Clinical Trials /

PBF-1129 in Patients With NSCLC

NCT03274479

Description:

Phase I clinical trial in Eastern Cooperative Oncology Group (ECOG) 0-1 patients with locally advanced or metastatic NSCLC to evaluate safety and tolerability of the compound PBF-1129, an Adenosine A2b receptor antagonist. The phase I dose escalation will be conducted 3+3 method. Pharmacokinetic (PK) data will be also obtained.

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: PBF-1129 in Patients With NSCLC
  • Official Title: Phase I Trial of PBF-1129 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: PBF-1129CT_03
  • NCT ID: NCT03274479

Conditions

  • Locally Advanced or Metastatic NSCLC

Interventions

DrugSynonymsArms
PBF-1129PBF-1129_40mg

Purpose

Phase I clinical trial in Eastern Cooperative Oncology Group (ECOG) 0-1 patients with locally advanced or metastatic NSCLC to evaluate safety and tolerability of the compound PBF-1129, an Adenosine A2b receptor antagonist. The phase I dose escalation will be conducted 3+3 method. Pharmacokinetic (PK) data will be also obtained.

Trial Arms

NameTypeDescriptionInterventions
PBF-1129_40mgExperimental
  • PBF-1129
PBF-1129_80mgExperimental
  • PBF-1129
PBF-1129_160mgExperimental
  • PBF-1129
PBF-1129_320mgExperimental
  • PBF-1129

Eligibility Criteria

        Inclusion Criteria:

          -  Histological or cytological diagnosis of metastatic squamous or non-squamous NSCLC.

          -  Life expectancy greater or equal to 3 months, as determined by the investigator
             -Patients must have progressed on the standard therapy, including platinum based -
             chemotherapy. Patients with epidermal growth factor receptor (EGFR), anaplastic
             lymphoma kinase (ALK), or ROS-1 mutations must have progressed on standard treatment
             options including EGFR, ALK, or ROS-1-directed therapies.

          -  No limits to the prior lines of treatment

          -  ECOG performance status of 0/1

          -  Measurable Disease by RECIST v1.1

          -  Age greater than 18 years.

          -  Adequate bone marrow, renal and hepatic function:

               -  Absolute neutrophil count (ANC) ≥ 1500 /µL

          -  White blood cell count (WBC) t ≥ 2.5 x 109/L (2500/µL)

               -  Lymphocyte count ≥ 0.5 x 109/L (500/µL)

          -  Platelet count ≥ 100 x 109/L (100,000/µL) without transfusion

          -  Hemoglobin ≥ (9.0 g/dL) - patients may be transfused to meet this criterion.

          -  Aspartate aminotransferase AST, alanine aminotransferase (ALT), and alkaline
             phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN)

               -  Serum bilirubin ≤ 1.5 x ULN, with the exception of patients with known Gilbert
                  disease: serum bilirubin level ≤ 3 x ULN

               -  Creatinine clearance >60 mL/min (calculated using the Cockcroft-Gault formula) or
                  by 24-hours urine collection

          -  Written informed consent and any locally-required authorization obtained from the
             subject prior to performing any protocol-related procedures, including screening
             evaluations

          -  Subject is willing and able to comply with the protocol for the duration of the study

        Exclusion Criteria:

          -  Participation in another clinical study with an investigational product during the
             last 4 weeks or 5 half-lives prior to starting on treatment.

          -  Symptomatic and/or untreated or actively progressing central nervous system (CNS)
             metastases or leptomeningeal disease. Patients with a history of treated CNS
             metastases are eligible, provided that all of the following criteria are met:

               -  The patient has not received stereotactic radiotherapy within 7 days prior to
                  initiation of study treatment or whole-brain radiotherapy within 14 days prior to
                  initiation of study treatment.

               -  The patient has no ongoing requirement for corticosteroids as therapy for CNS
                  disease. Anti-convulsant therapy at a stable dose is permitted.

          -  Serious uncontrolled medical disorder or active infection that would impair the
             patient's ability to receive study treatment.

          -  Concurrent use of other anticancer approved or investigational agents is not allowed.

          -  Autoimmune disorder

          -  Prior malignancy in past 2 years or as identified in Section 7.2 of this protocol

          -  Active or prior documented autoimmune disease within the past 2 years. NOTE: Patients
             with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within
             the past 2 years) are not excluded.

          -  Patients receiving systemic steroids ≥ 10mg/day of prednisone or the equivalent

          -  Smoking (cigarettes, cigars or pipes) must be discontinued at least 7 days prior to
             initiating study drug administration; smoking cessation products (transdermal nicotine
             patches or chewing gum may be used.

          -  Pregnancy or breastfeeding, or intention of becoming pregnant during the study. Female
             subjects must either be of non-reproductive potential or have a negative serum
             pregnancy test result within 14 days prior to initiation of study treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) of PBF-1129
Time Frame:28 days
Safety Issue:
Description:The MTD evaluation will be based on the Dose-limiting Toxicity (DLT) of the treated Population, which includes all subjects who receive any dose of PBF-1129, and will include Adverse events (AEs), Serious Adverse events (SAEs), laboratory evaluations and electrocardiogram (ECG) results

Secondary Outcome Measures

Measure:Time to PBF-1129 peak concentration in plasma "Tmax"
Time Frame:days 1 and 29
Safety Issue:
Description:The parameter will be calculated from plasma samples collected at days 1 and 29 after drug administration.It will consist in the time (in minutes) to reach the maximum "PBF-1129" concentration in plasma samples of patients after oral administration of PBF-1129.
Measure:Time to PBF-1129 peak concentration in plasma at steady state "Tmax,ss"
Time Frame:days 1 and 29
Safety Issue:
Description:The parameter will be calculated from plasma samples collected at days 1 and 29 after drug administration. It will consist in the time (in minutes) to reach the maximum "PBF-1129" concentration in plasma samples of patients during a dosing interval at steady state.
Measure:PBF-1129 peak concentration in plasma "Cmax"
Time Frame:days 1 and 29
Safety Issue:
Description:The parameter will be calculated from plasma samples collected at days 1 and 29 after drug administration. It will consist in the maximum plasma concentration (ng/mL) of PBF-1129 observed after administration.
Measure:PBF-1129 peak concentration in plasma at steady state"Cmax,ss"
Time Frame:days 1 and 29
Safety Issue:
Description:The parameter will be calculated from plasma samples collected at days 1 and 29 after drug administration.It will consist in the maximum plasma concentration (ng/mL) of PBF-1129 observed during a dosing interval at steady state.
Measure:The area under PBF-1129 plasma concentration-time curve to infinite time "AUC(0-inf)"
Time Frame:days 1 and 29
Safety Issue:
Description:The parameter will be calculated from plasma samples collected at days 1 and 29 after drug administration. It will consist in the area under the concentration-time curve from zero up to ∞ with extrapolation of the terminal phase. "AUC(0-inf)" will be given in Amount·time/ volume units
Measure:The area under PBF-1129 plasma concentration-time curve up to time 't' "AUC(0-t)"
Time Frame:days 1 and 29
Safety Issue:
Description:The parameter will be calculated from plasma samples collected at days 1 and 29 after drug administration.It will consist in the area under the concentration-time curve from zero up to a definite time t. "AUC(0-t)" will be given in Amount·time/ volume units.
Measure:The area under PBF-1129 plasma concentration-time curve over the dosing interval "AUC(0-τ)"
Time Frame:days 1 and 29
Safety Issue:
Description:The parameter will be calculated from plasma samples collected at days 1 and 29 after drug administration. It will consist in the area under the concentration-time curve over the dosing interval. "AUC(0-τ)" will be given in Amount·time/ volume units.
Measure:PBF-1129 half-life in plasma " t½"
Time Frame:days 1 and 29
Safety Issue:
Description:The parameter will be calculated from plasma samples collected at days 1 and 29 after drug administration. It will consist in the terminal half-life of PBF-1129 in plasma. "t½" will be given in hours (h)
Measure:Efficacy as measured by Objective response rate (ORR)
Time Frame:2 years
Safety Issue:
Description:ORR: Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).ORR is defined as confirmed complete response (CR) or partial response (PR) based on modified RECIST v1.1.
Measure:Efficacy as measured by Disease control rate (DCR)
Time Frame:2 years
Safety Issue:
Description:The disease control rate (DCR) will be estimated considering the following variables: Complete response (CR), Partial response (PR) and stable disease (SD) as described by Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). These variables will be assessed based on Imaging-based evaluation methods as chest x-ray, conventional computed tomography (CT) and magnetic resonance imaging (MRI) that will be performed every 2 cycles of 28 days administration.
Measure:Efficacy as measured by duration of response (DoR)
Time Frame:2 years
Safety Issue:
Description:Duration of response (DoR) is defined as the duration from the first documentation of OR to the first documented disease progression or death due to any cause, whichever occurs first
Measure:Efficacy as measured by progression-free survival (PFS)
Time Frame:2 years
Safety Issue:
Description:Progression-free survival (PFS) will be measured from the start of treatment until the documentation of disease progression or death due to any cause, whichever occurs first. For subjects who are alive and progression-free at the time of data cut-off for analysis, PFS will be censored at the last tumor assessment date.
Measure:Efficacy as measured by overall survival (OS)
Time Frame:2 years
Safety Issue:
Description:Overall survival (OS) will be determined as the time from the start of treatment until death due to any cause.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Palobiofarma SL

Trial Keywords

  • adenosine receptors
  • checkpoint inhibitors
  • immune system activator

Last Updated

November 5, 2018