Clinical Trials /

L-DOS47 Plus Doxorubicin in Advanced Pancreatic Cancer

NCT04203641

Description:

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.

Related Conditions:
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: L-DOS47 Plus Doxorubicin in Advanced Pancreatic Cancer
  • Official Title: A Phase Ib/II Study of the Microenvironment Modifier L-DOS47 Plus Doxorubicin for the Treatment of Patients With Previously Treated Advanced Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: LDOS006
  • NCT ID: NCT04203641

Conditions

  • Pancreas Cancer

Interventions

DrugSynonymsArms
L-DOS47L-DOS47 + doxorubicin
DoxorubicinL-DOS47 + doxorubicin

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
L-DOS47 + doxorubicinExperimentalPatients 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.
  • L-DOS47
  • Doxorubicin

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of complete plus partial responders as per RECIST version 1.1
Time Frame:24 weeks
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Change in tumor pH
Time Frame:From screening to end of Cycle 2, where each treatment cycle is 28 days.
Safety Issue:
Description:Change from screening tumor pH as measured by SUV on fluorodeoxyglucose-positron emission tomography scan (FDG-PET) scan
Measure:Carbohydrate antigen (CA) 19-9 biomarker level
Time Frame:Up to 24 weeks
Safety Issue:
Description:Change from screening in CA19-9 biomarker levels
Measure:Proportion of patients expressing anti-L-DOS47 antibodies
Time Frame:Up to 24 weeks
Safety Issue:
Description:Assess number of patients expressing anti-L-DOS47 antibodies levels as a measure of

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Helix BioPharma Corporation

Trial Keywords

  • pancreatic cancer
  • immunoconjugate
  • tumor microenvironment alkalinization

Last Updated

December 17, 2019