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

Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03517176
• Other study ID #: CEND1-001
• Secondary ID: U1111-1213-3234
• Status: Completed
• Phase: Phase 1
• Start date: July 31, 2018
• Est. completion date: June 19, 2020

Study information

• Verified date: July 2020
• Source: Lisata Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 19, 2020
• Est. primary completion date: June 19, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Ductal Adenocarcinoma
• Pancreatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
Australia	Alfred Hospital	Melbourne	Victoria
Australia	St John of God Hospital	Subiaco	Western Australia
Australia	Queen Elizabeth Hospital	Woodville South	South Australia

Sponsors (1)

Lead Sponsor	Collaborator
Lisata Therapeutics, Inc.

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	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)
Primary	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)
Primary	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	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
Secondary	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)
Secondary	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)