E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Lung adenocarcinoma chemotherapy naive or recurrent for which vinorelbine/cisplatin would be appropriate therapy |
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E.1.1.1 | Medical condition in easily understood language |
Lung adenocarcinoma not treated yet or recurrent after treatment for which vinorelbine/cisplatin would be appropriate therapy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025031 |
E.1.2 | Term | Lung adenocarcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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: • Safety and tolerability of L-DOS47 in combination treatment with vinorelbine/cisplatin • Dose limiting toxicities (DLTs) of L-DOS47 in combination treatment with vinorelbine/cisplatin • Maximum tolerated dose (MTD) and recommended Part 2 dose of L-DOS47 in combination treatment with vinorelbine/cisplatin • Preliminary efficacy of L-DOS47 by comparing the time to disease progression (TTP) of L-DOS47 in combination with vinorelbine/cisplatin to vinorelbine/cisplatin alone in patients with lung adenocarcinoma |
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E.2.2 | Secondary objectives of the trial |
• Determine the preliminary efficacy of L-DOS47 by comparing the objective response rate (ORR) of L-DOS47 in combination with vinorelbine/cisplatin to vinorelbine/cisplatin alone in patients with lung adenocarcinoma (Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1 criteria will be used to determine the objective response rate.) • Compare the safety and tolerability of L-DOS47 in combination with vinorelbine/cisplatin to vinorelbine/cisplatin alone in patients with lung adenocarcinoma • Compare the overall survival (OS) of patients administered L-DOS47 in combination with vinorelbine/cisplatin to patients administered vinorelbine/cisplatin alone |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female aged ≥ 18 years old 2. Histologically confirmed lung adenocarcinoma, classified as: - Chemotherapy-naive patients with metastatic lung adenocarcinoma for whom vinorelbine/cisplatin would be appropriate therapy; - Metastatic recurrent lung adenocarcinoma following prior surgery, radiation and/or adjuvant chemotherapy at least 6 months ago, for whom vinorelbine/cisplatin would be appropriate therapy; - Staging must be assessed according to TNM, 8th edition and based on computed tomography (CT) scan; - Grade 1 – 4 adenocarcinoma. 3. No prior adjuvant chemotherapy within 6 months of the first treatment day if there is recurrent disease 4. At least a single measurable lesion in accordance with the RECIST v1.1 criteria 5. Eastern Cooperative Oncology Group (ECOG) performance status: 0-1 6. A life expectancy of ≥ 3 months 7. Adequate organ function as determined by the following criteria: - Absolute neutrophil count (ANC) ≥ 1.5 × 109/L - Platelet count ≥ 100 × 109/L - Haemoglobin (HGB) ≥ 9 g/dL - Creatinine clearance ≥ 60 mL/min calculated using the Cockcroft-Gault Formula and serum creatinine ≤ 1.5 × the upper limit of normal (ULN) - Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 3 × ULN or < 5 × ULN if liver abnormalities are due to underlying malignancy - Total bilirubin ≤ 1.5 × ULN Note: Blood transfusions administered for the sole purpose of meeting the study inclusion criteria between the time informed consent is signed and first dose of L-DOS47 is administered are not allowed. 8. Able to understand the information provided to them and to give written informed consent before any study activities are conducted 9. Willing and able to comply with scheduled visits, treatment plans, laboratory tests and other study procedures 10. Not pregnant and do not plan to become pregnant during the study. Females of childbearing potential must provide a negative pregnancy test within the Screening period (Day -21 to 0) and agree to use adequate non- hormonal contraception (which includes but is not limited to double barrier or sexual abstinence) during the study and for a period of 90 days following the last dose of study treatment. Male patients and their female partners of child-bearing potential must agree to each use an approved form of contraception (which includes but is not limited to double barrier or sexual abstinence) during the study and for a period of 90 days following the last dose of study treatment. |
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E.4 | Principal exclusion criteria |
1. Pregnant or nursing mother 2. Prior history of other malignancies with the exception of non-melanoma skin cancer 3. Patients with a known positive Epidermal Growth Factor Receptor (EGFR) mutation or whose tumour harbour an anaplastic lymphoma kinase (ALK) translocation 4. Active central nervous system metastasis and/or leptomeningeal disease (known or suspected); Patients with asymptomatic brain metastases are eligible if they had local therapy more than 1 month before enrolment 5. Evidence of active infection 6. Received treatment in another clinical study within the 30 days before commencing study drug and have not recovered from side effects of a study drug, except for alopecia 7. A serious uncontrolled medical condition 8. Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen, or hepatitis C positive 9. Sustained QT interval corrected for heart rate (QTc) with Fridericia’s correction > 450 msec at Screening, or a history of additional risk factors for Torsades de pointes (e.g., heart failure, hypokalaemia, family history of long QT syndrome) 10. Pre-existing peripheral neuropathy Grade ≥1 CTCAE (v. 4.03) 11. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent or compliance with the requirements of the protocol 12. Received chemotherapy during the 30 days before study treatment start; are receiving radiotherapy, targeted therapy, hormonal therapy, immunotherapy, major surgery or other study drugs during the 4 weeks before study treatment start, and have not recovered from all treatment related toxicities to Grade ≤ 1, except for alopecia. (Radiotherapy is allowed for the symptomatic treatment of bone metastases.) 13. Taking systemic steroids (other than inhalers or topical steroids) or other medication to suppress the immune system 14. Participating (or planning to participate) in any other clinical trial during this study |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is time to disease progression. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time to disease progression will be analysed using Kaplan-Meier survival estimates. Follow-up for disease progression will be conducted by radiologic assessments every 6 weeks (± 7 days) until one of the following occurs: disease progression, patient initiates non-study cancer treatment, patient withdraws consent, or becomes lost-to-follow-up;
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E.5.2 | Secondary end point(s) |
Secondary endpoints include: • Objective response as measured using RECIST defined as the proportion of patients with a best overall response of complete response and partial response • Overall survival • Safety and tolerability of L-DOS47 in combination with vinorelbine/cisplatin
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Follow-up for disease progression will be conducted by radiologic assessments every 6 weeks (± 7 days) until one of the following occurs: disease progression, patient initiates non-study cancer treatment, patient withdraws consent, or becomes lost-to-follow-up; Survival data will be captured by telephone call every 30 days (± 7 days) and patients will be followed until 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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
tolerability and immunogenicity |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
2 phases: dose escalation and randomised treatment |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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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End of study is defined as the last patient that progresses in either study arm. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |