CEND-1 In Combination With Nabpaclitaxel And Gemcitabine In Metastatic Pancreatic Cancer

Study Overview

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

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

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.

Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma

DRUG: CEND-1
DRUG: Nab-paclitaxel
DRUG: Gemcitabine

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

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2018-03-15	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-08-26
First Submitted that Met QC Criteria 2018-05-03	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-08-28
First Posted (ACTUAL) 2018-05-07	Results First Posted N/A	Last Verified 2024-08

Study Plan

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

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

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 CE	DRUG: CEND-1 CEND-1 will be provided as concentrate for solution to be administered via IV injection. DRUG: Nab-paclitaxel Nab-paclitaxel will be provided as solution to be administered via IV infusion. DRUG: Gemcitabine Gemcitabine will be provided as solution to be administered via IV infusion.
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 an	DRUG: CEND-1 CEND-1 will be provided as concentrate for solution to be administered via IV injection. DRUG: Nab-paclitaxel Nab-paclitaxel will be provided as solution to be administered via IV infusion. DRUG: Gemcitabine Gemcitabine will be provided as solution to be administered via IV infusion.

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 CE

DRUG: CEND-1

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

DRUG: Nab-paclitaxel

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

DRUG: Gemcitabine

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

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 an

DRUG: CEND-1

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

DRUG: Nab-paclitaxel

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

DRUG: Gemcitabine

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

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
Pharmacokinetics of CEND-1 when given alone or in combination with nabpaclitaxel and gemcitabine	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		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)

Contacts and Locations

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

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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.

Collaborators and Investigators

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

Publications

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

General Publications

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.

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Clinical Trial Record