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A Dose Escalation Study of L-DOS47 in Recurrent or Metastatic Non-Squamous NSCLC

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ClinicalTrials.gov Identifier: NCT02309892
Recruitment Status : Completed
First Posted : December 5, 2014
Last Update Posted : February 24, 2020
Sponsor:
Collaborator:
Theradex
Information provided by (Responsible Party):
Helix BioPharma Corporation

Tracking Information
First Submitted Date  ICMJE April 9, 2013
First Posted Date  ICMJE December 5, 2014
Last Update Posted Date February 24, 2020
Study Start Date  ICMJE April 2014
Actual Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 3, 2014)
Number of patients with adverse events as a measure safety and tolerability of L-DOS47 in combination treatment with pemetrexed/carboplatin [ Time Frame: Participants will be followed for 12 weeks ]
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: December 3, 2014)
  • Objective response rate of patients receiving the combination treatment according to RECIST 1.1 [ Time Frame: Up to 12 weeks ]
    Objective tumor response will be assessed according to RECIST version 1.1 in patients who have completed at least 2 cycles of study treatment and who have at least 1 post-treatment disease assessment.
  • Number of patient receiving a sustained clinical benefit [ Time Frame: Up to 12 weeks ]
    Defined as the percentage of patients who have achieved complete response, partial response, and stable disease following combination treatment with L-DOS47 + pemetrexed/carboplatin.
  • Maximum observed plasma concentration (Cmax) of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin [ Time Frame: Up to 12 weeks ]
    Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47
  • Time to maximum observed plasma concentration (Tmax) of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin [ Time Frame: Up to 12 weeks ]
    Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47
  • Area under the concentration (AUC) vs time curve of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin [ Time Frame: Up to 12 weeks ]
    Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47
  • Terminal elimination half-life of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin [ Time Frame: Up to 12 weeks ]
    Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47
  • The presence of anti-L-DOS47 antibodies for patients dosed with L-DOS47 in combination treatment with pemetrexed/carboplatin [ 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 Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Dose Escalation Study of L-DOS47 in Recurrent or Metastatic Non-Squamous NSCLC
Official Title  ICMJE A Phase I, Open Label, Dose Escalation Study of Immunoconjugate L-DOS47 in Combination With Pemetrexed/Carboplatin in Patients With Stage IV (TNM M1a and M1b) Recurrent or Metastatic NSCL Lung Cancer
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 combination with standard doublet therapy of pemetrexed/carboplatin in patients with Stage IV (TNM M1a and M1b) recurrent or metastatic non-squamous Non-Small Cell Lung Cancer.
Detailed Description It is planned that patients will receive 4 cycles of combination treatment with L-DOS47 + pemetrexed/carboplatin. Patients who have not progressed following the 4 cycles of combination treatment and who have not experienced unacceptable toxicity will have the opportunity to continue to receive L-DOS47 treatment for as long as there is clinical benefit and it is well-tolerated, in the opinion of the Investigator, until disease progression. Patients who are unable to complete 4 cycles of L-DOS47 + pemetrexed/carboplatin combination treatment due to pemetrexed/carboplatin toxicity will have the opportunity to continue receiving L-DOS47 treatment following discontinuation of pemetrexed/carboplatin, for as long as there is clinical benefit and it is well-tolerated, in the opinion of the Investigator, until disease progression.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
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, 8, and 15 and pemetrexed/carboplatin on Day 1 of each treatment cycle.
Study Arms  ICMJE Experimental: Pemetrexed and Carboplatin plus L-DOS47
Patients 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 0.59 µg/kg; further possible dose levels that may be assessed are 0.78, 1.04, 1.38 and 1.84 µg/kg. The standard of care doses of pemetrexed [500 mg/m2] and carboplatin [AUC6], respectively, to be administered in combination with L-DOS47, will remain constant across cohorts.
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: February 20, 2020)
14
Original Estimated Enrollment  ICMJE
 (submitted: December 3, 2014)
40
Actual Study Completion Date  ICMJE September 2019
Actual Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Main Inclusion Criteria:

  1. Male or female patient ≥ 18 years of age
  2. Histologically or cytologically confirmed non-squamous NSCLC
  3. EGFR-mutation positive patients must have progressed on or had intolerance to an EGFR small molecule tyrosine kinase inhibitor
  4. Patients whose tumors harbor an anaplastic lymphoma kinase (ALK) translocation must have progressed on or had intolerance to an ALK inhibitor;
  5. No prior adjuvant chemotherapy within 1 year of the first treatment day if there is recurrent disease
  6. At least 1 site of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and minimum life expectancy of ≥ 3 months
  8. Adequate bone marrow, renal and liver function

Main Exclusion Criteria:

  1. Histologic evidence of predominantly squamous cell NSCLC
  2. Brain metastasis and/or leptomeningeal disease (known or suspected)
  3. Peripheral neuropathy > CTCAE grade 1
  4. Possibility of a curative local treatment (surgery and/or radiotherapy)
  5. Previous chemotherapy except adjuvant treatment with progression of disease documented ≥ 12 months after end of adjuvant treatment
  6. Having received treatment in another clinical study within the 30 days prior to commencing study treatment or having side effects of a prior study drug that are not recovered to grade ≤ 1 or baseline, except for alopecia
  7. Concurrent chronic systemic immunotherapy, chemotherapy or hormone therapy
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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02309892
Other Study ID Numbers  ICMJE LDOS001
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 Theradex
Investigators  ICMJE Not Provided
PRS Account Helix BioPharma Corporation
Verification Date February 2020

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