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

Sponsor

University College, London (Other)

Overall Status

Terminated

CT.gov ID

NCT02722369

Collaborator

(none)

Enrollment

Locations

Arms

47.9

Actual Duration (Months)

5.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Small Cell Lung Cancer	Drug: Gemcitabine Drug: Carboplatin Drug: Etoposide Drug: Hydroxychloroquine	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Mar 14, 2017

Actual Primary Completion Date :

Mar 12, 2021

Actual Study Completion Date :

Mar 12, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control Arm 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	Drug: Carboplatin Chemotherapy Drug: Etoposide Chemotherapy
Experimental: Investigational Arm 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)	Drug: Gemcitabine Chemotherapy Drug: Carboplatin Chemotherapy Drug: Hydroxychloroquine Maintenance Agent

Arm

Intervention/Treatment

Active Comparator: Control Arm

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

Drug: Carboplatin

Chemotherapy

Drug: Etoposide

Chemotherapy

Experimental: Investigational Arm

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)

Drug: Gemcitabine

Chemotherapy

Drug: Carboplatin

Chemotherapy

Drug: Hydroxychloroquine

Maintenance Agent

Outcome Measures

Primary Outcome Measures

Progression free survival [Defined as the time from randomisation to first progression/death (whichever came first), assessed up to 41 months]

Secondary Outcome Measures

Overall survival [From date of randomisation to death due to any cause, assessed up to 41 months]
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
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	Country
1	Dorset County Hospital NHS Foundation Trust	Dorchester	United Kingdom
2	Royal Surrey County Hospital	Guildford	United Kingdom
3	The Princess Alexandra Hospital NHS Trust	Harlow	United Kingdom
4	University Hospitals of Morecambe Bay NHS Foundation Trust	Lancaster	United Kingdom
5	University Hospital Leicester NHS Trust	Leicester	United Kingdom
6	Guy's and St Thomas' Hospitals NHS Foundation Trust	London	United Kingdom
7	UCLH	London	United Kingdom
8	The Christie	Manchester	United Kingdom
9	East and North Herts NHS Foundation Trust	Northwood	United Kingdom
10	Nottingham University Hospitals NHS Trust	Nottingham	United Kingdom
11	North West Anglia NHS Trust	Peterborough	United Kingdom
12	Betsi Cadwaladr University Health Board	Rhyl	United Kingdom
13	Airedale NHS Foundation Trust	Steeton	United Kingdom