Recruitment

Recruitment Status
Terminated
Estimated Enrollment
47

Inclusion Criteria

ASS1 deficiency (defined as ≤50% ASS expression) demonstrated on tissue specimen (cytospin samples are acceptable) by immunohistochemistry (IHC). For subjects previously treated with chemotherapy, this specimen may have been obtained before that chemotherapy. A new tissue specimen obtained after most recent chemotherapy is not required. Thus ASS1 deficiency is required for entrance into the study. If tissue is not available to determine ASS1 deficiency, then tissue must be obtained by biopsy to determine ASS1 status.
Measurable disease as assessed by modified RECIST for MPM and by RECIST 1.1 criteria for peritoneal mesothelioma, NSCLC, uveal melanoma, HCC, glioma and sarcomatoid carcinoma
ECOG performance status of 0 - 1
...
ASS1 deficiency (defined as ≤50% ASS expression) demonstrated on tissue specimen (cytospin samples are acceptable) by immunohistochemistry (IHC). For subjects previously treated with chemotherapy, this specimen may have been obtained before that chemotherapy. A new tissue specimen obtained after most recent chemotherapy is not required. Thus ASS1 deficiency is required for entrance into the study. If tissue is not available to determine ASS1 deficiency, then tissue must be obtained by biopsy to determine ASS1 status.
Measurable disease as assessed by modified RECIST for MPM and by RECIST 1.1 criteria for peritoneal mesothelioma, NSCLC, uveal melanoma, HCC, glioma and sarcomatoid carcinoma
ECOG performance status of 0 - 1
Predicted life expectancy of at least 12 weeks.
Histologically proven advanced MPM, advanced peritoneal mesothelioma (for dose escalation cohort only) or non-squamous NSCLC (stage IIIB/IV) who have not been treated with prior chemotherapy or immunotherapy, except that NSCLC subjects with EGFR mutant or ALK positive must have had an EGFR tyrosine kinase inhibitor (TKI) or ALK inhibitor and progressed or been shown to be intolerant of therapy prior to enrolling in this trial, if such ALK inhibitor and EGFR targeted therapy are approved and available in the country in which patients are being enrolled OR Histologically proven metastatic uveal melanoma who have not been treated with prior chemotherapy (MTD cohort only), OR Histologically proven HCC who have failed (PD and/or side effects-been intolerant of) treatment with sorafenib. Failure is defined as having progressed radiographically on, or been intolerant to prior systemic therapy. Intolerance is defined as discontinuation due to an AE(s) on prior systemic therapy that was unacceptable to the treating physician and / or patient, with or without dose interruption and modification. Failure requires at least 14 days of treatment with sorafenib, except for a subject that has had a severe allergic reaction to sorafenib at any time, even less than 14 days of treatment with sorafenib and thus it would be imprudent to re-challenge them with that agent. 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 E). 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.", OR Histologically proven high-grade glioma who have failed (PD and/or side effects) treatment with radiotherapy ± temozolomide, OR Sarcomatoid cancer of any line.

Exclusion Criteria

Symptomatic brain or spinal cord metastases (patients must be stable for > 3 months post radiotherapy or surgery) for subjects with mesothelioma, NSCLC, uveal melanoma excludes subjects with HCC or glioma).
Serious infection requiring treatment with intravenous antibiotics at the time of study entrance, or an infection requiring intravenous therapy within 7 days prior to the first dose of study treatment.
Major thoracic or abdominal surgery from which the patient has not yet recovered.
...
Symptomatic brain or spinal cord metastases (patients must be stable for > 3 months post radiotherapy or surgery) for subjects with mesothelioma, NSCLC, uveal melanoma excludes subjects with HCC or glioma).
Serious infection requiring treatment with intravenous antibiotics at the time of study entrance, or an infection requiring intravenous therapy within 7 days prior to the first dose of study treatment.
Major thoracic or abdominal surgery from which the patient has not yet recovered.
Radiotherapy (except for palliative reasons), targeted therapy, or immunotherapy (except for uveal melanoma) the previous four weeks before study treatment.
Ongoing toxic manifestations of previous treatments.

Summary

Conditions
  • Glioma
  • Hepatocellular Carcinoma
  • Non-squamous Non-small Cell Lung Carcinoma
  • Peritoneal Mesothelioma Malignant Advanced
  • Pleural Mesothelioma Malignant Advanced
  • Sarcomatoid Carcinoma
  • Uveal Melanoma
Type
Interventional
Phase
Phase 1
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

Description

Weekly ADI-PEG 20 will be cohort dose escalated (18, 27 and 36 mg/m2), with pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 both given every 3 weeks. Subjects may receive a maximum of 6, 3-week cycles of ADIPemCis for a total of 18 weeks of treatment. Subjects with NSCLC may receive 4 to 6, 3-week cycle...

Weekly ADI-PEG 20 will be cohort dose escalated (18, 27 and 36 mg/m2), with pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 both given every 3 weeks. Subjects may receive a maximum of 6, 3-week cycles of ADIPemCis for a total of 18 weeks of treatment. Subjects with NSCLC may receive 4 to 6, 3-week cycles as per local institutional policy. Those subjects completing ADIPemCis treatment may continue on ADI-PEG 20 monotherapy if they have SD or better. Subjects with NSCLC may continue to receive pemetrexed as per local institutional policy along with ADI-PEG 20 and/or continue on ADI-PEG 20 monotherapy after pemetrexed is also discontinued.

Inclusion Criteria

ASS1 deficiency (defined as ≤50% ASS expression) demonstrated on tissue specimen (cytospin samples are acceptable) by immunohistochemistry (IHC). For subjects previously treated with chemotherapy, this specimen may have been obtained before that chemotherapy. A new tissue specimen obtained after most recent chemotherapy is not required. Thus ASS1 deficiency is required for entrance into the study. If tissue is not available to determine ASS1 deficiency, then tissue must be obtained by biopsy to determine ASS1 status.
Measurable disease as assessed by modified RECIST for MPM and by RECIST 1.1 criteria for peritoneal mesothelioma, NSCLC, uveal melanoma, HCC, glioma and sarcomatoid carcinoma
ECOG performance status of 0 - 1
...
ASS1 deficiency (defined as ≤50% ASS expression) demonstrated on tissue specimen (cytospin samples are acceptable) by immunohistochemistry (IHC). For subjects previously treated with chemotherapy, this specimen may have been obtained before that chemotherapy. A new tissue specimen obtained after most recent chemotherapy is not required. Thus ASS1 deficiency is required for entrance into the study. If tissue is not available to determine ASS1 deficiency, then tissue must be obtained by biopsy to determine ASS1 status.
Measurable disease as assessed by modified RECIST for MPM and by RECIST 1.1 criteria for peritoneal mesothelioma, NSCLC, uveal melanoma, HCC, glioma and sarcomatoid carcinoma
ECOG performance status of 0 - 1
Predicted life expectancy of at least 12 weeks.
Histologically proven advanced MPM, advanced peritoneal mesothelioma (for dose escalation cohort only) or non-squamous NSCLC (stage IIIB/IV) who have not been treated with prior chemotherapy or immunotherapy, except that NSCLC subjects with EGFR mutant or ALK positive must have had an EGFR tyrosine kinase inhibitor (TKI) or ALK inhibitor and progressed or been shown to be intolerant of therapy prior to enrolling in this trial, if such ALK inhibitor and EGFR targeted therapy are approved and available in the country in which patients are being enrolled OR Histologically proven metastatic uveal melanoma who have not been treated with prior chemotherapy (MTD cohort only), OR Histologically proven HCC who have failed (PD and/or side effects-been intolerant of) treatment with sorafenib. Failure is defined as having progressed radiographically on, or been intolerant to prior systemic therapy. Intolerance is defined as discontinuation due to an AE(s) on prior systemic therapy that was unacceptable to the treating physician and / or patient, with or without dose interruption and modification. Failure requires at least 14 days of treatment with sorafenib, except for a subject that has had a severe allergic reaction to sorafenib at any time, even less than 14 days of treatment with sorafenib and thus it would be imprudent to re-challenge them with that agent. 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 E). 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.", OR Histologically proven high-grade glioma who have failed (PD and/or side effects) treatment with radiotherapy ± temozolomide, OR Sarcomatoid cancer of any line.

Exclusion Criteria

Symptomatic brain or spinal cord metastases (patients must be stable for > 3 months post radiotherapy or surgery) for subjects with mesothelioma, NSCLC, uveal melanoma excludes subjects with HCC or glioma).
Serious infection requiring treatment with intravenous antibiotics at the time of study entrance, or an infection requiring intravenous therapy within 7 days prior to the first dose of study treatment.
Major thoracic or abdominal surgery from which the patient has not yet recovered.
...
Symptomatic brain or spinal cord metastases (patients must be stable for > 3 months post radiotherapy or surgery) for subjects with mesothelioma, NSCLC, uveal melanoma excludes subjects with HCC or glioma).
Serious infection requiring treatment with intravenous antibiotics at the time of study entrance, or an infection requiring intravenous therapy within 7 days prior to the first dose of study treatment.
Major thoracic or abdominal surgery from which the patient has not yet recovered.
Radiotherapy (except for palliative reasons), targeted therapy, or immunotherapy (except for uveal melanoma) the previous four weeks before study treatment.
Ongoing toxic manifestations of previous treatments.

Tracking Information

NCT #
NCT02029690
Collaborators
Not Provided
Investigators
  • Principal Investigator: Peter Szlosarek, MD, PhD Barts Cancer Institute
  • Peter Szlosarek, MD, PhD Barts Cancer Institute
About Us
Innovation
Privacy
Terms
Copyright
Get Well Soon © Copyright 2024