Back to resultsSTUDY 15 - Comparing Gemcitabine/Carboplatin and Hydroxychloroquine Versus Carboplatin/Etoposide Therapy Alone in Small Cell Lung Cancer (SCLC)
Primary Purpose
Small Cell Lung Cancer
Status
Terminated
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Gemcitabine
Carboplatin
Etoposide
Hydroxychloroquine
Sponsored by
About this trial
This is an interventional treatment trial for Small Cell Lung Cancer
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
Sites / Locations
- Dorset County Hospital NHS Foundation Trust
- Royal Surrey County Hospital
- The Princess Alexandra Hospital NHS Trust
- University Hospitals of Morecambe Bay NHS Foundation Trust
- University Hospital Leicester NHS Trust
- Guy's and St Thomas' Hospitals NHS Foundation Trust
- UCLH
- The Christie
- East and North Herts NHS Foundation Trust
- Nottingham University Hospitals NHS Trust
- North West Anglia NHS Trust
- Betsi Cadwaladr University Health Board
- Airedale NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Control Arm
Investigational Arm
Arm 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
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)
Outcomes
Primary Outcome Measures
Progression free survival
Secondary Outcome Measures
Overall survival
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)
Adverse events
Including ophthalmologic and treatment specific toxicities
Quality of life as measured by EQ-5D
The questionnaire is a standardised questionnaire
Quality of life as measured by QLQC-30
The questionnaire is a standardised questionnaire
Quality of life as measured by QLQ-LC-13
The questionnaire is a standardised questionnaire
Compliance measured by dose intensity
Capturing dose delays, modifications and omissions
Compliance measured by dose exposure
Capturing dose delays, modifications and omissions
Full Information
NCT ID
NCT02722369
First Posted
March 8, 2016
Last Updated
March 16, 2021
Sponsor
University College, London
1. Study Identification
Unique Protocol Identification Number
NCT02722369
Brief Title
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
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Terminated
Why Stopped
Low recruitment, lack of efficacy and increased adverse events in investigational arm.
Study Start Date
March 14, 2017 (Actual)
Primary Completion Date
March 12, 2021 (Actual)
Study Completion Date
March 12, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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)
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
72 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Control Arm
Arm Type
Active Comparator
Arm 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
Arm Title
Investigational Arm
Arm Type
Experimental
Arm 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)
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Chemotherapy
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Chemotherapy
Intervention Type
Drug
Intervention Name(s)
Etoposide
Intervention Description
Chemotherapy
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Intervention Description
Maintenance Agent
Primary Outcome Measure Information:
Title
Progression free survival
Time Frame
Defined as the time from randomisation to first progression/death (whichever came first), assessed up to 41 months
Secondary Outcome Measure Information:
Title
Overall survival
Time Frame
From date of randomisation to death due to any cause, assessed up to 41 months
Title
Objective response as measured by Response Evaluation Criteria in Solid Tumours (RECIST) v.1.1
Description
Complete Response (CR)/ Partial Response (PR)/ Progressive Disease (PD)/ Stable Disease (SD)
Time Frame
From first tumour assessment to progression/trial end (whichever is first), assessed up to 41 months
Title
Adverse events
Description
Including ophthalmologic and treatment specific toxicities
Time Frame
From date of consent to 30 days after final trial treatment
Title
Quality of life as measured by EQ-5D
Description
The questionnaire is a standardised questionnaire
Time Frame
From baseline to progression/trial end (whichever is first), assessed up to 41 months
Title
Quality of life as measured by QLQC-30
Description
The questionnaire is a standardised questionnaire
Time Frame
From baseline to progression/trial end (whichever is first), assessed up to 41 months
Title
Quality of life as measured by QLQ-LC-13
Description
The questionnaire is a standardised questionnaire
Time Frame
From baseline to progression/trial end (whicenver is first), assessed up to 41 months
Title
Compliance measured by dose intensity
Description
Capturing dose delays, modifications and omissions
Time Frame
From first date of trial treatment to progression/trial end (whichever is first), assessed up to 41 months
Title
Compliance measured by dose exposure
Description
Capturing dose delays, modifications and omissions
Time Frame
From first date of trial treatment to progression/trial end (whichever is first), assessed up to 41 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Dorset County Hospital NHS Foundation Trust
City
Dorchester
Country
United Kingdom
Facility Name
Royal Surrey County Hospital
City
Guildford
Country
United Kingdom
Facility Name
The Princess Alexandra Hospital NHS Trust
City
Harlow
Country
United Kingdom
Facility Name
University Hospitals of Morecambe Bay NHS Foundation Trust
City
Lancaster
Country
United Kingdom
Facility Name
University Hospital Leicester NHS Trust
City
Leicester
Country
United Kingdom
Facility Name
Guy's and St Thomas' Hospitals NHS Foundation Trust
City
London
Country
United Kingdom
Facility Name
UCLH
City
London
Country
United Kingdom
Facility Name
The Christie
City
Manchester
Country
United Kingdom
Facility Name
East and North Herts NHS Foundation Trust
City
Northwood
Country
United Kingdom
Facility Name
Nottingham University Hospitals NHS Trust
City
Nottingham
Country
United Kingdom
Facility Name
North West Anglia NHS Trust
City
Peterborough
Country
United Kingdom
Facility Name
Betsi Cadwaladr University Health Board
City
Rhyl
Country
United Kingdom
Facility Name
Airedale NHS Foundation Trust
City
Steeton
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
On receipt of a request the recipient will consider the proposal, ensure relevant Chief Investigator/Trial Management Group are consulted and, if necessary, Trial Steering Committee and/or Cancer Trials Centre (CTC) Senior Management Group. Any shared data will be in an anonymised format
Learn more about this trial
STUDY 15 - Comparing Gemcitabine/Carboplatin and Hydroxychloroquine Versus Carboplatin/Etoposide Therapy Alone in Small Cell Lung Cancer (SCLC)
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