STUDY 15 - Comparing Gemcitabine/Carboplatin and Hydroxychloroquine Versus Carboplatin/Etoposide Therapy Alone in Small Cell Lung Cancer (SCLC)

University College London (UCL)

Status and phase: Terminated; Phase 2

Conditions: Small Cell Lung Cancer

Treatments: Drug: Carboplatin; Drug: Gemcitabine; Drug: Hydroxychloroquine; Drug: Etoposide

Study type: Interventional

Funder types: Other

Identifiers

NCT02722369

UCL/12/0515

Details and patient eligibility

About

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)

Full 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.

Enrollment: 72 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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72 participants in 2 patient groups

Control Arm

Active Comparator group

Description:

* IV carboplatin AUC5 (area under curve) on Day1 * IV etoposide 120mg/m2 Day 1, followed by oral etoposide 100mg BD (twice daily) on Day 2 and Day 3

Treatment:

Drug: Etoposide

Drug: Carboplatin

Investigational Arm

Experimental group

Description:

* IV gemcitabine 1200mg/m2 on Day 1 and Day 8 * IV carboplatin AUC5 on Day 1 * Oral HCQ will be taken at a dose of 400mg BD from day 1 of cycle 1 (maximum of 30 months)

Treatment:

Drug: Hydroxychloroquine

Drug: Gemcitabine

Drug: Carboplatin