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Advanced Gastrointestinal (GI) MalignanciesPhase 1/2NCT02102022

Ph 1-2 Study ADI-PEG 20 Plus FOLFOX in Subjects With Advanced GI Malignancies Focusing on Hepatocellular Carcinoma

A Phase 1/2 study testing ADI-PEG 20 plus modified FOLFOX6 in people with Advanced Gastrointestinal (GI) Malignancies and Hepatocellular Carcinoma, run by Polaris Group at 35 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Phase 1: Assessment of safety and tolerability of ADI-PEG 20 in combination with folinic acid (leucovorin), fluorouracil and oxaliplatin (FOLFOX) in advanced GI malignancies. Phase 2: Assessment of the objective response rate (ORR), measured by RECIST 1.1 criteria as assessed by blinded independent central review… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ADI-PEG 20 plus modified FOLFOX6
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
140 participants
Where
35 sitesin 6 countries
Study dates
Nov 2014to Feb 2020
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • Advanced histologically or cytologically proven HCC (except with prior liver transplantation).
  • Treatment with at least 2 prior systemic therapy regimens.
  • Child-Pugh grade A. Child-Pugh status should be determined based on clinical findings and laboratory data during the screening period (Appendix C).
  • Measurable disease using RECIST 1.1 criteria (Appendix A). At least 1 measurable lesion must be present. Subjects who have received local-regional therapies are eligible, provided that they have either a target lesion which has not been treated with local therapy and/or the target lesion(s) within the field of the local regional therapy has shown an increase of ≥ 20% in size. Local-regional therapy must be completed at least 4 weeks prior to the baseline CT scan.
  • ECOG performance status of 0 - 1.
  • Expected survival of at least 3 months.
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  • Age ≥ 18 years.
  • Fully recovered from any prior surgery and no major surgery within 4 weeks of initiating treatment. Surgery or procedure for placement of vascular access devices is exempt from this period.
  • Subjects must agree to use at least one form of highly effective contraception or agree to refrain from intercourse for the duration of the study. Contraceptive use must be continued until at least 30 days after the last administration of ADI-PEG 20 and at least 90 days after the last administration of FOLFOX. For female subjects, a serum human chorionic gonadotropin (HCG) pregnancy test must be negative before entry into the study. If HCG pregnancy test is positive, further evaluation to rule out pregnancy must be performed according to GCP before this patient is claimed eligible.
  • Informed consent must be obtained prior to study initiation.
  • No concurrent investigational studies are allowed.
  • Total bilirubin < 1.5 x upper limit of normal range.
  • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x upper limit of normal range.
  • Absolute neutrophil count (ANC) > 1500/μL.
  • Platelets > 75,000/μL.
  • Serum uric acid ≤ 8 mg/dL (with or without medication control).
  • Serum creatinine ≤ 1.5 x the upper limit of normal range, or, if serum creatinine >1.5 x the upper limit of normal range, then the creatinine clearance must be ≥ 60 mL/min/1.73 m2 (calculated using the Jelliffe equation: calculated creatinine clearance = 98 - 0.8 [age (yrs.) - 20] /serum creatinine (x 0.9 if female).
  • Brain metastases are allowed if well controlled and without seizures.
  • Serum albumin level ≥ 2.8 g/dL.
  • Prothrombin time (PT)-international normalized ratio (INR): PT <6 seconds above control or INR <1.7. Subjects on Coumadin anti-coagulants are to receive only 1 point for their INR status.
  • Subjects with active hepatitis B or C on anti-viremic compounds may remain on such treatment, except for interferon.

Who cannot join

  • A subject will not be eligible for study participation if he/she meets any of the exclusion criteria:
  • Serious infection requiring treatment with systemically administered antibiotics at the time of study entrance, or an infection requiring systemic antibiotic therapy within 7 days prior to the first dose of study treatment.
  • Pregnancy or lactation.
  • Expected non-compliance.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), cardiac arrhythmia, or psychiatric illness.
  • Subjects who have had any anticancer treatment prior to entering the study and have not recovered to baseline (except alopecia) or ≤ Grade 1 AEs, or deemed irreversible from the effects of prior cancer therapy. AEs > Grade 1 that are not considered a safety risk by the Sponsor and investigator may be allowed upon agreement with both.
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  • Subjects with history of another primary cancer, including co-existent second malignancy, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present or in the opinion of the investigator will not affect patient outcome.
  • Subjects who had been treated with ADI-PEG 20 previously.
  • History of seizure disorder not related to underlying cancer.
  • Known HIV positivity (testing not required).
  • Known allergy to pegylated compounds.
  • Known allergy to E. coli drug products (such as GMCSF).
  • Known allergy to oxaliplatin or other platinum compounds.
  • Prior grade 2 or higher neuropathy from prior platinum unless neuropathy is currently ≤ grade 1.
  • Contraindications to fluorouracil
  • Subjects with poor nutritional state.
  • Known depressed bone marrow function.
  • Subjects with potentially serious infections.
  • Known allergy to fluorouracil.

Trial locations and contacts

35 sites in 6 countries.

35 sites in 6 countries

Taiwan11 sites

  • Changhua Christian Hospital

    Changhua, 500

  • Kaohsiung Medical University Chung-Ho Memorial Hospital

    Kaohsiung City, 807

  • Chang Gung Medical Foundation - Kaohsiung

    Kaohsiung City, 833

  • National Cheng Kung University Hospital

    Tainan, 704

  • Chi Mei Medical Center

    Tainan, 71004

  • Chi Mei Hospital, Liouying

    Tainan, 73657

  • Mackay Memorial Hospital

    Taipei, 10491

  • Taipei Medical University Hospital

    Taipei, 11031

  • Taipei Veterans General Hospital

    Taipei

  • Tri-Service General Hospital

    Taipei

  • Chang Gung Medical Foundation - Linkou

    Taoyuan

Other trials in Taiwan

United States10 sites

  • Emory University

    Atlanta, Georgia, 30322

  • The University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • California Pacific Medical Center

    San Francisco, California, 94115

  • University of Washington

    Seattle, Washington, 98109

  • Washington University

    St Louis, Missouri, 63110

  • The University of Kansas Cancer Center

    Westwood, Kansas, 66205

Other trials in United States

South Korea6 sites

  • Pusan National University Hospital

    Busan, 49241

  • Seoul National University Bundang Hospital

    Seongnam-si, Gyeonggi-do, 13620

  • Seoul National University Hospital

    Seoul, 03080

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

  • The Catholic University of Korea, Seoul ST. Mary's Hospital

    Seoul, 06591

Other trials in South Korea

United Kingdom4 sites

  • The Clatterbridge Cancer Centre NHS Foundation Trust

    Bebington, Wirral, CH63 4JY

  • Royal Free Hospital

    London, NW3 2QG

  • Guy's & St Thomas' NHS Foundation Trust

    London, SE1 9RT

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

Other trials in United Kingdom

China2 sites

  • West China Hospital, Sichuan University

    Chengdu, Sichuan, 610000

  • The Chinese People's Liberation Army 81 Hospital

    Nanjing, Jiangsu, 210000

Other trials in China

Italy2 sites

  • IRCCS Ca Granda Ospedale Maggiore Policlinico

    Milan, Lombardy, 20122

  • National Cancer Institute of Napoli IRCCS G. Pascale

    Naples, 80131

Other trials in Italy

About this study

Official title: Phase 1/2 Study of ADI-PEG 20 Plus FOLFOX in Subjects With Advanced Gastrointestinal Malignancies Focusing on Hepatocellular Carcinoma

Phase 1: Assessment of safety and tolerability of ADI-PEG 20 in combination with folinic acid (leucovorin), fluorouracil and oxaliplatin (FOLFOX) in advanced GI malignancies.

Phase 2: Assessment of the objective response rate (ORR), measured by RECIST 1.1 criteria as assessed by blinded independent central review (BICR).

Read the detailed description

Phase 1:The primary objective of the dose escalation portion of this study was to assess the safety and tolerability of ADI-PEG 20 in combination with folinic acid (leucovorin), fluorouracil (5-FU), and oxaliplatin (mFOLFOX6) in advanced GI malignancies. The primary objective of the maximum tolerated dose (MTD) expansion phase (recommended phase 2 dose [RP2D]) of this study was to determine preliminary estimates of efficacy, measured by RECIST 1.1 criteria, for ADI-PEG 20 in combination with FOLFOX in hepatocellular carcinoma (HCC), gastro-esophageal cancer (GEC), and colorectal cancer (CRC).

Phase 2: The primary objective of this single arm trial is ORR. Based on a two-sided exact test of a one-sample proportion with an alpha of 0.05, under a presumed ORR of 22%, there is 80% power to yield 95% confidence interval of 15-26%, which will require 46 objective responses in 225 subjects. A futility analysis will be described in the Statistical Analysis Plan.

Being tested
ADI-PEG 20 plus modified FOLFOX6
Keywords
argininosuccinate synthetase, arginine, arginine deiminase
Medical subject headings
Neoplasms, Carcinoma, Hepatocellular, Stomach Neoplasms, Colorectal Neoplasms

What participants receive

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

  • ADI-PEG 20 plus modified FOLFOX6Drug

    Also called pegargiminase

Study groups in NCT02102022
Study groupRoleWhat they receive
ADI-PEG 20 plus modified FOLFOX6ExperimentalDose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) In combination with modified FOLFOX6, every 2 weeks, intravenous (IV) / IV bolus
Receives: Drug: ADI-PEG 20 plus modified FOLFOX6

What is being measured

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

  1. Objective response rate (ORR)

    The percent of subjects who exhibit each level of tumor response, measured by RECIST 1.1 criteria as assessed by blinded independent central review.

    Measured: Date of first study drug administration to the date of disease progression (measured every 8 weeks) or death (whichever occurs first), up to 24 months

Secondary outcomes (8)

  1. Progression free survival (PFS)

    Time from the first dose until objective tumor progression or death from any cause

    Measured: Date of first study drug administration to the date of disease progression (measured every 8 weeks) or death (whichever occurs first), 12 months anticipated

  2. Overall survival (OS)

    The time from first treatment with ADI-PEG 20 until death or censoring

    Measured: Date of first study drug administration through study completion

  3. Duration of response (DoR)

    the time in weeks between the first occurrence of objective response and the development of progressive disease or death

    Measured: From date of first response until the date of documented progression or date of death, 12 month in average

  4. Disease control rate (DCR)

    the proportion of subjects at each post-baseline assessment who exhibit tumor response of complete response, partial response or stable disease

    Measured: Date of first study drug administration to the date of disease progression (measured every 8 weeks) or death (whichever occurs first), up to 24 months.

  5. Pharmacodynamics

    Blood levels of arginine and citrulline

    Measured: At week 1, 5, 9, 13, 17, 21 prior to ADI-PEG 20 administration

  6. Pharmacokinetics Variable

    Peripheral blood levels of ADI-PEG 20

    Measured: At week 1, 5, 9, 13, 17, 21 prior to ADI-PEG 20 administration

  7. Immunogenicity

    antibodies to ADI-PEG 20

    Measured: At week 1, 5, 9, 13, 17, 21 prior to ADI-PEG 20 administration

  8. AFP (alpha feto-protein) changes

    Maximal percent changes of AFP during the course of study compared to AFP at baseline

    Measured: At baseline, week3, 7, 11, 15, 19, 23 and end of treatment

Timeline

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

  1. First posted2 Apr 2014 (estimated)
  2. Study startNov 2014
  3. Primary completionFeb 2020
  4. Study completionFeb 2020

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
140 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02102022
Sponsor's protocol ID
POLARIS2013-001
Status last verified
May 2019
First submitted
28 Mar 2014
Last updated
25 Apr 2022
Results posted
No
Data monitoring committee
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ADI-PEG 20 plus modified FOLFOX6 in people with Advanced Gastrointestinal (GI) Malignancies and Hepatocellular Carcinoma, run by Polaris Group at 35 sites in 6 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 21 inclusion and 19 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 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in Taiwan, United States, South Korea, United Kingdom, China and 1 more country. 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?

The study was stopped early. Results are not available in the source record.

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?

Objective response rate (ORR) (time frame: Date of first study drug administration to the date of disease progression (measured every 8 weeks) or death (whichever occurs first), up to 24 months). 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 NCT02102022.

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 Apr 2022.

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