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

NCT03517176 | Completed Phase 1 DMC

• 2 other identifiers: CEND1-001U1111-1213-3234
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Safe doses of CEND-1 when given alone or in combination with nabpaclitaxel and gemcitabine

  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

  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 Outcomes (3)

• Pharmacokinetics of CEND-1 when given alone or in combination with nabpaclitaxel and gemcitabine

  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

  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

  Expansion Phase: from baseline until treatment discontinuation and approximately 30 days after last dose (cycle length=28 days)

Other Outcomes (1)

• 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

  Screening Phase (Day -14 until Day -1)

Study Arms (2)

Part A (Dose Escalation)

EXPERIMENTAL

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; Drug: Nab-paclitaxel; Drug: Gemcitabine

Part B (Expansion)

EXPERIMENTAL

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; Drug: Nab-paclitaxel; Drug: Gemcitabine

Interventions

CEND-1 DRUG

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

Also known as: LSTA1, certepetide

Part A (Dose Escalation); Part B (Expansion)

Nab-paclitaxel DRUG

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

Also known as: Abraxane

Part A (Dose Escalation); Part B (Expansion)

Gemcitabine DRUG

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

Also known as: Gemzar

Part A (Dose Escalation); Part B (Expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lisata Therapeutics, Inc.: lead

Study Sites (3)

Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

St John of God Hospital

Subiaco, Western Australia, 6008, Australia

Location

Related Publications (1)

• 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.

  PMID: 35803294 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2018
• First Posted: May 7, 2018
• Study Start: July 31, 2018
• Primary Completion: June 19, 2020
• Study Completion: June 19, 2020
• Last Updated: August 28, 2024

Record last verified: 2024-08

Locations

AU (3)