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

Primary Purpose

Non-Small Cell Lung Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
L-DOS47
Sponsored by
Helix BioPharma Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

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

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Hospitals Case Medical Center
  • The University of Texas MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pemetrexed and Carboplatin plus L-DOS47

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of patients with adverse events as a measure safety and tolerability of L-DOS47 in combination treatment with pemetrexed/carboplatin
The AE reporting period starts on Cycle 1 Day 1 up to the last study visit.

Secondary Outcome Measures

Objective response rate of patients receiving the combination treatment according to RECIST 1.1
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
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
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
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
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
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
Serum samples will be collected and analyzed from all patients dosed with L-DOS47

Full Information

First Posted
April 9, 2013
Last Updated
February 20, 2020
Sponsor
Helix BioPharma Corporation
Collaborators
Theradex
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1. Study Identification

Unique Protocol Identification Number
NCT02309892
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
April 2014 (undefined)
Primary Completion Date
August 2019 (Actual)
Study Completion Date
September 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Helix BioPharma Corporation
Collaborators
Theradex

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 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.

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
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pemetrexed and Carboplatin plus L-DOS47
Arm Type
Experimental
Arm Description
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 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, 8, and 15 and pemetrexed/carboplatin on Day 1 of each treatment cycle.
Primary Outcome Measure Information:
Title
Number of patients with adverse events as a measure safety and tolerability of L-DOS47 in combination treatment with pemetrexed/carboplatin
Description
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
Secondary Outcome Measure Information:
Title
Objective response rate of patients receiving the combination treatment according to RECIST 1.1
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.
Time Frame
Up to 12 weeks
Title
Number of patient receiving a sustained clinical benefit
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.
Time Frame
Up to 12 weeks
Title
Maximum observed plasma concentration (Cmax) of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin
Description
Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47
Time Frame
Up to 12 weeks
Title
Time to maximum observed plasma concentration (Tmax) of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin
Description
Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47
Time Frame
Up to 12 weeks
Title
Area under the concentration (AUC) vs time curve of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin
Description
Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47
Time Frame
Up to 12 weeks
Title
Terminal elimination half-life of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin
Description
Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47
Time Frame
Up to 12 weeks
Title
The presence of anti-L-DOS47 antibodies for patients dosed with L-DOS47 in combination treatment with pemetrexed/carboplatin
Description
Serum samples will be collected and analyzed from all patients 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: Male or female patient ≥ 18 years of age Histologically or cytologically confirmed non-squamous NSCLC EGFR-mutation positive patients must have progressed on or had intolerance to an EGFR small molecule tyrosine kinase inhibitor Patients whose tumors harbor an anaplastic lymphoma kinase (ALK) translocation must have progressed on or had intolerance to an ALK inhibitor; No prior adjuvant chemotherapy within 1 year of the first treatment day if there is recurrent disease At least 1 site of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and minimum life expectancy of ≥ 3 months Adequate bone marrow, renal and liver function Main Exclusion Criteria: Histologic evidence of predominantly squamous cell NSCLC Brain metastasis and/or leptomeningeal disease (known or suspected) Peripheral neuropathy > CTCAE grade 1 Possibility of a curative local treatment (surgery and/or radiotherapy) Previous chemotherapy except adjuvant treatment with progression of disease documented ≥ 12 months after end of adjuvant treatment 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 Concurrent chronic systemic immunotherapy, chemotherapy or hormone therapy
Facility Information:
Facility Name
University Hospitals Case Medical Center
City
Cleveland
State/Province
Ohio
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.helixbiopharma.com
Description
Helix BioPharma corporate website

Learn more about this trial

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

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