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

Small Cell Lung Cancer Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02722369
• Other study ID #: UCL/12/0515
• Status: Terminated
• Phase: Phase 2
• Start date: March 14, 2017
• Est. completion date: March 12, 2021

Study information

• Verified date: March 2021
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 72
• Est. completion date: March 12, 2021
• Est. primary completion date: March 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• Gemcitabine
Chemotherapy
• Carboplatin
Chemotherapy
• Etoposide
Chemotherapy
• Hydroxychloroquine
Maintenance Agent

Locations

Country	Name	City	State
United Kingdom	Dorset County Hospital NHS Foundation Trust	Dorchester
United Kingdom	Royal Surrey County Hospital	Guildford
United Kingdom	The Princess Alexandra Hospital NHS Trust	Harlow
United Kingdom	University Hospitals of Morecambe Bay NHS Foundation Trust	Lancaster
United Kingdom	University Hospital Leicester NHS Trust	Leicester
United Kingdom	Guy's and St Thomas' Hospitals NHS Foundation Trust	London
United Kingdom	UCLH	London
United Kingdom	The Christie	Manchester
United Kingdom	East and North Herts NHS Foundation Trust	Northwood
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	North West Anglia NHS Trust	Peterborough
United Kingdom	Betsi Cadwaladr University Health Board	Rhyl
United Kingdom	Airedale NHS Foundation Trust	Steeton

Sponsors (1)

Lead Sponsor	Collaborator
University College, London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival		Defined as the time from randomisation to first progression/death (whichever came first), assessed up to 41 months
Secondary	Overall survival		From date of randomisation to death due to any cause, assessed up to 41 months
Secondary	Objective response as measured by Response Evaluation Criteria in Solid Tumours (RECIST) v.1.1	Complete Response (CR)/ Partial Response (PR)/ Progressive Disease (PD)/ Stable Disease (SD)	From first tumour assessment to progression/trial end (whichever is first), assessed up to 41 months
Secondary	Adverse events	Including ophthalmologic and treatment specific toxicities	From date of consent to 30 days after final trial treatment
Secondary	Quality of life as measured by EQ-5D	The questionnaire is a standardised questionnaire	From baseline to progression/trial end (whichever is first), assessed up to 41 months
Secondary	Quality of life as measured by QLQC-30	The questionnaire is a standardised questionnaire	From baseline to progression/trial end (whichever is first), assessed up to 41 months
Secondary	Quality of life as measured by QLQ-LC-13	The questionnaire is a standardised questionnaire	From baseline to progression/trial end (whicenver is first), assessed up to 41 months
Secondary	Compliance measured by dose intensity	Capturing dose delays, modifications and omissions	From first date of trial treatment to progression/trial end (whichever is first), assessed up to 41 months
Secondary	Compliance measured by dose exposure	Capturing dose delays, modifications and omissions	From first date of trial treatment to progression/trial end (whichever is first), assessed up to 41 months