Small Cell Lung Cancer
Conditions
Brief summary
To determine whether the combination of gemcitabine/carboplatin with hydroxychloroquine (HCQ) is associated with an improved clinical outcome (progression free and overall survival) compared with chemotherapy alone in patients with small cell lung cancer (SCLC)
Detailed description
This is a multicentre, randomised, phase II trial which aims to compare the combination of hydroxychloroquine and gemcitabine/carboplatin versus standard carboplatin/etoposide chemotherapy, as first line treat in patients with stage IV disease. The standard first line chemotherapy treatment remains a platinum-based chemotherapy and this has been unchanged for 20 years. Novel active treatment approaches are urgently needed to improve survival in SCLC. Patients are randomised to one of two treatment arms; carboplatin/etoposide or gemcitabine/carboplatin/hydroxychloroquine.
Interventions
DRUGGemcitabine
Chemotherapy
DRUGCarboplatin
Chemotherapy
DRUGEtoposide
Chemotherapy
DRUGHydroxychloroquine
Maintenance Agent
Sponsors
University College, London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed SCLC * Stage IV disease * Performance status ECOG 0-2 * Life expectancy \>8 weeks * Age 18 or over * Willing and able to give informed consent * Patient considered able to tolerate chemotherapy * Adequate renal function - defined by GFR ≥50mL/min as measured by EDTA or C&G * Adequate bone marrow reserve: Absolute neutrophil count ≥1.5 x 109/L, haemoglobin ≥90 g/L, platelet count ≥100 x 109/L * Negative pregnancy test for WCBP * Highly effective contraception is mandatory for all patients of reproductive potential * At least one site of measurable disease (target lesion) for RECIST 1.1 evaluation * Hypersensitivity or history of severe allergic reaction to any of the IMPs * Able to swallow medication
Exclusion criteria
* Mixed cell histology (i.e. NSCLC and SCLC) * Prior macular degeneration or diabetic retinopathy * History of glaucoma * Patients with abnormal LFTs (ALP, ALT/AST\*) that are ≥3 x ULN (≥5 x ULN for patients with liver metastases) * Patients with abnormal bilirubin levels that are ≥1.5 x ULN * Prior treatment for this disease e.g. chemotherapy, surgery, radiotherapy (except palliative radiotherapy to bone metastases) * Documented side effects to chloroquine or related agents * Treatment with chloroquine or related agents within the last year prior to randomisation * Evidence of significant medical condition or laboratory finding which, in the opinion of the investigator, makes it undesirable for the patient to participate in the trial * Previous medical history of prolonged QT interval * A history of prior malignant tumour, unless the patient has been without evidence of disease for at least 3 years or the tumour was a non-melanoma skin tumour or early cervical cancer * Patients with symptomatic brain metastases * Women who are breastfeeding * Concurrent cytochrome P450 enzyme-inducing anticonvulsant drugs e.g. phenytoin, carbamazepine, phenobarbital, primidone or oxcarbazepine * Patients who are unable to have their digoxin levels regularly monitored * if both ALT and AST performed then both need to be recorded
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression free survival | Defined as the time from randomisation to first progression/death (whichever came first), assessed up to 41 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response as measured by Response Evaluation Criteria in Solid Tumours (RECIST) v.1.1 | From first tumour assessment to progression/trial end (whichever is first), assessed up to 41 months | Complete Response (CR)/ Partial Response (PR)/ Progressive Disease (PD)/ Stable Disease (SD) |
| Adverse events | From date of consent to 30 days after final trial treatment | Including ophthalmologic and treatment specific toxicities |
| Quality of life as measured by EQ-5D | From baseline to progression/trial end (whichever is first), assessed up to 41 months | The questionnaire is a standardised questionnaire |
| Overall survival | From date of randomisation to death due to any cause, assessed up to 41 months | — |
| Quality of life as measured by QLQ-LC-13 | From baseline to progression/trial end (whicenver is first), assessed up to 41 months | The questionnaire is a standardised questionnaire |
| Compliance measured by dose intensity | From first date of trial treatment to progression/trial end (whichever is first), assessed up to 41 months | Capturing dose delays, modifications and omissions |
| Compliance measured by dose exposure | From first date of trial treatment to progression/trial end (whichever is first), assessed up to 41 months | Capturing dose delays, modifications and omissions |
| Quality of life as measured by QLQC-30 | From baseline to progression/trial end (whichever is first), assessed up to 41 months | The questionnaire is a standardised questionnaire |
Countries
United Kingdom
Outcome results
None listed