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L-DOS47 Plus Doxorubicin in Advanced Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04203641
Recruitment Status : Recruiting
First Posted : December 18, 2019
Last Update Posted : April 13, 2021
Information provided by (Responsible Party):
Helix BioPharma Corporation

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.

Condition or disease Intervention/treatment Phase
Pancreas Cancer Biological: L-DOS47 Drug: Doxorubicin Phase 1 Phase 2

Detailed Description:

The Phase Ib part of the study will apply a standard 3 + 3 algorithm for dose escalation to determine the appropriate L-DOS47 maximum tolerated dose to use in combination with doxorubicin for the Phase II part of the study. Patients will be recruited into 3 cohorts where each cohort will receive increasing weekly dose levels of L-DOS47 in combination with a fixed dose of 20 mg/m2 of doxorubicin weekly. The decision for escalation to the next dose level will be made after all patients in a cohort have completed 4 weeks of combination treatment and the safety data have been reviewed by the Safety Review Committee. If a patient in any cohort experiences a dose limiting toxicity, an additional 3 patients will be enrolled, for a maximum of up to 18 patients in this initial dose escalation part of the study.

The Phase II part of the study will focus on evaluating preliminary anti-tumor activity, as well as continuing to evaluate safety and tolerability of L-DOS47 in combination with doxorubicin. A further 11 additional patients will be enrolled in this phase of the study, which is designed to ensure patient safety and to detect whether there is a level of anti-tumor activity that would be worth pursuing in a larger clinical trial. Patients will be initiated on the L-DOS47 dose determined in Phase I, in combination with 20 mg/m2 doxorubicin, with tumor marker carbohydrate antigen 19-9 (CA19-9) measurements at each treatment cycle, and radiological assessments every two treatment cycles.

Tumor response will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.

Safety will be assessed by reported adverse events (AEs), serious adverse events (SAEs), physical exams, vital signs, Karnofsky Performance Status, electrocardiogram (ECG), echocardiogram (ECHO)/multigated acquisition scan (MUGA), clinical laboratory evaluations (hematology, chemistry, coagulation and urinalysis), and anti-L-DOS47 antibody levels.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Study of the Microenvironment Modifier L-DOS47 Plus Doxorubicin for the Treatment of Patients With Previously Treated Advanced Pancreatic Cancer
Actual Study Start Date : December 11, 2019
Estimated Primary Completion Date : October 31, 2021
Estimated Study Completion Date : October 31, 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: L-DOS47 + doxorubicin
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
A treatment cycle will be 28 days, with patients receiving L-DOS47 on Days 1, 8, 15, and 22.

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

Primary Outcome Measures :
  1. Number of complete plus partial responders as per RECIST version 1.1 [ Time Frame: 24 weeks ]
    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

  2. Adverse events (as per CTCAE v. 5.0) [ Time Frame: 24 weeks ]
    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

Secondary Outcome Measures :
  1. Change in tumor pH [ Time Frame: From screening to end of Cycle 2, where each treatment cycle is 28 days. ]
    Change from screening tumor pH as measured by SUV on fluorodeoxyglucose-positron emission tomography scan (FDG-PET) scan

  2. Carbohydrate antigen (CA) 19-9 biomarker level [ Time Frame: Up to 24 weeks ]
    Change from screening in CA19-9 biomarker levels

  3. Proportion of patients expressing anti-L-DOS47 antibodies [ Time Frame: Up to 24 weeks ]
    Assess number of patients expressing anti-L-DOS47 antibodies levels as a measure of

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male or female aged ≥ 18 years old
  2. 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.
  3. Karnofsky performance status ≥ 70%
  4. Life expectancy of at least 3 months
  5. 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
  6. A negative pregnancy test (if of child bearing potential)
  7. Acceptable liver function:

    1. Bilirubin ≤ 1.5 times upper limit of normal
    2. 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)
  8. 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
  9. Acceptable hematologic status:

    1. Granulocyte ≥ 1500 cells/mm3
    2. Platelet count ≥ 100,000 (plt/mm3)
    3. Hemoglobin ≥ 9g/dL
  10. Urinalysis:

    a) No clinically significant abnormalities

  11. Acceptable coagulation status

    1. Prothrombin time within 1.5x of normal limits
    2. Partial thromboplastin time (PTT) within 1.5x of normal limits
  12. For men and women of child-bearing potential, the use of effective contraceptive methods during the study
  13. Normal ejection fraction on ECHO or MUGA

Exclusion Criteria:

  1. 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
  2. Abnormal ejection fraction on ECHO or MUGA
  3. Active, uncontrolled bacterial, viral, or fungal infections requiring systematic therapy
  4. 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.
  5. Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within 3 weeks prior to study entry
  6. Major surgery within 4 weeks prior to study entry
  7. Unwillingness or inability to comply with procedures required in this protocol
  8. Known infection with HIV, hepatitis B, or hepatitis C
  9. 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
  10. Patients who are currently receiving any other investigational agent
  11. Patients with any evidence of uncontrolled brain metastases or carcinomatosis meningitis.
  12. 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.

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 identifier (NCT number): NCT04203641

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Contact: Heman Chao, Ph.D. 905-841-2300 ext 235
Contact: Brenda Lee, M.Sc. 416-809-2101

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United States, Arizona
Scottsdale Healthcare Hospitals DBA HonorHealth Recruiting
Scottsdale, Arizona, United States, 85260
Contact: Erkut Borazanci, MD         
Contact: Joyce Schaffer, RN    480-323-1364   
United States, New Jersey
Atlantic Health System, Morristown Medical Center Recruiting
Morristown, New Jersey, United States, 07962
Contact: Nancy Ginder, BSN, OCN    973-971-6608   
United States, Wisconsin
Froedtert Hospital and the Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: General Cancer Center Information    866-680-0505 ext 8900   
Contact    414-805-8900      
Sponsors and Collaborators
Helix BioPharma Corporation
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Principal Investigator: Erkut Borazanci, MD Scottsdale Healthcare Hospitals DBA HonorHealth
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Responsible Party: Helix BioPharma Corporation Identifier: NCT04203641    
Other Study ID Numbers: LDOS006
First Posted: December 18, 2019    Key Record Dates
Last Update Posted: April 13, 2021
Last Verified: April 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Helix BioPharma Corporation:
pancreatic cancer
tumor microenvironment alkalinization
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action