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

A Phase II, Multicentre, Randomised Trial Comparing Combination Gemcitabine/Carboplatin and Hydroxychloroquine Versus Carboplatin/Etoposide Therapy Alone in Small Cell Lung Cancer (SCLC)

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)

Study Overview

• Status: Terminated
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: Gemcitabine; Drug: Carboplatin; Drug: Etoposide; Drug: Hydroxychloroquine

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 Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression free survival	Defined as the time from randomisation to first progression/death (whichever came first), assessed up to 41 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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
Adverse events	Including ophthalmologic and treatment specific toxicities	From date of consent to 30 days after final trial treatment
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
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
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
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
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

Collaborators and Investigators

• Sponsor: University College, London

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 14, 2017
• Primary Completion (ACTUAL): March 12, 2021
• Study Completion (ACTUAL): March 12, 2021

Study Registration Dates

• First Submitted: March 8, 2016
• First Submitted That Met QC Criteria: March 23, 2016
• First Posted (ESTIMATE): March 30, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 18, 2021
• Last Update Submitted That Met QC Criteria: March 16, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Gemcitabine; Carboplatin; Etoposide; Hydroxychloroquine
• Other Study ID Numbers: UCL/12/0515

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No