Clinical trial NCT01266018: Study of ADI-PEG 20 in Patients With Relapsed Sensitive or Refractory Small Cell Lung Cancer
Official title: Phase II Study of ADI-PEG 20 in Patients With Relapsed Sensitive or Refractory Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Small Cell Lung Cancer
Keywords: small cell lung cancer
SCLC
ADI-PEG 20
arginine deiminase pegylated
Lead sponsor: Ludwig Institute for Cancer Research
Sponsor class: OTHER
Collaborators: name: Memorial Sloan Kettering Cancer Center
name: Duke University
name: St. Bartholomew's Hospital
name: Krankenhaus Nordwest
name: Saint-Luc University Hospital
name: National Taiwan University Hospital
name: National Cheng-Kung University Hospital
name: Chang Gung Memorial Hospital
name: Austin Health
name: Polaris Group
First posted: 2010-12-24
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This was a 2-arm, open-label, phase 2 study of pegylated arginine deiminase (ADI-PEG) 20 in subjects with relapsed sensitive or refractory small cell lung cancer (SCLC). ADI-PEG 20 was administered intramuscularly (IM) at a fixed dose of 320 IU/m\^2 once weekly for a 4-week cycle. The primary objective was to assess clinical efficacy with a primary endpoint of tumor response by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 after 4 weeks. Secondary objectives were to assess the safety, pharmacodynamics, and immunogenicity of ADI-PEG 20, as well as clinical efficacy with a secondary endpoint of overall survival.

Detailed description: Subjects were enrolled sequentially (non-randomized) into two separate cohorts in parallel. Cohort 1 comprised subjects with "sensitive" disease and Cohort 2 comprised subjects with "refractory" disease. Both cohorts received the same treatment regimen consisting of 4 weekly IM administrations of ADI-PEG 20 (320 IU/m\^2), followed by a 1-week follow-up (1 cycle). No dose adjustment was allowed. Additional treatment cycles were permitted in the absence of disease progression requiring other therapeutic interventions.

Each cohort was to be enrolled in 2 stages. In the first stage, 15 subjects were to be accrued in Cohort 1 and 12 subjects in Cohort 2. If ≥ 3 subjects met the primary endpoint in Cohort 1, then an additional 13 subjects were to be accrued in the second stage. If ≤ 2 subjects met the primary endpoint in Cohort 1, then the study was to be terminated and declared negative for Cohort 1. If ≥ 1 subject met the primary endpoint in Cohort 2, then an additional 4 subjects were to be accrued in the second stage. If no subjects met the primary endpoint in Cohort 2, then the study was to be terminated and declared negative. Additionally, if at any time a death or two grade 4 adverse events (AEs) that were definitely related or probably related to the study drug occurred, then the study was to be stopped.

Eligibility criteria: Inclusion Criteria:

1. Subjects must have had histologically documented SCLC
2. Assigned to one of two cohorts based on the following characteristics: Cohort 1: "Sensitive" disease subjects who had 1 previous line of chemotherapy and maintained an appropriate response for 90 days or more; or Cohort 2: "Refractory" disease subjects, who had (a) 1 previous line of chemotherapy and either had no response or progressed in less than 90 days after completing treatment or (b) any subject ("sensitive" or "refractory") in need of third-line therapy, i.e., who completed or failed 2 previous lines of chemotherapy
3. Measurable disease using RECIST version 1.1
4. Argininosuccinate synthetase (ASS) tumor expression was either negative or \< 5% + tumor cells by immunohistochemistry analysis
5. Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2
6. Laboratory parameters for vital functions in the normal range. Laboratory abnormalities that were not clinically significant were generally permitted, except for the following laboratory parameters, which were to be within the ranges specified:

   * Neutrophil count: ≥ 1.5 x 10\^9/L
   * Lymphocyte count: ≥ 0.5 x 10\^9/L
   * Platelet count: ≥ 50 x 10\^9/L
   * Serum creatinine: ≤ 1.5 x upper limit of normal (ULN) (or creatinine clearance ≥ 60 mL/min)
   * Serum bilirubin: ≤ 2 mg/dL (or ≤ 34 µmol/L)
   * Serum uric acid: ≤ 8 mg/dL (or ≤ 0.48 mmol/L)
   * International normalized ratio (INR): ≤ 1.5
   * Partial thromboplastin time: ≤ 1.5 x ULN
7. Age ≥ 18 years
8. Able and willing to give valid written informed consent

Exclusion Criteria:

1. Previous treatment with ADI-PEG 20
2. Known allergy to pegylated products
3. History of uncontrolled seizures
4. Serious illnesses, e.g., serious infections requiring antibiotics, bleeding disorders, or any condition that in the opinion of the Investigator would interfere with the ability of the patient to fulfill the study requirements
5. Metastatic disease to the central nervous system, unless treated and stable
6. Known immunodeficiency or human immunodeficiency virus (HIV) positivity
7. Participation in another clinical trial involving another investigational agent within 3 weeks prior to first dosing of study agent
8. Any other malignancy that required protocol-specified restricted concomitant therapy
9. Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study
10. Lack of availability for clinical follow-up assessment
11. Pregnancy or breast feeding
12. Refusal or inability to use effective means of contraception for men and women of childbearing potential for the duration of the study

Primary outcomes:
measure: Best Overall Response
timeFrame: Every 4 to 8 weeks for up to 16 weeks
Secondary outcomes:
measure: Assessment of Safety of Arginine Deiminase Pegylated (ADI-PEG) 20
timeFrame: Every 1 to 4 weeks for up to 16 weeks
measure: Assessment of Pharmacodynamics of ADI-PEG 20
timeFrame: Every 1 to 4 weeks for up to 16 weeks
measure: Assessment of Immunogenicity of ADI-PEG 20
timeFrame: Every 1 to 4 weeks for up to 16 weeks
measure: Assessment of Overall Survival
timeFrame: Every 4 weeks for up to 16 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Brussels
country: Belgium
facility: University Clinic Saint-Luc
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest
city: Tainan City
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital - LinKou Branch
city: West Smithfield
country: United Kingdom
facility: St. Bartholomew's Hospital
state: London
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Lee M Krug, MD
role: STUDY_CHAIR
References: