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

NCT02102022 | Terminated Phase 1

• 1 other identifier: POLARIS2013-001
• Study Type: interventional
• Target: 140
• Locations: 6 countries
• Sites: 35

Brief 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 (BICR).

Conditions

Advanced Gastrointestinal (GI) Malignancies; Hepatocellular Carcinoma; Gastric Cancer; Colorectal Cancer

Keywords

argininosuccinate synthetase; arginine; arginine deiminase

Outcome Measures

Primary Outcomes (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.

  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)

• Progression free survival (PFS)

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

• Overall survival (OS)

  Date of first study drug administration through study completion

• Duration of response (DoR)

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

• Disease control rate (DCR)

  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.

• Pharmacodynamics

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

Study Arms (1)

ADI-PEG 20 plus modified FOLFOX6

EXPERIMENTAL

Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) In combination with modified FOLFOX6, every 2 weeks, intravenous (IV) / IV bolus

Drug: ADI-PEG 20 plus modified FOLFOX6

Interventions

ADI-PEG 20 plus modified FOLFOX6 DRUG

Also known as: pegargiminase

ADI-PEG 20 plus modified FOLFOX6

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Polaris Group: lead

Study Sites (35)

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

The University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

The Chinese People's Liberation Army 81 Hospital

Nanjing, Jiangsu, 210000, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610000, China

Location

IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, Lombardy, 20122, Italy

Location

National Cancer Institute of Napoli IRCCS G. Pascale

Napoli, 80131, Italy

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

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

Seoul, 06591, South Korea

Location

Changhua Christian Hospital

Changhua, 500, Taiwan

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

Chang Gung Medical Foundation - Kaohsiung

Kaohsiung City, 833, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

Chi Mei Medical Center

Tainan, 71004, Taiwan

Location

Chi Mei Hospital, Liouying

Tainan, 73657, Taiwan

Location

Mackay Memorial Hospital

Taipei, 10491, Taiwan

Location

Taipei Medical University Hospital

Taipei, 11031, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

Tri-Service General Hospital

Taipei, Taiwan

Location

Chang Gung Medical Foundation - Linkou

Taoyuan District, Taiwan

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Wirral, CH63 4JY, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Guy's & St Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms; Carcinoma, Hepatocellular; Stomach Neoplasms; Colorectal Neoplasms

Interventions

ADI PEG20

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• James Harding, MD

  Memorial Sloan-Kettering Cancer Center (MSKCC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2014
• First Posted: April 2, 2014
• Study Start: November 1, 2014
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2020
• Last Updated: April 25, 2022

Record last verified: 2019-05

Locations

IT (2); KR (6); TW (11); GB (4); US (10); CN (2)