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Trial record 1 of 1 for:    ADI-PEG 20, small cell
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Study of ADI-PEG 20 in Patients With Relapsed Sensitive or Refractory Small Cell Lung Cancer

This study has been terminated.
(Lack of efficacy in Cohort 2; slow enrollment in Cohort 1)
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
ClinicalTrials.gov Identifier:
NCT01266018
First received: December 22, 2010
Last updated: May 10, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention Phase
Small Cell Lung Cancer Drug: ADI-PEG 20 (Arginine deiminase pegylated) Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of ADI-PEG 20 in Patients With Relapsed Sensitive or Refractory Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Ludwig Institute for Cancer Research:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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.


Enrollment: 22
Study Start Date: January 2011
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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 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.
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

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01266018

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Belgium
University Clinic Saint-Luc
Brussels, Belgium, B-1200
Germany
Krankenhaus Nordwest
Frankfurt, Germany, D-60488
Taiwan
National Cheng Kung University Hospital
Tainan City, Taiwan, 704
National Taiwan University Hospital
Taipei City, Taiwan, 10002
Chang Gung Memorial Hospital - LinKou Branch
Taoyuan, Taiwan, 333
United Kingdom
St. Bartholomew's Hospital
West Smithfield, London, United Kingdom, EC1A 7BE
Sponsors and Collaborators
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
Investigators
Study Chair: Lee M Krug, MD Memorial Sloan Kettering Cancer Center
  More Information

Responsible Party: Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier: NCT01266018     History of Changes
Other Study ID Numbers: LUD2009-007
Pro00022622 ( Other Identifier: Duke University Medical Center )
Study First Received: December 22, 2010
Results First Received: November 30, 2016
Last Updated: May 10, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Keywords provided by Ludwig Institute for Cancer Research:
small cell lung cancer
SCLC
ADI-PEG 20
arginine deiminase pegylated

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms

ClinicalTrials.gov processed this record on August 21, 2017