Clinical Trials List
Protocol NumberPOLARIS2012-005
NCT Number(ClinicalTrials.gov Identfier)NCT01665183
Completed
2015-01-01 - 2016-11-30
Phase I
Terminated1
Phase 1 Trial of ADI-PEG 20 Plus Cisplatin in Patients With Metastatic Melanoma or Other Advanced Solid Malignancies
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Trial Applicant
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Sponsor
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Trial scale
Multi-Regional Multi-Center
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Update
2026/03/01
Investigators and Locations
Co-Principal Investigator
- Chia-Jui Yen Division of General Internal Medicine
- Yan-Shen Shan Division of General Internal Medicine
- 姜乃榕 Division of General Internal Medicine
- Hui-Jen Tsai Division of General Internal Medicine
- Nai-Jung Chiang Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Cutaneous Melanoma, Uveal Melanoma, Ovarian Carcinoma or Other Advanced Solid Tumors
Objectives
Main research purposes:
To evaluate the safety and tolerability of ADI-PEG 20 in combination with cisplatin in the treatment of metastatic melanoma or other advanced solid malignancies.
The main objectives of the maximum tolerated dose (MTD) expansion phase (recommended phase 2 trial dose [RP2D]) are:
- To determine preliminary estimates of efficacy of ADI-PEG20 plus Cisplatin in the treatment of metastatic melanoma, as measured by RECIST 1.1 standards. Other advanced solid malignancies that have shown antitumor activity may also be evaluated (2-3 tumor types will be identified after dose escalation is completed).
Secondary research purpose:
- Determination of the maximum tolerated dose (MTD) of ADI-PEG 20 and treatment with Cisplatin
- Determine progression free survival
- Determine overall survival
- Determining the pharmacodynamics of ADI-PEG 20 and treatment with Cisplatin (Pharmacodynamics)
- Determination of immunogenicity of drugs treated with ADI-PEG 20 and Cisplatin
Test Drug
ADI-PEG 20
Active Ingredient
NaPO4 and NaCl buffer solution of ADI-PEG 20
Dosage Form
injection
Dosage
11.5 ± 1.0
Endpoints
1. Main evaluation indicators:
The degree of tumor response rate of subjects at weeks 8, 16 and 24 was evaluated, and descriptive statistical analysis was used to sort out the number and proportion of subjects in each period.
2. Secondary evaluation indicators:
The Kaplan-Meier method will be used to comprehensively calculate the disease progression-free survival and overall survival of the subjects. Will provide, individual point estimates (25th, 50th and 75th percentiles) with 95% confidence intervals. Likewise, the time to receive treatment will also be determined.
The degree of tumor response rate of subjects at weeks 8, 16 and 24 was evaluated, and descriptive statistical analysis was used to sort out the number and proportion of subjects in each period.
2. Secondary evaluation indicators:
The Kaplan-Meier method will be used to comprehensively calculate the disease progression-free survival and overall survival of the subjects. Will provide, individual point estimates (25th, 50th and 75th percentiles) with 95% confidence intervals. Likewise, the time to receive treatment will also be determined.
Inclution Criteria
Inclusion Criteria:
1.Histologically confirmed diagnosis of advanced solid tumor (dose escalation component) or metastatic melanoma (uveal or cutaneous) (doses escalation and MTD expansion components) or platinum-resistant (tumor progression within a year after the completion of platinum-based therapy) ovarian carcinoma (high grade serous, endometrial or poorly differentiated endometrioid) or HCC that has failed treatment with sorafenib or did not tolerate sorafenib or refused sorafenib, or HCC with coexistent BCT that has or has not been treated with chemotherapy, or BCT that has or has not been treated with chemotherapy. For HCC and HCC with coexistent BCT, cirrhotic status of Child-Pugh grade A-B7 must be present. Child-Pugh status should be determined based on clinical findings and laboratory data during the screening period (Appendix C). Subjects on anti-coagulants are to receive 1 point for their INR status, as they are presumed to have a <1.7 baseline PT/INR.
2.Ovarian cancer, or HCC, or HCC with coexistent BCT, or BCT only tissue either from an archived specimen or from a new biopsy of sufficient amount and quality should be available for IHC determination of ASS status to be performed retrospectively for the ovarian cancer, or HCC, or HCC with coexistent BCT, or BCT only cohorts. Subjects with no tissue available would require a biopsy.
3.Unresectable disease or patient refused surgery.
4.Progressive disease if treated with chemotherapy, radiotherapy, surgery or immunotherapy. If prior radiation was given, the measurable disease should be outside the radiation port. Unequivocal progression of HCC/BTC lesions previously treated with catheter-based therapy including transarterial chemoembolization or radioembolization is allowed.
5.Measurable disease as assessed by RECIST 1.1 criteria (Appendix A).
6.Age ≥ 18 years.
7.ECOG performance status of 0 - 1.
8.No prior systemic therapy, immunotherapy, investigational agent, chemoembolization, radioembolization or radiation therapy within the last 4 weeks.
9.Fully recovered from any prior surgery and no major surgery within 4 weeks of initiating treatment, except for gamma knife which can take place within 2 weeks. Surgery for placement of vascular access devices is acceptable.
1.Histologically confirmed diagnosis of advanced solid tumor (dose escalation component) or metastatic melanoma (uveal or cutaneous) (doses escalation and MTD expansion components) or platinum-resistant (tumor progression within a year after the completion of platinum-based therapy) ovarian carcinoma (high grade serous, endometrial or poorly differentiated endometrioid) or HCC that has failed treatment with sorafenib or did not tolerate sorafenib or refused sorafenib, or HCC with coexistent BCT that has or has not been treated with chemotherapy, or BCT that has or has not been treated with chemotherapy. For HCC and HCC with coexistent BCT, cirrhotic status of Child-Pugh grade A-B7 must be present. Child-Pugh status should be determined based on clinical findings and laboratory data during the screening period (Appendix C). Subjects on anti-coagulants are to receive 1 point for their INR status, as they are presumed to have a <1.7 baseline PT/INR.
2.Ovarian cancer, or HCC, or HCC with coexistent BCT, or BCT only tissue either from an archived specimen or from a new biopsy of sufficient amount and quality should be available for IHC determination of ASS status to be performed retrospectively for the ovarian cancer, or HCC, or HCC with coexistent BCT, or BCT only cohorts. Subjects with no tissue available would require a biopsy.
3.Unresectable disease or patient refused surgery.
4.Progressive disease if treated with chemotherapy, radiotherapy, surgery or immunotherapy. If prior radiation was given, the measurable disease should be outside the radiation port. Unequivocal progression of HCC/BTC lesions previously treated with catheter-based therapy including transarterial chemoembolization or radioembolization is allowed.
5.Measurable disease as assessed by RECIST 1.1 criteria (Appendix A).
6.Age ≥ 18 years.
7.ECOG performance status of 0 - 1.
8.No prior systemic therapy, immunotherapy, investigational agent, chemoembolization, radioembolization or radiation therapy within the last 4 weeks.
9.Fully recovered from any prior surgery and no major surgery within 4 weeks of initiating treatment, except for gamma knife which can take place within 2 weeks. Surgery for placement of vascular access devices is acceptable.
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. For the HCC, HCC/BTC and BTC subgroups hepatitis C infection and hepatitis B infection if controlled with antiviral therapy are allowable.
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, social situations that would limit compliance with study requirements.
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 in the opinion of the investigator will not affect patient outcome in the setting of current cancer diagnosis.
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).
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, social situations that would limit compliance with study requirements.
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 in the opinion of the investigator will not affect patient outcome in the setting of current cancer diagnosis.
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).
The Estimated Number of Participants
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Taiwan
50 participants
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Global
150 participants
