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A Phase I/II Open-Label, Non-Randomized Dose Escalation Study of Immunoconjugate L-DOS47

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02340208
Recruitment Status : Completed
First Posted : January 16, 2015
Last Update Posted : March 14, 2019
Sponsor:
Collaborator:
Pharm-Olam International
Information provided by (Responsible Party):
Helix BioPharma Corporation

Tracking Information
First Submitted Date  ICMJE January 13, 2015
First Posted Date  ICMJE January 16, 2015
Last Update Posted Date March 14, 2019
Study Start Date  ICMJE May 2012
Actual Primary Completion Date August 1, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 15, 2015)
The incidence and severity of drug-related adverse events as a measure of safety and tolerability of L-DOS47 [ Time Frame: Up to 12 weeks ]
Assessed during the AE reporting period starts on Cycle 1 Day 1 up to the last study visit.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2015)
  • L-DOS47 related toxicity during the first 2 hours after infusion [ Time Frame: 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 [ Time Frame: Participants will be followed for 12 weeks and the 30 day follow-up period ]
    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) [ Time Frame: Up to 12 weeks ]
    Safety parameters include clinical laboratory assessments, vital signs, weight, oxygen requirement and 12-lead ECG
  • The evaluation of anti-L-DOS47 antibody over time [ Time Frame: Up to 12 weeks ]
    Serum samples will be collected and analyzed from all patients dosed with L-DOS47.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: January 15, 2015)
  • Maximum observed plasma concentration (Cmax) of L-DOS47 at each dose level [ Time Frame: Up to 12 weeks ]
    Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patient dosed with L-DOS47.
  • Time to maximum observed plasma concentration (Tmax) of L-DOS47 at each dose level [ Time Frame: Up to 12 weeks ]
    Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patient dosed with L-DOS47.
  • Area under the concentration (AUC) vs time curve of L-DOS47 at each dose level [ Time Frame: Up to 12 weeks ]
    Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patient dosed with L-DOS47.
  • Terminal elimination half-life of L-DOS47 at each dose level [ Time Frame: Up to 12 weeks ]
    Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patient dosed with L-DOS47.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Phase I/II Open-Label, Non-Randomized Dose Escalation Study of Immunoconjugate L-DOS47
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE Drug: L-DOS47
A treatment cycle will be 21 days with patients receiving L-DOS47 on cycle Days 1 and 8.
Study Arms  ICMJE Experimental: L-DOS47
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: Drug: L-DOS47
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 11, 2017)
76
Original Estimated Enrollment  ICMJE
 (submitted: January 15, 2015)
60
Actual Study Completion Date  ICMJE December 20, 2017
Actual Primary Completion Date August 1, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Main Inclusion Criteria:

Patients will be entered in the study only if they meet all of the following criteria:

  1. Male or female aged ≥ 18 years old
  2. Have histologically confirmed non-squamous NSCLC that are:

    1. Chemo naïve Stage IIIb or IV non-squamous NSCLC who are not candidates for chemotherapy or radiotherapy, or who refused standard therapy
    2. 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.)
  3. Have at least a single measurable lesion in accordance with the RECIST v1.1 criteria.
  4. Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
  5. Have a life expectancy of ≥ 3 months
  6. Have adequate bone marrow, renal and liver function

Main Exclusion Criteria:

  1. Are pregnant or nursing mother
  2. Have a prior history of other malignancies with the exception of non melanoma skin cancer
  3. Have known history of central nervous system (CNS) metastatic disease (previously treated or untreated)
  4. Show evidence of active infection
  5. 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
  6. Have a serious uncontrolled medical condition
  7. Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen, or hepatitis C positive
  8. 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)
  9. Pre-existing peripheral neuropathy ≥ CTC Grade 2
  10. 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
  11. 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.)
  12. Are taking systemic steroids (other than inhalers or topical steroids) or other medication to suppress the immune system
  13. Are participating (or planning to participate) in any other clinical trial during this study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Poland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02340208
Other Study ID Numbers  ICMJE LDOS002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Helix BioPharma Corporation
Study Sponsor  ICMJE Helix BioPharma Corporation
Collaborators  ICMJE Pharm-Olam International
Investigators  ICMJE
Principal Investigator: Dariusz Kowalski, MD, PhD The Maria Sklodowska-Curie Memorial Cancer Centre & Institute of Oncology
PRS Account Helix BioPharma Corporation
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP