Clinical Trials /

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

NCT02309892

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Dose Escalation Study of L-DOS47 in Recurrent or Metastatic Non-Squamous NSCLC
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: LDOS001
  • NCT ID: NCT02309892

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
L-DOS47Pemetrexed and Carboplatin plus L-DOS47

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Pemetrexed and Carboplatin plus L-DOS47ExperimentalPatients 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.
  • L-DOS47

Eligibility Criteria

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

Primary Outcome Measures

Measure: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
Safety Issue:
Description:The AE reporting period starts on Cycle 1 Day 1 up to the last study visit.

Secondary Outcome Measures

Measure:Objective response rate of patients receiving the combination treatment according to RECIST 1.1
Time Frame:Up to 12 weeks
Safety Issue:
Description: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.
Measure:Number of patient receiving a sustained clinical benefit
Time Frame:Up to 12 weeks
Safety Issue:
Description:Defined as the percentage of patients who have achieved complete response, partial response, and stable disease following combination treatment with L-DOS47 + pemetrexed/carboplatin.
Measure:Maximum observed plasma concentration (Cmax) of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin
Time Frame:Up to 12 weeks
Safety Issue:
Description:Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47
Measure:Time to maximum observed plasma concentration (Tmax) of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin
Time Frame:Up to 12 weeks
Safety Issue:
Description:Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47
Measure: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
Safety Issue:
Description:Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47
Measure:Terminal elimination half-life of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin
Time Frame:Up to 12 weeks
Safety Issue:
Description:Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47
Measure: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
Safety Issue:
Description:Serum samples will be collected and analyzed from all patients dosed with L-DOS47

Details

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

Trial Keywords

  • Non-Small Cell Lung Cancer
  • Neoplasms
  • Immunoconjugate
  • Tumor microenvironment alkalinization

Last Updated