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

Phase 1TerminatedNCT02309892

Helix BioPharma Corporation14 enrolled

Overview

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.

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

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Non-Small Cell Lung Cancer

Interventions

L-DOS47DRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (2)

University Hospitals Case Medical Center

Cleveland, Ohio, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Outcomes

Primary Outcomes

Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin

Beginning with the start of study treatment at Cycle 1 Day 1 up to the last study visit: An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose which results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or, is a congenital anomaly/birth defect. Beginning with the AE reporting period at the start of study treatment at Cycle 1 Day 1 up to the last study visit;

Time frame: Up to 12 weeks

Number of Participants With Dose Limited Toxicities (DLTs) Related to L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin.

A DLT was defined as the occurrence of any of the following events (according to NCI CTCAE version 4.0) that are considered to be (possibly/probably/definitely) related to L-DOS47 and occurring within 21 days after commencing study treatment: * Haematological adverse events ≥ grade 4 * Non-haematological adverse events ≥ grade 3 * One instance each of any two unique grade 2 adverse events

Time frame: Up to 21 days

Maximum Tolerated Dose of L-DOS47 in Combination With Pemetrexed/Carboplatin

Defined as the highest dose level at which ≤ 1 of 6 patients experiences a dose limiting toxicity (DLT) as assessed during the first treatment cycle. If no DLT are reported, it is assumed that the maximum tolerated dose of L-DOS47 in combination with pemetrexed/carboplatin was not reached.

Time frame: 21 days

Secondary Outcomes

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; where complete response (CR) is the disappearance of all target lesions and partial response (PR) is at least a 30% reduction in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.