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Recombinant Human Arginase 1 (rhArg1) in Patients With Advanced Arginine Auxotrophic Solid Tumors

This study is currently recruiting participants.
Verified September 2016 by Bio-Cancer Treatment International Limited
Sponsor:
ClinicalTrials.gov Identifier:
NCT02285101
First Posted: November 6, 2014
Last Update Posted: July 31, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Oncotherapeutics
Information provided by (Responsible Party):
Bio-Cancer Treatment International Limited
  Purpose
The goal of this clinical research study is to evaluate the safety of PEG-BCT- 100 given as an infusion to treat patients who bear advanced solid tumors that are dependent on arginine (melanoma, renal cell carcinoma, prostate cancer and hepatocellular carcinoma), and who have progressed after receiving approved or established therapies. This is a Phase 1 study; PEG-BCT-100 is an enzyme that degrades arginine and is an investigational drug.

Condition Intervention Phase
Hepatocellular Carcinoma Renal Cell Carcinoma Melanoma Prostate Adenocarcinoma Biological: PEG-BCT-100 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Recombinant Human Arginase 1 (rhArg1) in Patients With Advanced Arginine Auxotrophic Solid Tumors: Dose Escalation, Safety and PK/PD

Resource links provided by NLM:


Further study details as provided by Bio-Cancer Treatment International Limited:

Primary Outcome Measures:
  • Number of patients undergoing adverse events (AEs) or serious adverse events (SAEs) [ Time Frame: at least 13 weeks ]
  • Optimal Biological Dose [ Time Frame: 13 weeks ]
    The optimal biological dose (OBD) of PEG-BCT-100 will be calculated based on the pharmacodynamics (PD) endpoint of plasma arginine depletion relative to plasma pharmacokinetics (PK) of PEG-BCT-100


Secondary Outcome Measures:
  • Maximum Tolerated Dose and Dosing Schedule [ Time Frame: 4 weeks of treatment ]
  • Overall response [ Time Frame: 13 weeks ]
    Evaluate objective tumor responses by RECIST (Response Evaluation Criteria In Solid Tumors)

  • Pharmacokinetics (PK)-PEG-BCT-100 concentration [ Time Frame: 13 weeks ]
    Determine the dose-related peak to trough concentrations of plasma PEG-BCT-100 over time

  • Pharmacodynamics (PD) [ Time Frame: 13 weeks ]
    To determine the magnitude of plasma arginine depletion (AD) relative to the dose of PEG-BCT-100

  • PK-PEG-BCT-100 plasma clearance [ Time Frame: 13 weeks ]
    the plasma clearance of PEG-BCT-100

  • PD-duration of AD [ Time Frame: 13 weeks ]
    the time and duration of effective AD assessed by plasma arginine <8 µM relative to the plasma peak and time to clearance over the range of PEG-BCT-100 doses

  • PD-relationship between AD and PEG-BCT-100 dose [ Time Frame: 13 weeks ]
    the temporal and quantitative relationships of depleted plasma arginine to dose and plasma concentrations of PEG-BCT-100

  • PD-relationship between PEG-BCT-100 dose and tumor markers [ Time Frame: 13 weeks ]
    the temporal and quantitative relationships of depleted plasma arginine to dose and plasma concentrations of PEG-BCT-100; and, The relationship of PEG-BCT-100 dose and its resultant effective AD to changes in AFP/PSA and/or tumor symptoms and measurements.


Estimated Enrollment: 36
Study Start Date: November 2014
Estimated Study Completion Date: July 2019
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
PEG-BCT-100 at 0.5 mg/kg administered as a single dose on day 1 (week 1); if not DLTs are observed, PEG-BCT- 100 will be administered at 0.5 mg/kg on days 22 (week 4) and 29 (week 5). Patients responding to treatment or with stable disease may receive 8 additional weekly administrations of PEG-BCT-100 at 0.5 mg/kg. Beyond week 13, patients responding to treatment or with stable disease may continue to receive weekly PEG-BCT-100 at 0.5 mg/kg until disease progression at the discretion of the investigator.
Biological: PEG-BCT-100
Other Name: pegylated recombinant human arginase
Experimental: Cohort 2
PEG-BCT-100 at 1.0 mg/kg administered as a single dose on day 1 (week 1); if not DLTs are observed, PEG-BCT- 100 will be administered at 1.0 mg/kg on days 22 (week4) and 29 (week 5). Patients responding to treatment or with stable disease may receive 8 additional weekly administrations of PEG-BCT-100 at 1.0 mg/kg. Beyond week 13, patients responding to treatment or with stable disease may continue to receive weekly PEG-BCT-100 at 1.0 mg/kg until disease progression at the discretion of the investigator.
Biological: PEG-BCT-100
Other Name: pegylated recombinant human arginase
Experimental: Cohort 3
PEG-BCT-100 at 1.7 mg/kg administered as a single dose on day 1 (week 1); if not DLTs are observed, PEG-BCT- 100 will be administered at 1.7 mg/kg on days 22 (week 4) and 29 (week 5). Patients responding to treatment or with stable disease may receive 8 additional weekly administrations of PEG-BCT-100 at 1.7 mg/kg. Beyond week 13, patients responding to treatment or with stable disease may continue to receive weekly PEG-BCT-100 at 1.7 mg/kg until disease progression at the discretion of the investigator.
Biological: PEG-BCT-100
Other Name: pegylated recombinant human arginase
Experimental: Cohort 4
PEG-BCT-100 at 1.7 mg/kg administered as a single dose on day 1 (week 1); if not DLTs are observed, PEG-BCT- 100 will be administered at 2.7 mg/kg on days 22 (week 4) and 29 (week 5). Patients responding to treatment or with stable disease may receive 8 additional weekly administrations of PEG-BCT-100 at 2.7 mg/kg. Beyond week 13, patients responding to treatment or with stable disease may continue to receive weekly PEG-BCT-100 at 2.7 mg/kg until disease progression at the discretion of the investigator.
Biological: PEG-BCT-100
Other Name: pegylated recombinant human arginase
Experimental: Cohort 5
PEG-BCT-100 at 1.7 mg/kg administered as a single dose on day 1 (week 1); if not DLTs are observed, PEG-BCT- 100 will be administered at 4.0 mg/kg on days 22 (week 4) and 29 (week 5). Patients responding to treatment or with stable disease may receive 8 additional weekly administrations of PEG-BCT-100 at 4.0 mg/kg. Beyond week 13, patients responding to treatment or with stable disease may continue to receive weekly PEG-BCT-100 at 4.0 mg/kg until disease progression at the discretion of the investigator.
Biological: PEG-BCT-100
Other Name: pegylated recombinant human arginase
Experimental: Cohort 6
PEG-BCT-100 at a dose to be determined administered as a single dose on day 1 (week 1); if not DLTs are observed, PEG-BCT-100 will be administered at at a dose to be determined on days 22 (week 4) and 29 (week 5). Patients responding to treatment or with stable disease may receive 8 additional weekly administrations of PEG-BCT-100 at at a dose to be determined. Beyond week 13, patients responding to treatment or with stable disease may continue to receive weekly PEG-BCT-100 at at a dose to be determined until disease progression at the discretion of the investigator.
Biological: PEG-BCT-100
Other Name: pegylated recombinant human arginase

Detailed Description:
This is a phase 1, single site, open label and non-randomized study to evaluate the safety of PEG-BCT-100. Patient enrollment and sample size will follow a classical 3 + 3 dose-escalation design. The study will enroll a maximum of 36 patients. Cohorts of 3 patients will receive an initial single dose of PEG-BCT-100 beginning at 0.5 mg/kg. Single dose safety parameters including hematology and chemistry laboratory profiles will be monitored for 3 weeks. Patients not demonstrating a dose-limiting toxicity (DLT) following the single dose may then receive two additional doses of PEG-BCT-100 at the same dose level on Day 22 and Day 29. After these 2 additional doses, patients will undergo a full tumor and safety assessment after Day 29. Patients whose cancer is stable or responding may then receive weekly doses of PEG-BCT- 100 until disease progression. Dose escalations are planned for the next cohorts of 3 patients, which will be enrolled after Day 22 of the previous cohort, assuming that no single dose DLTs were reported. Each cohort of 3 patients may begin weekly administration if there is no DLTs by Day 22, and if the previous and lower dose cohort has successfully passed Week 4 of the study (doses on Days 1, and 22 + one week).
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of one of four advanced solid tumors: HCC according to the European Association for the Study of the Liver (EASL) criteria (see Appendix 13.2). Stage IIIb/IV malignant melanoma, stage IV Renal cell carcinoma or castration resistant adenocarcinoma of prostate (CRPC).
  • Advanced cancer not candidate for treatment with modality or agents that are approved or have established efficacy. Candidates who cannot tolerate standard treatment or whose cancers have progressed on current standard of care.
  • Males or females 18 years-old and above.
  • Ability to understand and willingness to provide written informed consent;
  • Karnofsky performance status (see Appendix 13.3) of 80% or above and expected survival of more than 12 weeks.
  • Negative urine pregnancy test, if female, and willingness to use an effective method of contraception during the entire study period whether the patient is male or female.

Exclusion Criteria:

  • Has received cancer treatment, e.g. chemotherapy, targeted biologic or enzymes, either approved or investigational, within 4 weeks prior to the start of the PEG-BCT-100;
  • Advancing liver failure indicated by uncontrolled ascites, pleural effusions, or encephalopathy.
  • Child-Pugh score of B and C (see Appendix 13.4).
  • Significant hepatic, renal or bone marrow dysfunction indicated by: total bilirubin >2.0 mg/dL, evidence of bile duct obstruction, serum albumin <2.5 g/dL, serum ALT or AST >2.5 x upper limit of normal, serum creatinine ≥1.5 mg/dL, ANC ≥1.5 x 109/L, platelets <100 x 109/L, or INR >2.0.
  • Significant cardiac or pulmonary disease defined by New York Heart Association (NYHA) Class III or IV (see Appendix 13.5), left ventricular ejection fraction (LVEF) lower than institutional normal limits by echo or MUGA, history of myocardial infarction within the past 6 months, significant unstable arrhythmia or evidence of ischemia on ECG.
  • Pregnant or nursing women. NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Significant active infection including HIV requiring oral or parenteral anti-infective therapies.
  • Use of investigational drug(s) within 4 weeks of enrollment.
  • Prior treatment with arginine depleting agent.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02285101


Contacts
Contact: Carley Turner 310-623-1206 CTurner@oncotherapeutics.com
Contact: Adriana Balandran 424-204-0736 abalandran@oncotherapeutics.com

Locations
United States, California
California Cancer Associates for Research and Excellence, cCARE Recruiting
San Diego, California, United States, 92111
Contact: Alberto Bessudo, MD    760-634-2361      
Sponsors and Collaborators
Bio-Cancer Treatment International Limited
Oncotherapeutics
Investigators
Principal Investigator: Chien-Shing Chen, MD, PhD Loma Linda University Medical Center
Principal Investigator: Alberto Bessudo, MD California Cancer Associates For Research and Excellence, cCARE
  More Information

Responsible Party: Bio-Cancer Treatment International Limited
ClinicalTrials.gov Identifier: NCT02285101     History of Changes
Other Study ID Numbers: BCT-100-005
First Submitted: October 23, 2014
First Posted: November 6, 2014
Last Update Posted: July 31, 2017
Last Verified: September 2016

Keywords provided by Bio-Cancer Treatment International Limited:
arginine auxotrophic tumors
PEG-BCT-100
arginase

Additional relevant MeSH terms:
Carcinoma
Adenocarcinoma
Carcinoma, Hepatocellular
Carcinoma, Renal Cell
Prostatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Genital Neoplasms, Male
Genital Diseases, Male
Prostatic Diseases