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

NCT ID: NCT02102022

Last Updated: 2022-04-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

140 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-11-30

Study Completion Date

2020-02-29

Brief Summary

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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).

Detailed Description

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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.

Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ADI-PEG 20 plus modified FOLFOX6

Dose: 36 mg/m2 given weekly

Route of Administration: Intramuscular (IM)

In combination with modified FOLFOX6, every 2 weeks, intravenous (IV) / IV bolus

Group Type EXPERIMENTAL

ADI-PEG 20 plus modified FOLFOX6

Intervention Type DRUG

Interventions

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ADI-PEG 20 plus modified FOLFOX6

Intervention Type DRUG

Other Intervention Names

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pegargiminase

Eligibility Criteria

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Inclusion Criteria

1. Advanced histologically or cytologically proven HCC (except with prior liver transplantation).
2. Treatment with at least 2 prior systemic therapy regimens.
3. Child-Pugh grade A. Child-Pugh status should be determined based on clinical findings and laboratory data during the screening period (Appendix C).
4. 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.
5. ECOG performance status of 0 - 1.
6. Expected survival of at least 3 months.
7. Age ≥ 18 years.
8. 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.
9. 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.
10. Informed consent must be obtained prior to study initiation.
11. No concurrent investigational studies are allowed.
12. Total bilirubin \< 1.5 x upper limit of normal range.
13. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x upper limit of normal range.
14. Absolute neutrophil count (ANC) \> 1500/μL.
15. Platelets \> 75,000/μL.
16. Serum uric acid ≤ 8 mg/dL (with or without medication control).
17. 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).
18. Brain metastases are allowed if well controlled and without seizures.
19. Serum albumin level ≥ 2.8 g/dL.
20. 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.
21. Subjects with active hepatitis B or C on anti-viremic compounds may remain on such treatment, except for interferon.

Exclusion Criteria

1. 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.
2. Pregnancy or lactation.
3. Expected non-compliance.
4. 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.
5. 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.
6. 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.
7. Subjects who had been treated with ADI-PEG 20 previously.
8. History of seizure disorder not related to underlying cancer.
9. Known HIV positivity (testing not required).
10. Known allergy to pegylated compounds.
11. Known allergy to E. coli drug products (such as GMCSF).
12. Known allergy to oxaliplatin or other platinum compounds.
13. Prior grade 2 or higher neuropathy from prior platinum unless neuropathy is currently ≤ grade 1.
14. Contraindications to fluorouracil

1. Subjects with poor nutritional state.
2. Known depressed bone marrow function.
3. Subjects with potentially serious infections.
4. Known allergy to fluorouracil.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Polaris Group

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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James Harding, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan-Kettering Cancer Center (MSKCC)

Locations

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California Pacific Medical Center

San Francisco, California, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

The University of Chicago Medical Center

Chicago, Illinois, United States

Site Status

The University of Kansas Cancer Center

Westwood, Kansas, United States

Site Status

Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

The Chinese People's Liberation Army 81 Hospital

Nanjing, Jiangsu, China

Site Status

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Site Status

IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, Lombardy, Italy

Site Status

National Cancer Institute of Napoli IRCCS G. Pascale

Napoli, , Italy

Site Status

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Site Status

Pusan National University Hospital

Busan, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

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

Seoul, , South Korea

Site Status

Changhua Christian Hospital

Changhua, , Taiwan

Site Status

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

Chang Gung Medical Foundation - Kaohsiung

Kaohsiung City, , Taiwan

Site Status

National Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status

Chi Mei Medical Center

Tainan City, , Taiwan

Site Status

Chi Mei Hospital, Liouying

Tainan City, , Taiwan

Site Status

Mackay Memorial Hospital

Taipei, , Taiwan

Site Status

Taipei Medical University Hospital

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Tri-Service General Hospital

Taipei, , Taiwan

Site Status

Chang Gung Medical Foundation - Linkou

Taoyuan District, , Taiwan

Site Status

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Wirral, United Kingdom

Site Status

Royal Free Hospital

London, , United Kingdom

Site Status

Guy's & St Thomas' NHS Foundation Trust

London, , United Kingdom

Site Status

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

Countries

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United States China Italy South Korea Taiwan United Kingdom

Other Identifiers

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POLARIS2013-001

Identifier Type: -

Identifier Source: org_study_id

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