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

• ClinicalTrials.gov Identifier: NCT03517176
• Recruitment Status: Completed
• First Posted: May 7, 2018
• Last Update Posted: October 27, 2020
• Sponsor: DrugCendR Inc.
• Information provided by (Responsible Party): DrugCendR Inc.

Study Description

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 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
• Actual Primary Completion Date: June 19, 2020
• Actual Study Completion Date: June 19, 2020

Arms and Interventions

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

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

• 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

Locations

Australia, South Australia

Queen Elizabeth Hospital

Woodville South, South Australia, Australia, 5011

Australia, Victoria

Alfred Hospital

Melbourne, Victoria, Australia, 3004

Australia, Western Australia

St John of God Hospital

Subiaco, Western Australia, Australia, 6008

Sponsors and Collaborators

DrugCendR Inc.

More Information

• Responsible Party: DrugCendR Inc.
• ClinicalTrials.gov Identifier: NCT03517176
• Other Study ID Numbers: CEND1-001; U1111-1213-3234 ( Other Identifier: The Universal Trial Number (UTN) )
• First Posted: May 7, 2018
• Last Update Posted: October 27, 2020
• Last Verified: July 2020

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

Additional relevant MeSH terms:

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