, Jarvelainen HA, Price T. Dual alphaV-integrin and neuropilin-1 targeting peptide CEND-1 plus nab-paclitaxel and gemcitabine for the treatment of metastatic pancreatic ductal adenocarcinoma: a first-in-human, open-label, multicentre, phase 1 study. Lancet Gastroenterol Hepatol. 2022 Oct;7(10):943-951. doi: 10.1016/S2468-1253(22)00167-4. Epub 2022 Jul 6.

Reference Type: DERIVED

PMID: 35803294 (View on PubMed)

Other Identifiers

U1111-1213-3234

Identifier Type: OTHER

Identifier Source: secondary_id

CEND1-001

Identifier Type: -

Identifier Source: org_study_id