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

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ClinicalTrials.gov Identifier: NCT03517176
Recruitment Status : Recruiting
First Posted : May 7, 2018
Last Update Posted : January 1, 2019
Sponsor:
Information provided by (Responsible Party):
DrugCendR Inc.

Study Description
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Brief Summary:
CEND-1, Gemicitabine and Nab-Paclitaxel for Pancreatic Ductal Adenocarcinoma

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Pancreatic Ductal Adenocarcinoma Drug: CEND-1 Drug: Nab-paclitaxel Drug: Gemcitabine Phase 1

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Clinical Trial of CEND-1 in Combination With Nabpaclitaxel and Gemcitabine in Metastatic Exocrine Pancreatic Cancer
Actual Study Start Date : July 31, 2018
Estimated Primary Completion Date : October 1, 2019
Estimated Study Completion Date : December 30, 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: iRGD

Drug: Nab-paclitaxel
Nab-paclitaxel will be provided as solution to be administered via IV infusion.
Other Name: Abraxane

Drug: Gemcitabine
Gemcitabine will be provided as solution to be administered via IV infusion.
Other Name: 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 Name: iRGD

Drug: Nab-paclitaxel
Nab-paclitaxel will be provided as solution to be administered via IV infusion.
Other Name: Abraxane

Drug: Gemcitabine
Gemcitabine will be provided as solution to be administered via IV infusion.
Other Name: Gemzar


Outcome Measures
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Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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

  2. 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) ]
  3. 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 Outcome Measures:
  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 [ 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03517176


Contacts
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Contact: DrugCendR Call Center 8586463100 info@drugcendr.com

Locations
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Australia, New South Wales
Concord Repatriation General Hospital Recruiting
Concord, New South Wales, Australia, 2139
Contact: Philip Beale         
Australia, South Australia
Queen Elizabeth Hospital Recruiting
Woodville South, South Australia, Australia, 5011
Contact: Timothy Price         
Australia, Victoria
Alfred Hospital Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Sanjeev Gill         
Australia, Western Australia
St John of God Hospital Recruiting
Subiaco, Western Australia, Australia, 6008
Contact: Andrew Dean         
Sponsors and Collaborators
DrugCendR Inc.
More Information
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Responsible Party: DrugCendR Inc.
ClinicalTrials.gov Identifier: NCT03517176     History of Changes
Other Study ID Numbers: CEND1-001
U1111-1213-3234 ( Other Identifier: The Universal Trial Number (UTN) )
First Posted: May 7, 2018    Key Record Dates
Last Update Posted: January 1, 2019
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Gemcitabine
 Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs