Clinical trial NCT03274479: PBF-1129 in Patients With NSCLC
Official title: Phase I Trial of PBF-1129 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Locally Advanced or Metastatic NSCLC
Keywords: adenosine receptors
checkpoint inhibitors
immune system activator
Lead sponsor: Palobiofarma SL
Sponsor class: INDUSTRY
Collaborators: name: Ohio State University
First posted: 2017-09-07
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of PBF-1129
timeFrame: 28 days
Secondary outcomes:
measure: Time to PBF-1129 peak concentration in plasma "Tmax"
timeFrame: days 1 and 29
measure: Time to PBF-1129 peak concentration in plasma at steady state "Tmax,ss"
timeFrame: days 1 and 29
measure: PBF-1129 peak concentration in plasma "Cmax"
timeFrame: days 1 and 29
measure: PBF-1129 peak concentration in plasma at steady state"Cmax,ss"
timeFrame: days 1 and 29
measure: The area under PBF-1129 plasma concentration-time curve to infinite time "AUC(0-inf)"
timeFrame: days 1 and 29
measure: The area under PBF-1129 plasma concentration-time curve up to time 't' "AUC(0-t)"
timeFrame: days 1 and 29
measure: The area under PBF-1129 plasma concentration-time curve over the dosing interval "AUC(0-τ)"
timeFrame: days 1 and 29
measure: PBF-1129 half-life in plasma " t½"
timeFrame: days 1 and 29
measure: Efficacy as measured by Objective response rate (ORR)
timeFrame: 2 years
measure: Efficacy as measured by Disease control rate (DCR)
timeFrame: 2 years
measure: Efficacy as measured by duration of response (DoR)
timeFrame: 2 years
measure: Efficacy as measured by progression-free survival (PFS)
timeFrame: 2 years
measure: Efficacy as measured by overall survival (OS)
timeFrame: 2 years
Other outcomes:
Locations:
city: Ohio City
country: United States
facility: Division of medical Oncology A450B Starling Loving Hall
state: Ohio
Study officials:
References: