L-DOS47 Plus Doxorubicin in Advanced Pancreatic Cancer

NCT04203641 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: LDOS006
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

Brief Summary

This study will evaluate the safety and tolerability of escalating doses of L-DOS47 in combination with doxorubicin, as well as preliminary anti-tumor activity in patients with previously treated advanced pancreatic cancer.

Conditions

Pancreas Cancer

Keywords

pancreatic cancer; immunoconjugate; tumor microenvironment alkalinization

Outcome Measures

Primary Outcomes (2)

• Number of complete plus partial responders as per RECIST version 1.1

  Assess number of complete plus partial responders according to RECIST version 1.1 as a measure of preliminary anti-tumor activity of L-DOS47 in combination with doxorubicin

  24 weeks

• Adverse events (as per CTCAE v. 5.0)

  Assess frequency of treatment emergent adverse events as per Common Terminology Criteria for Adverse Events (CTCAE) v. 5 as a measure of safety and tolerability of L-DOS47 in combination with doxorubicin

  24 weeks

Secondary Outcomes (3)

• Change in tumor pH

  From screening to end of Cycle 2, where each treatment cycle is 28 days.

• Carbohydrate antigen (CA) 19-9 biomarker level

  Up to 24 weeks

• Proportion of patients expressing anti-L-DOS47 antibodies

  Up to 24 weeks

Study Arms (1)

L-DOS47 + doxorubicin

EXPERIMENTAL

Patients will be recruited into escalating dosing cohorts of 3, 6 and 9 µg/kg of L-DOS47, with a minimum of 3 and a maximum of 6 patients per cohort. A fixed dose of intravenous doxorubicin \[20 mg/m2/week\] will be administered in combination with L-DOS47 across all cohorts.

Biological: L-DOS47; Drug: Doxorubicin

Interventions

L-DOS47 BIOLOGICAL

A treatment cycle will be 28 days, with patients receiving L-DOS47 on Days 1, 8, 15, and 22.

L-DOS47 + doxorubicin

Doxorubicin DRUG

A treatment cycle will be 28 days, with patients receiving doxorubicin on Days 2, 9, 16 and 23

L-DOS47 + doxorubicin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged ≥ 18 years old
• One or more metastatic tumors measurable on computed tomography (CT) scan per RECIST version 1.1 and screening FDG-PET scan with maximum standardized uptake value (SUV max) ≥ 5.5 for at least one lesion consistent with pancreatic cancer.
• Karnofsky performance status ≥ 70%
• Life expectancy of at least 3 months
• Able to understand the information provided to them and to give written institutional review board (IRB)-approved informed consent prior to any study activities being conducted
• A negative pregnancy test (if of child bearing potential)
• Acceptable liver function:
• Bilirubin ≤ 1.5 times upper limit of normal
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Alkaline phosphatase (ALP) ≤ 2.5 times upper limit of normal (ULN; if liver metastases are present, then ≤ 5 x ULN is allowed)
• Acceptable renal function as defined by creatinine ≤1.5x institutional upper limits of normal, or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• Acceptable hematologic status:
• Granulocyte ≥ 1500 cells/mm3
• Platelet count ≥ 100,000 (plt/mm3)
• Hemoglobin ≥ 9g/dL
• Urinalysis:

You may not qualify if:

• 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
• Abnormal ejection fraction on ECHO or MUGA
• Active, uncontrolled bacterial, viral, or fungal infections requiring systematic therapy
• Pregnant or nursing women. NOTE: Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately.
• Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within 3 weeks prior to study entry
• Major surgery within 4 weeks prior to study entry
• Unwillingness or inability to comply with procedures required in this protocol
• Known infection with HIV, hepatitis B, or hepatitis C
• Serious nonmalignant disease (eg hydro nephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor
• Patients who are currently receiving any other investigational agent
• Patients with any evidence of uncontrolled brain metastases or carcinomatosis meningitis.
• Patients with marked screening prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval \> 480 milliseconds (CTCAE grade 1) using Fredericia's QT correction formula.

Sponsors & Collaborators

• Helix BioPharma Corporation: lead
• Theradex: collaborator

Study Sites (3)

Scottsdale Healthcare Hospitals DBA HonorHealth

Scottsdale, Arizona, 85260, United States

Location

Atlantic Health System, Morristown Medical Center

Morristown, New Jersey, 07962, United States

Location

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Doxorubicin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Erkut Borazanci, MD

  Scottsdale Healthcare Hospitals DBA HonorHealth

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label, single arm study that includes an initial three cohort dose escalation phase with 3, 6 and 9 µg/kg of L-DOS47 in combination with doxorubicin.

Study Record Dates

• First Submitted: September 16, 2019
• First Posted: December 18, 2019
• Study Start: December 11, 2019
• Primary Completion: October 24, 2024
• Study Completion: October 24, 2024
• Last Updated: May 6, 2025

Record last verified: 2024-10

Locations

US (3)