Metastatic MelanomaPhase 1/2NCT00520299

Study of ADI-PEG 20 in Patients With Advanced Melanoma

A Phase 1/2 study testing ADI PEG 20 in people with Metastatic Melanoma and Skin Cancer, run by Ludwig Institute for Cancer Research at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Metastatic Melanoma, Skin Cancer, Neoplasm
What is being tested?: ADI PEG 20
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 31 participants
Where: 2 sitesUnited States
Study dates: Jul 2007to Mar 2010
Phase: Phase 1/2
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

Histologically confirmed malignant melanoma, American Joint Committee on Cancer (AJCC) stage III (unresectable) or IV. Subjects with uveal and mucosal melanomas were eligible.
Measurable disease using the Response Evaluation Criteria in Solid Tumors (RECIST).
Pathology slides reviewed by the Memorial Hospital Department of Pathology or New York University (NYU) Department of Pathology for confirmation of melanoma diagnosis.
Karnofsky performance status of 80% or more.
Adequate organ and marrow function, as defined below:
white blood cell count ≥ 3000/µL

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absolute neutrophil count ≥ 1500/µL
platelet count ≥ 100,000/µL
total bilirubin ≤ 2.5 x institutional upper limit of normal (ULN)
lactate dehydrogenase ≤ 1.5 x institutional ULN
albumin ≥ 3.0 mg/dL
creatinine ≤ 2.0 mg/dL
Expected survival of at least 3 months.
Age ≥ 18 years.
Able and willing to give valid written informed consent.

Who cannot join

Receipt of chemotherapy, immunotherapy, or radiotherapy within 3 weeks prior to first dosing of study agent or lack of recovery from adverse events (AEs) due to agents administered more than 3 weeks earlier. For nitrosoureas, at least 6 weeks must have elapsed.
Any other malignancy that required concomitant therapy.
Any medical condition that could have made it difficult for the subject to complete the full course of treatments, at the discretion of the Principal Investigator or co-Principal Investigators.
Metastatic disease to the central nervous system, unless treated and stable.
Known human immunodeficiency virus (HIV) positivity.
Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.

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Lack of availability for clinical follow-up assessments.
Participation in any other clinical trial involving another investigational agent within 3 weeks prior to enrollment.
Pregnant women or women who were nursing. Women of child-bearing potential and sexually active men must have used appropriate contraception during the course of this study. Women of child-bearing potential must not have been pregnant (negative β human chorionic gonadotropin within 2 weeks of treatment) or nursing during treatment.
History of seizure disorder.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

NYU Cancer Institute
New York, New York, 10016
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021

Other trials in United States

About this study

Official title: Phase 1/2 Study of ADI-SS PEG 20,000mw in Patients With Advanced Melanoma

This was a phase 1/2, open-label, dose-escalation study of arginine deiminase linked via succinimidyl succinate to polyethylene glycol of 20,000 molecular weight (ADI-PEG 20) in subjects with advanced melanoma. ADI-PEG 20 was administered intramuscularly (IM) at escalating doses weekly for 9 weeks (cycle 1) or 8 weeks (subsequent cycles). The primary objectives were to the establish the safety, tolerability, and clinical efficacy of ADI-PEG 20. Secondary objectives included evaluation of the metabolic activity by [18F]-fluorodeoxyglucose positron emission tomography (FDG PET), pharmacodynamics, correlation of immunogenicity with clinical response, and correlation of argininosuccinate synthetase (ASS) tumor expression with clinical response.

Read the detailed description

A 3+3 design was implemented during phase 1, in which 3 to 6 subjects were enrolled sequentially into the following escalating dose cohorts:

Cohort 1 (40 IU/m^2)
Cohort 2 (80 IU/m^2)
Cohort 3 (160 IU/m^2)

Subjects were monitored for dose-limiting toxicity (DLT) during the first 2 weeks of cycle 1, with DLT defined as any grade 3 or higher toxicity. The maximum tolerated dose (MTD) was defined as the cohort in which < 33% of subjects (ie, 0/3 or 1/6 subjects in a cohort) experienced DLT. In phase 2, the MTD cohort was expanded in up to 25 patients.

Subjects who completed treatment in cycle 1 without DLT were eligible to initiate cycle 2 at week 10 provided that a computed tomography (CT) scan showed either enlargement of existing disease without accompanying symptoms OR stable disease or improvement with no unacceptable toxicity. The same radiologic criteria applied for initiation of subsequent cycles. Subjects could continue to receive study treatment until disease progression.

Conditions: Metastatic Melanoma, Skin Cancer, Neoplasm
Being tested: ADI PEG 20
Keywords: metastatic melanoma, ADI, ADI-PEG 20, ADI SS PEG 20,000mw, arginine, enzyme therapy
Medical subject headings: Melanoma, Skin Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ADI PEG 20Drug
Also called ADI-SS PEG 20,000 mw, ADI
Intramuscular injections were administered into the deltoid, gluteal, or quadricep muscles once weekly (± 2 days) for 9 weeks during cycle 1 and 8 weeks during subsequent cycles

Study groups in NCT00520299
Study group	Role	What they receive
Cohort 1	Experimental	Subjects received ADI-PEG 20 at a dose of 40 IU/m^2 Receives: Drug: ADI PEG 20
Cohort 2	Experimental	Subjects received ADI-PEG 20 at a dose of 80 IU/m^2 Receives: Drug: ADI PEG 20
Cohort 3	Experimental	Subjects received ADI-PEG 20 at a dose of 160 IU/m^2 Receives: Drug: ADI PEG 20

What is being measured

The primary outcome is the main question the study is designed to answer.

Assessment of Safety and Tolerability of ADI-PEG 20
Analysis of treatment-emergent adverse events (TEAEs) reported from clinical laboratory tests, physical examinations, and vital signs.
Measured: Every 1 to 2 weeks for up to 12 months
Best Overall Clinical Tumor Response
Clinical tumor responses were evaluated using disease imaging (CT preferred) performed at baseline and at the end of every cycle. Responses were categorized according to RECIST. 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 8 to 9 weeks for up to 12 months

Secondary outcomes (6)

Metabolic Tumor Response
Metabolic tumor responses were evaluated using fluorodeoxyglucose (FDG) positron emission tomography (PET) at baseline, on day 4, and at the end of every cycle.
Measured: Every 8 to 9 weeks for up to 12 months
Summary of ADI-PEG 20 Plasma Concentrations Over Time
Blood samples were collected on day 1 (pre-injection), day 4, day 8, and every 7 days thereafter for ADI-PEG 20 plasma concentrations.
Measured: Up to 12 months
Summary of Plasma Arginine Levels Over Time
Blood samples were collected at baseline, day 1 (pre-injection), day 4, day 8, and every 7 days thereafter for plasma arginine levels.
Measured: Up to 9 months
Summary of Plasma Citrulline Levels Over Time
Blood samples were collected at baseline, day 1 (pre-injection), day 4, day 8, and every 7 days thereafter for plasma citrulline levels.
Measured: Up to 9 months
Summary of ADI-PEG 20 Immunogenicity Over Time
Blood samples were collected at baseline, day 1 (pre-injection), day 4, day 8, and every 7 days thereafter for detection of anti-ADI antibodies.
Measured: Up to 12 months
Correlation Between ASS Tumor Expression and Clinical Response
Expression of ASS was analyzed by immunohistochemistry in tumor samples (archived or biopsy) at baseline and compared with overall best clinical response per RECIST. ASS tumor expression is categorized as either negative or ≤ 5% positive tumor cells.
Measured: Up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2007Mar 2010

First posted24 Aug 2007 (estimated)
Study startJul 2007
Primary completionMar 2010
Study completionMar 2010

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Metastatic MelanomaStudies 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 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00520299
Sponsor's protocol ID: LUD2005-007
Other IDs: MSKCC IRB #06-165, NYU IRB #07-053
Status last verified: Oct 2022
First submitted: 22 Aug 2007
Last updated: 25 Oct 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes

Publications

Ott PA, Carvajal RD, Pandit-Taskar N, Jungbluth AA, Hoffman EW, Wu BW, Bomalaski JS, Venhaus R, Pan L, Old LJ, Pavlick AC, Wolchok JD. Phase I/II study of pegylated arginine deiminase (ADI-PEG 20) in patients with advanced melanoma. Invest New Drugs. 2013 Apr;31(2):425-34. doi: 10.1007/s10637-012-9862-2. Epub 2012 Aug 5.
PubMed 22864522

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
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Active, not recruitingPhase 1/2
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All Metastatic Melanoma trials

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 1/2 Study of ADI-SS PEG 20,000mw in Patients With Advanced Melanoma
ClinicalTrials.gov ID: NCT00520299
Acronym / sponsor ID: LUD2005-007
Conditions: Metastatic Melanoma, Skin Cancer, Neoplasm
Keywords: metastatic melanoma, ADI, ADI-PEG 20, ADI SS PEG 20,000mw, arginine, enzyme therapy
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 31 participants (actual)
Lead sponsor: Ludwig Institute for Cancer ResearchUniversity, hospital or other
Collaborators: Memorial Sloan Kettering Cancer Center, NYU Langone Health
Study start: Jul 2007
Primary completion: Mar 2010 (actual)
Study completion: Mar 2010 (actual)
First posted: 24 Aug 2007 (estimated)
Results: Posted 26 Apr 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

A 3+3 design was implemented during phase 1, in which 3 to 6 subjects were enrolled sequentially into the following escalating dose cohorts:

Cohort 1 (40 IU/m^2)
Cohort 2 (80 IU/m^2)
Cohort 3 (160 IU/m^2)

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Cohort 1	Experimental	Drug: ADI PEG 20Subjects received ADI-PEG 20 at a dose of 40 IU/m^2
Cohort 2	Experimental	Drug: ADI PEG 20Subjects received ADI-PEG 20 at a dose of 80 IU/m^2
Cohort 3	Experimental	Drug: ADI PEG 20Subjects received ADI-PEG 20 at a dose of 160 IU/m^2

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (15 listed)

Histologically confirmed malignant melanoma, American Joint Committee on Cancer (AJCC) stage III (unresectable) or IV. Subjects with uveal and mucosal melanomas were eligible.
Measurable disease using the Response Evaluation Criteria in Solid Tumors (RECIST).
Pathology slides reviewed by the Memorial Hospital Department of Pathology or New York University (NYU) Department of Pathology for confirmation of melanoma diagnosis.
Karnofsky performance status of 80% or more.
Adequate organ and marrow function, as defined below:

Key exclusion criteria (10 listed)

Receipt of chemotherapy, immunotherapy, or radiotherapy within 3 weeks prior to first dosing of study agent or lack of recovery from adverse events (AEs) due to agents administered more than 3 weeks earlier. For nitrosoureas, at least 6 weeks must have elapsed.
Any other malignancy that required concomitant therapy.
Any medical condition that could have made it difficult for the subject to complete the full course of treatments, at the discretion of the Principal Investigator or co-Principal Investigators.
Metastatic disease to the central nervous system, unless treated and stable.
Known human immunodeficiency virus (HIV) positivity.

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 20Also: ADI-SS PEG 20,000 mw, ADIIntramuscular injections were administered into the deltoid, gluteal, or quadricep muscles once weekly (± 2 days) for 9 weeks during cycle 1 and 8 weeks during subsequent cycles	Drug	Cohort 1, Cohort 2, Cohort 3

Primary outcome

Assessment of Safety and Tolerability of ADI-PEG 20
Time frame: Every 1 to 2 weeks for up to 12 months
Analysis of treatment-emergent adverse events (TEAEs) reported from clinical laboratory tests, physical examinations, and vital signs.
Best Overall Clinical Tumor Response
Time frame: Every 8 to 9 weeks for up to 12 months
Clinical tumor responses were evaluated using disease imaging (CT preferred) performed at baseline and at the end of every cycle. Responses were categorized according to RECIST. 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.

6 secondary outcomes

Metabolic Tumor Response
Time frame: Every 8 to 9 weeks for up to 12 months
Summary of ADI-PEG 20 Plasma Concentrations Over Time
Time frame: Up to 12 months
Summary of Plasma Arginine Levels Over Time
Time frame: Up to 9 months
Summary of Plasma Citrulline Levels Over Time
Time frame: Up to 9 months
Summary of ADI-PEG 20 Immunogenicity Over Time
Time frame: Up to 12 months
Correlation Between ASS Tumor Expression and Clinical Response
Time frame: Up to 12 months

Results and safety

Results posted to the registry on 26 Apr 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1: ADI-PEG 20 40 IU/m^2/Week	6	6
Cohort 2: ADI-PEG 20 80 IU/m^2/Week	6	3
Cohort 3: ADI-PEG 20 160 IU/m^2/Week	19	13

Primary outcome: Assessment of Safety and Tolerability of ADI-PEG 20

Time frame: Every 1 to 2 weeks for up to 12 months. Number. Unit: participants

Measure	Cohort 1: ADI-PEG 20 40 IU/m^2/Week n = 6	Cohort 2: ADI-PEG 20 80 IU/m^2/Week n = 6	Cohort 3: ADI-PEG 20 160 IU/m^2/Week n = 19
Any TEAE	6	6	19
Grade 3 TEAE	1	2	4
Grade 4 TEAE	0	1	1
Grade 5 TEAE (Death)	0	0	1
Treatment-related TEAE	5	5	17
SAE	4	1	6
TEAE leading to withdrawal	0	1	3

Population analysed: Safety Analysis Set (all subjects who received at least 1 dose of ADI-PEG 20)

Primary outcome: Best Overall Clinical Tumor Response

Time frame: Every 8 to 9 weeks for up to 12 months. Number. Unit: participants

Measure	Cohort 1: ADI-PEG 20 40 IU/m^2/Week n = 6	Cohort 2: ADI-PEG 20 80 IU/m^2/Week n = 6	Cohort 3: ADI-PEG 20 160 IU/m^2/Week n = 17
Complete/partial response	0	0	0
Stable disease	3	2	4
Progressive disease	3	4	13

Population analysed: Includes all subjects who completed the study as planned or had tumor progression during the study

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: All adverse events (AEs) occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs occurring after the first dose of study drug were considered treatment emergent (i.e., TEAEs).. Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1: ADI-PEG 20 40 IU/m^2/Week	4 of 6 (66.7%)	6 of 6 (100%)	0 of 6
Cohort 2: ADI-PEG 20 80 IU/m^2/Week	1 of 6 (16.7%)	6 of 6 (100%)	0 of 6
Cohort 3: ADI-PEG 20 160 IU/m^2/Week	6 of 19 (31.6%)	19 of 19 (100%)	1 of 19

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.
Results publication: PubMed 22864522Ott PA, Carvajal RD, Pandit-Taskar N, Jungbluth AA, Hoffman EW, Wu BW, Bomalaski JS, Venhaus R, Pan L, Old LJ, Pavlick AC, Wolchok JD. Phase I/II study of pegylated arginine deiminase (ADI-PEG 20) in patients with advanced melanoma. Invest New Drugs. 2013 Apr;31(2):425-34. doi: 10.1007/s10637-012-9862-2. Epub 2012 Aug 5.
Individual participant dataSharing planned: Yes

Related trials for Metastatic Melanoma

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
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Active, not recruitingPhase 1/2
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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.

Jedd Wolchok, MD, PhD principal investigator

Memorial Sloan Kettering Cancer Center

Anna Pavlick, DO principal investigator

New York University Cancer Institute

Gary Schwartz, MD principal investigator

Memorial Sloan Kettering Cancer Center

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ADI PEG 20 in people with Metastatic Melanoma and Skin Cancer, run by Ludwig Institute for Cancer Research at 2 sites in United States.

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 15 inclusion and 10 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: finished, 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 2 sites in United States. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 26 Apr 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?

Assessment of Safety and Tolerability of ADI-PEG 20 (time frame: Every 1 to 2 weeks for up to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00520299, which also lists 1 linked publication.

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.