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

• Status: Terminated
• Trial end date: 2014-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ludwig Institute for Cancer Research
• Collaborators: Austin Health; Chang Gung Memorial Hospital; Duke University; Krakenhaus Nordwest; Krankenhaus Nordwest; Memorial Sloan Kettering Cancer Center; National Cheng-Kung University Hospital; National ChengKung University Hospital; National Taiwan University Hospital; Polaris Group; Saint-Luc University Hospital; St. Bartholomew's Hospital; St. Luc Hospital

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