Recombinant Human Arginase 1 (rhArg1) in Patients With Advanced Arginine Auxotrophic Solid Tumors
1 other identifier
interventional
23
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Nov 2014
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 23, 2014
CompletedStudy Start
First participant enrolled
November 1, 2014
CompletedFirst Posted
Study publicly available on registry
November 6, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2019
CompletedApril 24, 2020
April 1, 2020
4.3 years
October 23, 2014
April 22, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of patients undergoing adverse events (AEs) or serious adverse events (SAEs)
at least 13 weeks
Optimal Biological Dose
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
13 weeks
Secondary Outcomes (8)
Maximum Tolerated Dose and Dosing Schedule
4 weeks of treatment
Overall response
13 weeks
Pharmacokinetics (PK)-PEG-BCT-100 concentration
13 weeks
Pharmacodynamics (PD)
13 weeks
PK-PEG-BCT-100 plasma clearance
13 weeks
- +3 more secondary outcomes
Study Arms (6)
Cohort 1
EXPERIMENTALPEG-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.
Cohort 2
EXPERIMENTALPEG-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.
Cohort 3
EXPERIMENTALPEG-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.
Cohort 4
EXPERIMENTALPEG-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.
Cohort 5
EXPERIMENTALPEG-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.
Cohort 6
EXPERIMENTALPEG-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.
Interventions
Eligibility Criteria
You may qualify if:
- Confirmed diagnosis of Stage IIIb/IV malignant melanoma 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bio-Cancer Treatment International Limitedlead
- Oncotherapeuticscollaborator
Study Sites (2)
California Cancer Associates for Research and Excellence, cCARE
San Diego, California, 92111, United States
John Wayne Cancer Institute
Santa Monica, California, 90404, United States
Related Publications (1)
De Santo C, Cheng P, Beggs A, Egan S, Bessudo A, Mussai F. Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma. J Hematol Oncol. 2018 May 18;11(1):68. doi: 10.1186/s13045-018-0612-6.
PMID: 29776373DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Alberto Bessudo, MD
California Cancer Associates For Research and Excellence, cCARE
- PRINCIPAL INVESTIGATOR
Steven O'Day, MD
Saint John's Cancer Institute
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 23, 2014
First Posted
November 6, 2014
Study Start
November 1, 2014
Primary Completion
February 1, 2019
Study Completion
February 1, 2019
Last Updated
April 24, 2020
Record last verified: 2020-04