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

August 26, 2024 updated by: Lisata Therapeutics, Inc.

A Phase 1 Clinical Trial of CEND-1 in Combination With Nabpaclitaxel and Gemcitabine in Metastatic Exocrine Pancreatic Cancer

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • South Australia
      • Woodville South, South Australia, Australia, 5011
        • Queen Elizabeth Hospital
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • Alfred Hospital
    • Western Australia
      • Subiaco, Western Australia, Australia, 6008
        • St John of God Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: CEND-1
CEND-1 will be provided as concentrate for solution to be administered via IV injection.
Other Names:
  • LSTA1
  • certepetide
Drug: Nab-paclitaxel
Nab-paclitaxel will be provided as solution to be administered via IV infusion.
Other Names:
  • Abraxane
Drug: Gemcitabine
Gemcitabine will be provided as solution to be administered via IV infusion.
Other Names:
  • Gemzar
Experimental: 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.
Drug: CEND-1
CEND-1 will be provided as concentrate for solution to be administered via IV injection.
Other Names:
  • LSTA1
  • certepetide
Drug: Nab-paclitaxel
Nab-paclitaxel will be provided as solution to be administered via IV infusion.
Other Names:
  • Abraxane
Drug: Gemcitabine
Gemcitabine will be provided as solution to be administered via IV infusion.
Other Names:
  • Gemzar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safe doses of CEND-1 when given alone or in combination with nabpaclitaxel and gemcitabine
Time Frame: Escalation Phase: From Day 1 of the run-in until Day 28 of Cycle 1 (cycle length=28 days)
Safety and toxicity profile of treatment regimen as measured by grade and frequency of adverse events, graded and documented according to the NCI CTCAE, version 5.0 guidelines
Escalation Phase: From Day 1 of the run-in until Day 28 of Cycle 1 (cycle length=28 days)
Optimal Biological Dose (OBD) of CEND-1 when given in combination
Time Frame: Expansion Phase: from baseline until treatment discontinuation and approximately 30 days after last dose (cycle length=28 days)
OBD will be determined by evaluating biomarkers (such as the tumor marker CA19-9 Response Rate), the ECOG Performance Status and the Disease Control Rate
Expansion Phase: from baseline until treatment discontinuation and approximately 30 days after last dose (cycle length=28 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics of CEND-1 when given alone or in combination with nabpaclitaxel and gemcitabine
Time Frame: Escalation phase: Predose, 3 minutes, 15 min, 30 min, 1 h, 4 h, 8 h postdose on Day 1 of the run-in and Day 1 of Cycle 1
Area Under the Concentration-Time Curve of CEND-1 Following Intravenous (IV) Administration
Escalation phase: Predose, 3 minutes, 15 min, 30 min, 1 h, 4 h, 8 h postdose on Day 1 of the run-in and Day 1 of Cycle 1
Disease Control Rate (Complete Remission (CR) + Partial Remission (PR) + Stable Disease (SD)) associated with the administration of CEND-1 in combination with nabpaclitaxel and gemcitabine
Time Frame: Expansion Phase: from baseline until treatment discontinuation and approximately 30 days after last dose (cycle length=28 days)
Expansion Phase: from baseline until treatment discontinuation and approximately 30 days after last dose (cycle length=28 days)
Preliminary evidence of anti-tumor activity of CEND-1 when given in combination with nabpaclitaxel bound and gemcitabine by objective radiographic assessment according to RECIST 1.1
Time Frame: Expansion Phase: from baseline until treatment discontinuation and approximately 30 days after last dose (cycle length=28 days)
Expansion Phase: from baseline until treatment discontinuation and approximately 30 days after last dose (cycle length=28 days)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immunohistochemical assessment of tumor biopsies for the expression of Neuropilin-1 in order to study if the response to CEND-1 therapy can be predicted based on the Neuropilin-1 expression level
Time Frame: Screening Phase (Day -14 until Day -1)
Analysis of paraffin-embedded tumor tissues (also potentially in liquid-nitrogen frozen tissue, if available) will be performed to characterize Neuropilin-1 expression by immunohistochemistry (IHC) and potentially other analysis techniques.
Screening Phase (Day -14 until Day -1)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lisata Therapeutics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 31, 2018

Primary Completion (Actual)

June 19, 2020

Study Completion (Actual)

June 19, 2020

Study Registration Dates

First Submitted

March 15, 2018

First Submitted That Met QC Criteria

May 3, 2018

First Posted (Actual)

May 7, 2018

Study Record Updates

Last Update Posted (Actual)

August 28, 2024

Last Update Submitted That Met QC Criteria

August 26, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CEND1-001
  • U1111-1213-3234 (Other Identifier: The Universal Trial Number (UTN))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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