Back to resultsA Phase I/II Open-Label, Non-Randomized Dose Escalation Study of Immunoconjugate L-DOS47
Primary Purpose
Non-Small Cell Lung Cancer
Status
Completed
Phase
Phase 1
Locations
Poland
Study Type
Interventional
Intervention
L-DOS47
Sponsored by
About this trial
This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring Non-Small Cell Lung Cancer, Neoplasms, Immunoconjugate, Tumor microenvironment alkalinization
Eligibility Criteria
Main Inclusion Criteria:
Patients will be entered in the study only if they meet all of the following criteria:
- Male or female aged ≥ 18 years old
Have histologically confirmed non-squamous NSCLC that are:
- Chemo naïve Stage IIIb or IV non-squamous NSCLC who are not candidates for chemotherapy or radiotherapy, or who refused standard therapy
- Refractory Stage IIIb or IV non-squamous NSCLC. (Staging of non-squamous NSCLC must be assessed according to TNM, 7th edition and based on computed tomography (CT) scan.)
- Have at least a single measurable lesion in accordance with the RECIST v1.1 criteria.
- Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
- Have a life expectancy of ≥ 3 months
- Have adequate bone marrow, renal and liver function
Main Exclusion Criteria:
- Are pregnant or nursing mother
- Have a prior history of other malignancies with the exception of non melanoma skin cancer
- Have known history of central nervous system (CNS) metastatic disease (previously treated or untreated)
- Show evidence of active infection
- Have received treatment in another clinical study within the 30 days before commencing study drug or have not recovered from side effects of a study drug, except for alopecia
- Have a serious uncontrolled medical condition
- Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen, or hepatitis C positive
- Sustained QTc (QT interval corrected for heart rate) with Fridericia's correction > 450 ms at screening, or a history of additional risk factors for Torsades de pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome)
- Pre-existing peripheral neuropathy ≥ CTC Grade 2
- Have dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent or compliance with the requirements of the protocol
- Are receiving chemotherapy during the 30 days before study treatment start; are receiving radiotherapy, targeted therapy, hormonal therapy, immunotherapy, major surgery or other study drugs during the 4 weeks before study treatment start, or have not recovered from all treatment related toxicities to Grade ≤ 1, except for alopecia. (Radiotherapy is allowed for the symptomatic treatment of bone metastases.)
- Are taking systemic steroids (other than inhalers or topical steroids) or other medication to suppress the immune system
- Are participating (or planning to participate) in any other clinical trial during this study.
Sites / Locations
- Mazovian Center of Pulmonary Diseases and Tuberculosis
- Med. Polonia Hospital Poznan
- Institute of Tuberculosis and Lung Diseases
- Military Medical Institute
- The Maria Sklodowska-Curie Memorial Cancer Centre & Institute of Oncology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
L-DOS47
Arm Description
Patient will be recruited into cohorts of L-DOS47 escalating doses, with a minimum of 3 and a maximum of 6 patients per cohort. The starting dose of L-DOS47 will be 0.12 μg/kg; further possible dose levels include 0.21, 0.33, 0.46, 0.59, 0.78, 1.04, 1.38, 1.84, 2.45, 3.26 and 4.33 μg/kg.
Outcomes
Primary Outcome Measures
The incidence and severity of drug-related adverse events as a measure of safety and tolerability of L-DOS47
Assessed during the AE reporting period starts on Cycle 1 Day 1 up to the last study visit.
Secondary Outcome Measures
L-DOS47 related toxicity during the first 2 hours after infusion
Assessed by the incidence and severity of AEs and SAEs and changes in vital signs
The incidence and severity of all reported adverse events and serious adverse events
Assessed during the AE reporting period starts on Cycle 1 Day 1 up to the last study visit.
Changes from baseline for additional safety parameters (clinical laboratory assessments, vital signs, weight, oxygen requirement and 12-lead ECG)
Safety parameters include clinical laboratory assessments, vital signs, weight, oxygen requirement and 12-lead ECG
The evaluation of anti-L-DOS47 antibody over time
Serum samples will be collected and analyzed from all patients dosed with L-DOS47.
Full Information
NCT ID
NCT02340208
First Posted
January 13, 2015
Last Updated
March 13, 2019
Sponsor
Helix BioPharma Corporation
Collaborators
Pharm-Olam International
1. Study Identification
Unique Protocol Identification Number
NCT02340208
Brief Title
A Phase I/II Open-Label, Non-Randomized Dose Escalation Study of Immunoconjugate L-DOS47
Official Title
A Phase I/II Open-Label, Non-Randomized Dose Escalation Study of Immunoconjugate L-DOS47 as a Monotherapy in Non-Squamous Non-Small Cell Lung Cancer Patients
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
August 1, 2017 (Actual)
Study Completion Date
December 20, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Helix BioPharma Corporation
Collaborators
Pharm-Olam International
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary purpose of this research study is to evaluate how safe, how well tolerated and how effective a range of doses of L-DOS47 in patients with non-squamous non-small cell lung cancer when given as a monotherapy.
Detailed Description
Patients will be recruited into cohorts, with a minimum of three and a maximum of six patients per cohort. All patients at a given dose level must complete Cycle 1 (3 week period) before escalation in subsequent patients can proceed. The decision for dose escalation to the next dose level will be made after the safety and available pharmacokinetic (PK) data have been reviewed by the Trial Steering Committee (TSC).
Escalation of L-DOS47 will continue until a maximum tolerated dose (MTD) is reached.
After the MTD of L-DOS47 has been determined in Phase I, up to 20 patients will be enrolled (taken forward from Phase I) to evaluate the preliminary efficacy of L-DOS47 (i.e., response rate using the Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1 criteria, disease progression and survival); monitoring will include radiologic evaluations every second cycle. The safety and tolerability of L-DOS47 will also be further evaluated. Pharmacokinetic information will be collected as well as relevant observations on the activity of L-DOS47.
For all patients, treatment with L-DOS47 will continue either until the patient experiences disease progression, unacceptable toxicity, the patient withdraws consent or has completed four treatment cycles and does not wish to continue with additional cycles, whichever occurs first. After four cycles, patients may continue to receive L-DOS47 for as long as there is sustained clinical benefit and it is well tolerated, in the opinion of the Investigator.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer
Keywords
Non-Small Cell Lung Cancer, Neoplasms, Immunoconjugate, Tumor microenvironment alkalinization
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
76 (Actual)
8. Arms, Groups, and Interventions
Arm Title
L-DOS47
Arm Type
Experimental
Arm Description
Patient will be recruited into cohorts of L-DOS47 escalating doses, with a minimum of 3 and a maximum of 6 patients per cohort. The starting dose of L-DOS47 will be 0.12 μg/kg; further possible dose levels include 0.21, 0.33, 0.46, 0.59, 0.78, 1.04, 1.38, 1.84, 2.45, 3.26 and 4.33 μg/kg.
Intervention Type
Drug
Intervention Name(s)
L-DOS47
Intervention Description
A treatment cycle will be 21 days with patients receiving L-DOS47 on cycle Days 1 and 8.
Primary Outcome Measure Information:
Title
The incidence and severity of drug-related adverse events as a measure of safety and tolerability of L-DOS47
Description
Assessed during the AE reporting period starts on Cycle 1 Day 1 up to the last study visit.
Time Frame
Up to 12 weeks
Secondary Outcome Measure Information:
Title
L-DOS47 related toxicity during the first 2 hours after infusion
Description
Assessed by the incidence and severity of AEs and SAEs and changes in vital signs
Time Frame
During the first 2 hours after infusion
Title
The incidence and severity of all reported adverse events and serious adverse events
Description
Assessed during the AE reporting period starts on Cycle 1 Day 1 up to the last study visit.
Time Frame
Participants will be followed for 12 weeks and the 30 day follow-up period
Title
Changes from baseline for additional safety parameters (clinical laboratory assessments, vital signs, weight, oxygen requirement and 12-lead ECG)
Description
Safety parameters include clinical laboratory assessments, vital signs, weight, oxygen requirement and 12-lead ECG
Time Frame
Up to 12 weeks
Title
The evaluation of anti-L-DOS47 antibody over time
Description
Serum samples will be collected and analyzed from all patients dosed with L-DOS47.
Time Frame
Up to 12 weeks
Other Pre-specified Outcome Measures:
Title
Maximum observed plasma concentration (Cmax) of L-DOS47 at each dose level
Description
Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patient dosed with L-DOS47.
Time Frame
Up to 12 weeks
Title
Time to maximum observed plasma concentration (Tmax) of L-DOS47 at each dose level
Description
Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patient dosed with L-DOS47.
Time Frame
Up to 12 weeks
Title
Area under the concentration (AUC) vs time curve of L-DOS47 at each dose level
Description
Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patient dosed with L-DOS47.
Time Frame
Up to 12 weeks
Title
Terminal elimination half-life of L-DOS47 at each dose level
Description
Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patient dosed with L-DOS47.
Time Frame
Up to 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main Inclusion Criteria:
Patients will be entered in the study only if they meet all of the following criteria:
Male or female aged ≥ 18 years old
Have histologically confirmed non-squamous NSCLC that are:
Chemo naïve Stage IIIb or IV non-squamous NSCLC who are not candidates for chemotherapy or radiotherapy, or who refused standard therapy
Refractory Stage IIIb or IV non-squamous NSCLC. (Staging of non-squamous NSCLC must be assessed according to TNM, 7th edition and based on computed tomography (CT) scan.)
Have at least a single measurable lesion in accordance with the RECIST v1.1 criteria.
Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
Have a life expectancy of ≥ 3 months
Have adequate bone marrow, renal and liver function
Main Exclusion Criteria:
Are pregnant or nursing mother
Have a prior history of other malignancies with the exception of non melanoma skin cancer
Have known history of central nervous system (CNS) metastatic disease (previously treated or untreated)
Show evidence of active infection
Have received treatment in another clinical study within the 30 days before commencing study drug or have not recovered from side effects of a study drug, except for alopecia
Have a serious uncontrolled medical condition
Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen, or hepatitis C positive
Sustained QTc (QT interval corrected for heart rate) with Fridericia's correction > 450 ms at screening, or a history of additional risk factors for Torsades de pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome)
Pre-existing peripheral neuropathy ≥ CTC Grade 2
Have dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent or compliance with the requirements of the protocol
Are receiving chemotherapy during the 30 days before study treatment start; are receiving radiotherapy, targeted therapy, hormonal therapy, immunotherapy, major surgery or other study drugs during the 4 weeks before study treatment start, or have not recovered from all treatment related toxicities to Grade ≤ 1, except for alopecia. (Radiotherapy is allowed for the symptomatic treatment of bone metastases.)
Are taking systemic steroids (other than inhalers or topical steroids) or other medication to suppress the immune system
Are participating (or planning to participate) in any other clinical trial during this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dariusz Kowalski, MD, PhD
Organizational Affiliation
The Maria Sklodowska-Curie Memorial Cancer Centre & Institute of Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mazovian Center of Pulmonary Diseases and Tuberculosis
City
Otwock
Country
Poland
Facility Name
Med. Polonia Hospital Poznan
City
Poznan
Country
Poland
Facility Name
Institute of Tuberculosis and Lung Diseases
City
Warsaw
Country
Poland
Facility Name
Military Medical Institute
City
Warsaw
Country
Poland
Facility Name
The Maria Sklodowska-Curie Memorial Cancer Centre & Institute of Oncology
City
Warsaw
Country
Poland
12. IPD Sharing Statement
Learn more about this trial
A Phase I/II Open-Label, Non-Randomized Dose Escalation Study of Immunoconjugate L-DOS47
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