E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine whether treatment with ADI-PEG 20 will shrink small cell lung cancer. |
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E.2.2 | Secondary objectives of the trial |
To further determine the safety profile of ADI-PEG 20, evaluate blood levels of amino acid arginine which are important for tumour growth, measure immunogenicity (antibodies) to ADI-PEG 20 and life span after receiving ADI-PEG 20 treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1)Patients must have histologically documented small cell lung cancer (SCLC) • Sensitive disease patients who maintain an appropriate response to 1st line chemotherapy for 3 months or more (Group 1) or • Refractory disease patients who either had no response to 1st line chemotherapy, or progressed within 3 months after completing 1st line chemotherapy treatment (Group 2) or • Patients (sensitive or refractory) who have completed or failed 2nd line chemotherapy (Group 2) 2)Measurable disease using RECIST criteria. 3)ASS tumour expression must be either negative or <5% + tumor cells (by IHC analysis) 4)Karnofsky performance status of 60% or more. 5)Laboratory parameters for vital functions should be in the normal range. Laboratory abnormalities that are not clinically significant are generally permitted, except for the following laboratory parameters, which must be within the ranges specified: Neutrophil count ≥ 1.5 x 109/L Lymphocyte count ≥ 0.5 x 109/L Platelet count ≥ 50 x 109/L Serum creatinine ≤ 1.5 ULN (or CrCl ≥60mL/min) Serum bilirubin ≤ 2mg/dL (or ≤34 µmol/L) Serum uric acid ≤ 8mg/dL (or ≤ 0.48 mmol/L) 6)Age ≥18 years. 7)Able and willing to give valid written informed consent |
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E.4 | Principal exclusion criteria |
1)Subjects previously treated with ADI-PEG 20. 2)Known allergy to pegylated products. 3)History of uncontrolled seizure. 4)Serious illnesses e.g. serious infections requiring antibiotics, bleeding disorders, or any condition that in the opinion of the Investigator would interfere with the ability of the patient to fulfill the study requirements. 5)Metastatic disease to the central nervous system, unless treated and stable. 6)Known immunodeficiency or HIV positivity. 7)Participation in any other clinical trial involving another investigational agent within 3 weeks prior to first dosing of study agent. 8)Any other malignancy that requires concomitant therapy that is restricted as per protocol. 9)Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study. 10)Lack of availability for clinical follow-up assessment. 11)Pregnancy or breast feeding. 12)Refusal or inability to use effective means of contraception for men and women of childbearing potential for the duration of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Tumour Response by RECIST criteria. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients are fully evaluable for the primary endpoint of tumour response if they hav: - received at least two scheduled doses of study drug during the first 2 weeks on a consecutive basis. - had baseline and at least one post-baseline tumour response assessment - had no major eligibility or protocol violations |
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E.5.2 | Secondary end point(s) |
The secondary endpoints of the trial are as follows: 1)Safety and Tolerability (laboratory tests, vital signs, physical exams and patient interviews will be performed to detect new abnormalities and deterioration of any pre-existing conditions) 2) Pharmacodynamics (plasma arginine and citrulline amino acid levels will be determined weekly in cycle 1-2 and every 4 weeks in cycle 3-4 to detect changes associated with ADI-PEG 20 treatment) 3) Immunogenicity (peripheral blood ADI-PEG 20 antibodies will be determined weekly in cycle 1-2 and every 4 weeks in cycle 3-4) 4) Overall Survival (measured from initial date of treatment to the recorded date of death) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Safety and Tolerability (Duration of trial treatment) 2) Pharmacodynamics (Weekly in cycle 1-2, every 4 weeks in cycle 3-4) 3) Immunogenicity (Weekly in cycle 1-2 and every 4 weeks in cycle 3-4) 4) Overall survival (measured from initial date of treatment to the recorded date of death) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 24 |