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

Primary Purpose

Pancreatic Cancer, Pancreatic Ductal Adenocarcinoma

Status

Completed

Phase

Phase 1

Locations

Australia

Study Type

Interventional

Intervention

CEND-1

Nab-paclitaxel

Gemcitabine

About this trial

This is an interventional treatment trial for Pancreatic Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Queen Elizabeth Hospital
Alfred Hospital
St John of God Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Part A (Dose Escalation)

Part B (Expansion)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

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

Secondary Outcome Measures

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

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

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

Full Information

NCT ID

NCT03517176

First Posted

March 15, 2018

Last Updated

October 26, 2022

Sponsor

Lisata Therapeutics, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03517176

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

July 31, 2018 (Actual)

Primary Completion Date

June 19, 2020 (Actual)

Study Completion Date

June 19, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Lisata Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreatic Cancer, Pancreatic Ductal Adenocarcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A (Dose Escalation)

Arm Type

Experimental

Arm Description

Arm Title

Part B (Expansion)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

CEND-1

Other Intervention Name(s)

iRGD

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Nab-paclitaxel

Other Intervention Name(s)

Abraxane

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Other Intervention Name(s)

Gemzar

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

Escalation Phase: From Day 1 of the run-in until Day 28 of Cycle 1 (cycle length=28 days)

Title

Optimal Biological Dose (OBD) of CEND-1 when given in combination

Description

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

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

Area Under the Concentration-Time Curve of CEND-1 Following Intravenous (IV) Administration

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

Title

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)

Title

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)

Other Pre-specified Outcome Measures:

Title

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

Description

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.

Time Frame

Screening Phase (Day -14 until Day -1)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Facility Information:

Facility Name

Queen Elizabeth Hospital

City

Woodville South

State/Province

South Australia

ZIP/Postal Code

5011

Country

Australia

Facility Name

Alfred Hospital

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3004

Country

Australia

Facility Name

St John of God Hospital

City

Subiaco

State/Province

Western Australia

ZIP/Postal Code

6008

Country

Australia

12. IPD Sharing Statement

Citations:

PubMed Identifier

35803294

Citation

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.

Results Reference

derived

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

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