Clinical trial NCT02309892: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Cancer
Neoplasms
Immunoconjugate
Tumor microenvironment alkalinization
Lead sponsor: Helix BioPharma Corporation
Sponsor class: INDUSTRY
Collaborators: name: Theradex
First posted: 2014-12-05
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Single arm, dose escalation where patients are recruited into cohorts of escalating doses of L-DOS47 (0.59 up to 12.0 µg/kg) in combination with pemetrexed and carboplatin.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin
timeFrame: Up to 12 weeks
measure: Number of Participants With Dose Limited Toxicities (DLTs) Related to L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin.
timeFrame: Up to 21 days
measure: Maximum Tolerated Dose of L-DOS47 in Combination With Pemetrexed/Carboplatin
timeFrame: 21 days
Secondary outcomes:
measure: Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1
timeFrame: Up to 12 weeks
measure: Percentage of Patients Receiving a Sustained Clinical Benefit
timeFrame: Up to 12 weeks
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
References: