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

NCT01266018 | Terminated Phase 2 Results

• 2 other identifiers: LUD2009-007Pro00022622
• Study Type: interventional
• Target: 22
• Locations: 5 countries
• Sites: 8

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.

Conditions

Small Cell Lung Cancer

Keywords

small cell lung cancer; SCLC; ADI-PEG 20; arginine deiminase pegylated

Outcome Measures

Primary Outcomes (1)

• Best Overall Response

  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.

  Every 4 to 8 weeks for up to 16 weeks

Secondary Outcomes (4)

• Assessment of Safety of Arginine Deiminase Pegylated (ADI-PEG) 20

  Every 1 to 4 weeks for up to 16 weeks

• Assessment of Pharmacodynamics of ADI-PEG 20

  Every 1 to 4 weeks for up to 16 weeks

• Assessment of Immunogenicity of ADI-PEG 20

  Every 1 to 4 weeks for up to 16 weeks

• Assessment of Overall Survival

  Every 4 weeks for up to 16 months

Study Arms (2)

Cohort 1: Sensitive Disease

EXPERIMENTAL

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)

Cohort 2: Refractory Disease

EXPERIMENTAL

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)

Interventions

ADI-PEG 20 (Arginine deiminase pegylated) DRUG

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)

Also known as: ADI, Arginine deiminase pegylated

Cohort 1: Sensitive Disease; Cohort 2: Refractory Disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have had histologically documented SCLC
• 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
• Measurable disease using RECIST version 1.1
• Argininosuccinate synthetase (ASS) tumor expression was either negative or \< 5% + tumor cells by immunohistochemistry analysis
• Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2
• 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
• Age ≥ 18 years

You may not qualify if:

• Previous treatment with ADI-PEG 20
• Known allergy to pegylated products
• History of uncontrolled seizures
• 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
• Metastatic disease to the central nervous system, unless treated and stable
• Known immunodeficiency or human immunodeficiency virus (HIV) positivity
• Participation in another clinical trial involving another investigational agent within 3 weeks prior to first dosing of study agent
• Any other malignancy that required protocol-specified restricted concomitant therapy
• Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study
• Lack of availability for clinical follow-up assessment
• Pregnancy or breast feeding
• Refusal or inability to use effective means of contraception for men and women of childbearing potential for the duration of the study

Sponsors & Collaborators

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

Study Sites (8)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University Clinic Saint-Luc

Brussels, B-1200, Belgium

Location

Krankenhaus Nordwest

Frankfurt, D-60488, Germany

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Chang Gung Memorial Hospital - LinKou Branch

Taoyuan District, 333, Taiwan

Location

St. Bartholomew's Hospital

West Smithfield, London, EC1A 7BE, United Kingdom

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

ADI PEG20

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

The study was terminated early due to lack of efficacy and slow enrollment; therefore, only 22 of the planned 45 subjects were enrolled, treated, and evaluated for study endpoints.

Results Point of Contact

• Title: Jonathan Skipper PhD
• Organization: Ludwig Institute for Cancer Research

jskipper@lcr.org

12124501539

Study Officials

• Lee M Krug, MD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2010
• First Posted: December 24, 2010
• Study Start: January 1, 2011
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: October 25, 2022
• Results First Posted: June 6, 2017

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share

Locations

US (2); DE (1); GB (1); TW (3); BE (1)