Small Cell Lung CancerPhase 2NCT01266018
Study of ADI-PEG 20 in Patients With Relapsed Sensitive or Refractory Small Cell Lung Cancer
A Phase 2 study testing ADI-PEG 20 (Arginine deiminase pegylated) in people with Small Cell Lung Cancer, run by Ludwig Institute for Cancer Research at 8 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Cancer
- What is being tested?
- ADI-PEG 20 (Arginine deiminase pegylated)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 8 sitesin 5 countries
- Study dates
- Jan 2011to Jan 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
- Able and willing to give valid written informed consent
Who cannot join
- 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
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- 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
Trial locations and contacts
8 sites in 5 countries.
8 sites in 5 countries
Taiwan3 sites
National Cheng Kung University Hospital
Tainan, 704
National Taiwan University Hospital
Taipei, 10002
Chang Gung Memorial Hospital - LinKou Branch
Taoyuan, 333
United States2 sites
Duke University Medical Center
Durham, North Carolina, 27710
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
United Kingdom1 site
St. Bartholomew's Hospital
West Smithfield, London, EC1A 7BE
About this study
Official title: 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.
Read the 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.
- Conditions
- Small Cell Lung Cancer
- Being tested
- ADI-PEG 20 (Arginine deiminase pegylated)
- Keywords
- small cell lung cancer, SCLC, ADI-PEG 20, arginine deiminase pegylated
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADI-PEG 20 (Arginine deiminase pegylated)Drug
Also called ADI, 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)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: ADI-PEG 20 (Arginine deiminase pegylated) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Every 4 to 8 weeks for up to 16 weeks
Secondary outcomes (4)
Assessment of Safety of Arginine Deiminase Pegylated (ADI-PEG) 20
Analysis of treatment-emergent adverse events (TEAEs) reported from clinical laboratory tests, physical examinations, and vital signs.
Measured: Every 1 to 4 weeks for up to 16 weeks
Assessment of Pharmacodynamics of ADI-PEG 20
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.
Measured: Every 1 to 4 weeks for up to 16 weeks
Assessment of Immunogenicity of ADI-PEG 20
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.
Measured: Every 1 to 4 weeks for up to 16 weeks
Assessment of Overall Survival
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.
Measured: Every 4 weeks for up to 16 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2010 (estimated)
- Study startJan 2011
- Primary completionJan 2014
- Study completionJan 2014
Why it stopped: Lack of efficacy in Cohort 2; slow enrollment in Cohort 1
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig Institute for Cancer Research
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Sponsor
- Investigators
- Lee M Krug, MD, Study chair, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01266018
- Sponsor's protocol ID
- LUD2009-007
- Other IDs
- Pro00022622
- Status last verified
- Oct 2022
- First submitted
- 22 Dec 2010
- Last updated
- 25 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of ADI-PEG 20 in Patients With Relapsed Sensitive or Refractory Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT01266018
- Acronym / sponsor ID
- LUD2009-007
- Conditions
- Small Cell Lung Cancer
- Keywords
- small cell lung cancer, SCLC, ADI-PEG 20, arginine deiminase pegylated
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of efficacy in Cohort 2; slow enrollment in Cohort 1
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Ludwig Institute for Cancer ResearchUniversity, hospital or other
- 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
- Study start
- Jan 2011
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 24 Dec 2010 (estimated)
- Results
- Posted 6 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Sensitive Disease | Experimental | Drug: ADI-PEG 20 (Arginine deiminase pegylated)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. |
| Cohort 2: Refractory Disease | Experimental | Drug: ADI-PEG 20 (Arginine deiminase pegylated)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ADI-PEG 20 (Arginine deiminase pegylated)Also: ADI, Arginine deiminase pegylatedADI-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) | Drug | Cohort 1: Sensitive Disease, Cohort 2: Refractory Disease |
Primary outcome
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.
4 secondary outcomes
Assessment of Safety of Arginine Deiminase Pegylated (ADI-PEG) 20
Time frame: Every 1 to 4 weeks for up to 16 weeks
Assessment of Pharmacodynamics of ADI-PEG 20
Time frame: Every 1 to 4 weeks for up to 16 weeks
Assessment of Immunogenicity of ADI-PEG 20
Time frame: Every 1 to 4 weeks for up to 16 weeks
Assessment of Overall Survival
Time frame: Every 4 weeks for up to 16 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lee M Krug, MD study chair
Memorial Sloan Kettering Cancer Center
8 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ADI-PEG 20 (Arginine deiminase pegylated) in people with Small Cell Lung Cancer, run by Ludwig Institute for Cancer Research at 8 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Taiwan, United States, Belgium, Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best Overall Response (time frame: Every 4 to 8 weeks for up to 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2022.