Study of ADI-PEG 20 in Patients With Relapsed Sensitive or Refractory Small Cell Lung Cancer
Condition: Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: ADI-PEG 20 (Arginine deiminase pegylated)
Intervention description: 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)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: small cell lung cancer; SCLC; ADI-PEG 20; arginine deiminase pegylated

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.
    

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