E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patient with advanced non-small cell lung cancer receiving treatment with carboplatin-pemetrexed-pembrolizumab. |
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E.1.1.1 | Medical condition in easily understood language |
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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 investigate the effect of fluid infusion to prevent deterioration of kidney function due to pemetrexed, during treatment with carboplatin, pemetrexed and pembrolizumab in patients with non-squamous NSCLC. The primary objective is to reduce the incidence of acute kidney disease (AKD) from 30 to 10%. |
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E.2.2 | Secondary objectives of the trial |
Secundary objective is to prevent the development of chronic kidney disease (CKD). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants are eligible to be included in the study if the following criteria apply: • Age > 18 years • Patient must be willing and capable of giving written Informed Consent, and meeting all study requirements • Subjects with advanced stage non-squamous cell lung cancer, receiving first line treatment with induction carboplatinum / pemetrexed / pembrolizumab and subsequently pemetrexed / pembrolizumab maintenance therapy. • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 • Adequate haematological, renal and liver function 1. Adequate hematological function: • Hemoglobin ≥90 g/L or ≥5.6 mmol/L • WBC ≥1.0× 109/L • Lymphocytes ≥0.5 g/L • Absolute neutrophil count (ANC) ≥1.5× 109/L • Platelet count ≥100× 109/L 2. Renal function: • Calculated creatinine clearance ≥45 mL/min (according to Cockcroft- Gault) 3. Adequate liver function: • ALT and AST ≤2.5× ULN. If the patient has liver metastases, ALT and AST must be ≤5× ULN • Total serum bilirubin ≤1.5× ULN. If the patient has liver metastases or documented Gilbert’s syndrome (unconjugated hyperbilirubinemia) ≤3× ULN. |
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E.4 | Principal exclusion criteria |
Patients should not enter the study if any of the following exclusion criteria are fulfilled: • Subject with an active auto-immune disease requiring systemic treatment • Lung disease requiring systemic steroids in doses of >10 mg prednisolone (or equivalent dose of another steroid) • Previous allogeneic or organ transplant • Known heart failure • Myocardial infarction previous 6 months • Serious concomitant systemic disorders (for example active infection, unstable cardiovascular disease) which in the opinion of the investigator would compromise the patient's ability to complete the study, or would interfere with the evaluation of the efficacy and safety of the study treatment • Known positive test for hepatitis B virus or hepatitis C virus or human immunodeficiency virus (HIV) indicating acute or chronic infection • Moderate to severe hypercalcemia, i.e. total calcium level corrected for albumin ≥12.0 mg/dL (3.0 mmol/L) • Simultaneous participation in other clinical trial • Pregnant or lactating women |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is a decrease kidney function defined as: • eGFR < 45 mL.min-1 per 1.73m2 • increase in serum creatinine >50% compared to baseline.
The study will end after 8 cycles of treatment including 4 cycles of carboplatin / pemetrexed / pembrolizumab (induction) and 4 cycles of pemetrexed / pembrolizumab (maintenance); or when the primary endpoints are met. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary end points are: • Time to reach primary endpoints • Rate of decline in kidney function (eGFR and creatinine) • Treatment dose intensity, including number of dose reductions |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every three weeks. Maximum of 24 weeks. |
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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 | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
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
| 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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |