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Study of ADI-PEG 20 in Patients With Relapsed Sensitive or Refractory Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT01266018
Recruitment Status : Terminated (Lack of efficacy in Cohort 2; slow enrollment in Cohort 1)
First Posted : December 24, 2010
Results First Posted : June 6, 2017
Last Update Posted : June 6, 2017
Sponsor:
Collaborators:
Memorial Sloan Kettering Cancer Center
Duke University
St. Bartholomew's Hospital
Krankenhaus Nordwest
Saint-Luc University Hospital
National Taiwan University Hospital
National Cheng-Kung University Hospital
Chang Gung Memorial Hospital
Austin Health
Polaris Group
Information provided by (Responsible Party):
Ludwig Institute for Cancer Research

December 22, 2010
December 24, 2010
November 30, 2016
June 6, 2017
June 6, 2017
January 2011
January 2014   (Final data collection date for primary outcome measure)
Best Overall Response [ Time Frame: Every 4 to 8 weeks for up to 16 weeks ]

Tumor responses were evaluated using any appropriate imaging type and were categorized according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Per RECIST for target lesions and assessed by MRI:

Complete Response (CR): Disappearance of all target lesions [no evidence of disease]; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.

Assessment of clinical efficacy of tumor response by RECIST after 4 weeks [ Time Frame: Every 4 weeks ]
Complete list of historical versions of study NCT01266018 on ClinicalTrials.gov Archive Site
  • Assessment of Safety of Arginine Deiminase Pegylated (ADI-PEG) 20 [ Time Frame: Every 1 to 4 weeks for up to 16 weeks ]
    Analysis of treatment-emergent adverse events (TEAEs) reported from clinical laboratory tests, physical examinations, and vital signs.
  • Assessment of Pharmacodynamics of ADI-PEG 20 [ Time Frame: Every 1 to 4 weeks for up to 16 weeks ]
    Blood samples were collected from all subjects at enrollment, prior to each treatment, and at the end of study to evaluate changes in plasma arginine and citrulline levels following administration of ADI-PEG 20. Disease state (ie, relapsed sensitive vs refractory) was not considered relevant to this analysis and as such samples were collected without regard for cohort assignment.
  • Assessment of Immunogenicity of ADI-PEG 20 [ Time Frame: Every 1 to 4 weeks for up to 16 weeks ]
    Blood samples were collected for all subjects at enrollment, prior to each treatment, and at the end of study to evaluate changes in ADI-PEG 20 antibody titer in peripheral blood over time. Disease state (ie, relapsed sensitive vs refractory) was not considered relevant to this analysis and as such samples were collected without regard for cohort assignment.
  • Assessment of Overall Survival [ Time Frame: Every 4 weeks for up to 16 months ]
    Overall survival was measured from the initial date of treatment to the recorded date of death. Because the study was terminated prematurely, no statistical analyses of overall survival data were performed.
  • 1. Assessment of safety of ADI-PEG 20 [ Time Frame: Every 4 weeks ]
  • 2. Assessment of pharmacodynamics of ADI-PEG 20 [ Time Frame: Every 4 weeks ]
  • 3. Assessment of immunogenicity of ADI-PEG 20 [ Time Frame: Every 4 weeks ]
  • 4. Assessment of overall survival. [ Time Frame: Every 4 weeks ]
Not Provided
Not Provided
 
Study of ADI-PEG 20 in Patients With Relapsed Sensitive or Refractory Small Cell Lung Cancer
Phase II Study of ADI-PEG 20 in Patients With Relapsed Sensitive or Refractory Small Cell Lung Cancer
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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Small Cell Lung Cancer
Drug: ADI-PEG 20 (Arginine deiminase pegylated)
ADI-PEG 20 was administered intramuscularly (IM) at a fixed dose of 320 IU/m^2 (36.8 mg/m^2) once weekly for 4 weeks followed by a 1-week follow-up (1 cycle)
Other Names:
  • ADI
  • Arginine deiminase pegylated
  • Experimental: Cohort 1: Sensitive Disease
    Cohort 1 comprised subjects with "sensitive" disease, defined as subjects who were treated with 1 previous line of chemotherapy and maintained an appropriate response for 90 days or more. Subjects received 4 administrations of ADI-PEG 20 (320 IU/m^2) followed by 1 week of follow-up in each treatment cycle.
    Intervention: Drug: ADI-PEG 20 (Arginine deiminase pegylated)
  • Experimental: Cohort 2: Refractory Disease
    Cohort 2 comprised subjects with "refractory" disease, defined as subjects who either (a) were treated with 1 previous line of chemotherapy and either had no response or progressed < 90 days after completing treatment or (b) required third-line therapy, i.e., had completed 2 previous lines of chemotherapy, regardless of response. Subjects received 4 administrations of ADI-PEG 20 (320 IU/m^2) followed by 1 week of follow-up in each treatment cycle.
    Intervention: Drug: ADI-PEG 20 (Arginine deiminase pegylated)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
22
45
January 2014
January 2014   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Belgium,   Germany,   Taiwan,   United Kingdom,   United States
 
 
NCT01266018
LUD2009-007
Pro00022622 ( Other Identifier: Duke University Medical Center )
No
Not Provided
Plan to Share IPD: Yes
Ludwig Institute for Cancer Research
Ludwig Institute for Cancer Research
  • Memorial Sloan Kettering Cancer Center
  • Duke University
  • St. Bartholomew's Hospital
  • Krankenhaus Nordwest
  • Saint-Luc University Hospital
  • National Taiwan University Hospital
  • National Cheng-Kung University Hospital
  • Chang Gung Memorial Hospital
  • Austin Health
  • Polaris Group
Study Chair: Lee M Krug, MD Memorial Sloan Kettering Cancer Center
Ludwig Institute for Cancer Research
May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP