Clinical trial NCT02722369: STUDY 15 - Comparing Gemcitabine/Carboplatin and Hydroxychloroquine Versus Carboplatin/Etoposide Therapy Alone in Small Cell Lung Cancer (SCLC)
Official title: A Phase II, Multicentre, Randomised Trial Comparing Combination Gemcitabine/Carboplatin and Hydroxychloroquine Versus Carboplatin/Etoposide Therapy Alone in Small Cell Lung Cancer (SCLC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Small Cell Lung Cancer
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2016-03-30
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival
timeFrame: Defined as the time from randomisation to first progression/death (whichever came first), assessed up to 41 months
Secondary outcomes:
measure: Overall survival
timeFrame: From date of randomisation to death due to any cause, assessed up to 41 months
measure: Objective response as measured by Response Evaluation Criteria in Solid Tumours (RECIST) v.1.1
timeFrame: From first tumour assessment to progression/trial end (whichever is first), assessed up to 41 months
measure: Adverse events
timeFrame: From date of consent to 30 days after final trial treatment
measure: Quality of life as measured by EQ-5D
timeFrame: From baseline to progression/trial end (whichever is first), assessed up to 41 months
measure: Quality of life as measured by QLQC-30
timeFrame: From baseline to progression/trial end (whichever is first), assessed up to 41 months
measure: Quality of life as measured by QLQ-LC-13
timeFrame: From baseline to progression/trial end (whicenver is first), assessed up to 41 months
measure: Compliance measured by dose intensity
timeFrame: From first date of trial treatment to progression/trial end (whichever is first), assessed up to 41 months
measure: Compliance measured by dose exposure
timeFrame: From first date of trial treatment to progression/trial end (whichever is first), assessed up to 41 months
Other outcomes:
Locations:
city: Dorchester
country: United Kingdom
facility: Dorset County Hospital NHS Foundation Trust
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: Harlow
country: United Kingdom
facility: The Princess Alexandra Hospital NHS Trust
city: Lancaster
country: United Kingdom
facility: University Hospitals of Morecambe Bay NHS Foundation Trust
city: Leicester
country: United Kingdom
facility: University Hospital Leicester NHS Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: UCLH
city: Manchester
country: United Kingdom
facility: The Christie
city: Northwood
country: United Kingdom
facility: East and North Herts NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Peterborough
country: United Kingdom
facility: North West Anglia NHS Trust
city: Rhyl
country: United Kingdom
facility: Betsi Cadwaladr University Health Board
city: Steeton
country: United Kingdom
facility: Airedale NHS Foundation Trust
Study officials:
References: