Study of Gemcitabine/Carboplatin First-line Chemotherapy +/- Apatorsen in Advanced Squamous Cell Lung Cancers

NCT02423590 | Unknown Phase 2 DMC

• 1 other identifier: 009436QM
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 20

Brief Summary

This study is being carried out to see if a new drug called Apatorsen in combination with standard gemcitabine/carboplatin chemotherapy is effective in treating squamous cell lung cancer. This study is part of a research project for collecting information about the effectiveness and safety of Apatorsen when used with gemcitabine/carboplatin chemotherapy. The main purpose of this study is to see if Apatorsen, when combined with gemcitabine/carboplatin, is an effective treatment for squamous cell lung cancer. Recent research has found that a protein called Hsp27 can help cancer cells protect themselves against the effects of cancer treatments. Hsp27 is only found in some lung cancers but when it is present, cancer drugs might not work as well as they would without Hsp27 being present. Blocking the action of Hsp27 or removing Hsp27 from cancer cells with Apatorsen may slow down or stop the cancer growing. This study will therefore look at the relationship between the Hsp27 levels in tumour and blood and the effect of the treatment. The development of Apatorsen is intended to provide a new treatment option for patients with cancer. Apatorsen may also make the cancer more sensitive to gemcitabine and carboplatin and so make this chemotherapy treatment more effective.

Conditions

Squamous Cell Lung Cancer

Keywords

Squamous; Lung; Apatorsen

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival as measured by investigator-assessed (using RECIST 1.1) progression-free survival

  Progression-free survival, defined as the time from the date of randomisation to the date of first documented tumour progression based on investigator assessment (using RECIST 1.1) or death from any cause, whichever occurs first.

  Date of patient randomisation to the date of first documented tumour progression (estimated 7.5 months) or death

Secondary Outcomes (6)

• Clinical Activity as measured by response rate (RECIST 1.1), change in tumour size, disease control rate, and duration of response of gemcitabine/carboplatin + Apatorsen relative to gemcitabine/carboplatin alone

  At 12 weeks and 24 weeks post-randomisation until disease progression (estimated 7.5 months)

• Overall survival benefit of gemcitabine/carboplatin + Apatorsen relative to gemcitabine/carboplatin alone

  Date of randomisation to date of death (expected average 12 months)

• Clinical benefit as measured by investigator assessment using RECIST 1.1

  At 12 and 24 weeks post-randomisation

• Drug exposure measured as average dose per week

  4-6 cycles of treatment (12-18 weeks) and for apatorsen arm until disease progression (estimated 7.5 months)

• Compare the differences in health-related Quality of Life (HRQL) and symptoms for patients by treatment assignment as measured by the Functional Assessment of Cancer Therapy-Lung (FACT-L) scale, and the Euro-QOL 5D (EQ-5D)

  Baseline, once every 3 weeks for 18 weeks and 4 weeks after last dose (estimated 8.8 months)

Other Outcomes (2)

• Alterations in DNA and RNA

  Baseline, day 1 of each cycle (each cycle is 21 days), every 3 weeks during maintenance and 4 weeks after last dose (estimated 8.5 months)

• Clinical Benefit, defined as number of patients with complete or partial response or stable disease maintained ≥24 weeks (as assessed by the site radiologist and/ or investigator, using RECIST 1.1)

  24 weeks until progression (estimated 7.5 months)

Study Arms (2)

Gemcitabine/Carboplatin

ACTIVE COMPARATOR

Gemcitabine/carboplatin will be administered as standard 21-day treatment cycles according to normal clinical practice. * Gemcitabine will be given by 30 minute intravenous infusions on Day 1 and Day 8 of each 21-day Cycle. * On Day 1, carboplatin (AUC5) will be given by infusion over 30-60 minutes.

Drug: Gemcitabine; Drug: Carboplatin

Gemcitabine/carboplatin + Apatorsen

EXPERIMENTAL

* Apatorsen (OGX-427) will be administered as an intravenous infusion over 2 hours. * Apatorsen (OGX-427) treatment will begin with a loading dose period prior to the initiation of chemotherapy. Patients will receive three loading doses of 400 mg within a 9-day period with at least 48 hours between infusions and between the last loading dose infusion and Day 1 of initiating chemotherapy. Chemotherapy must be initiated within 7 calendar days once the last loading dose infusion has been completed. * Following the loading dose period, Apatorsen (OGX-427) will be given weekly at a dose of 400 mg by 2 hour intravenous infusions. On days when both chemotherapy and Apatorsen (OGX-427) are given, Apatorsen (OGX-427) should be given first followed by chemotherapy.

Drug: Apatorsen (OGX-427); Drug: Gemcitabine; Drug: Carboplatin

Interventions

Apatorsen (OGX-427) DRUG

Apatorsen (OGX-427) is a second generation antisense oligonucleotide designed to bind to Hsp27 mRNA

Also known as: Apatorsen, OGX-427

Gemcitabine/carboplatin + Apatorsen

Gemcitabine DRUG

Gemcitabine is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Gemcitabine is classified as an antimetabolite

Also known as: US Brand Name: Gemzar

Gemcitabine/Carboplatin; Gemcitabine/carboplatin + Apatorsen

Carboplatin DRUG

Carboplatin is an anticancer drug ("antineoplastic" or "cytotoxic") chemotherapy drug. Carboplatin is classified as an "alkylating agent."

Also known as: Trade name: Paraplatin ®

Gemcitabine/Carboplatin; Gemcitabine/carboplatin + Apatorsen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent prior to admission to this study
• Histological or cytological diagnosis of squamous non-small cell lung cancer. Patients with adenosquamous or mixed histology are not eligible for this study.
• Stage IIIB disease that is unsuitable to radio-chemotherapy or Stage IV disease or recurrent NSCLC; recurrent disease must not be amenable to resection or radical radiotherapy with curative intent.
• Patients must have:
• at least one lesion, not previously irradiated, that can be measured accurately at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) OR
• lytic or mixed (lytic + sclerotic) bone lesions in the absence of measurable disease as defined above
• Willing to donate archival diagnostic tissue for translational research, if available.
• Haematologic and biochemical indices within the ranges shown below. These measurements must be performed within one week prior to randomisation
• ANC ≥1.5 x 109/L;, platelet count ≥100 x 109/L,
• Serum creatinine \< 1.5 times the upper limit of normal (ULN)
• Bilirubin level \< 1.5 X ULN
• AST or ALT \<3.0 X ULN or \<5 X ULN in the presence of liver metastases
• ECOG performance status 0-2
• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant)
• Male or Female aged ≥18 years

You may not qualify if:

• Symptomatic CNS involvement or CNS involvement requiring steroid therapy; patients with treated brain metastases that are asymptomatic and have been clinically stable for 1 month will be eligible for protocol participation
• Previous systemic treatment for lung cancer (exception for patients who have previously received immunotherapy without chemotherapy, and for patients with recurrent disease: adjuvant chemotherapy is allowed as long as this was finished at least 1 year prior to enrolment and did not contain gemcitabine)
• Known tumour EGFR mutation, unless contraindication to EGFR-directed therapy
• Known tumour ALK rearrangements, unless contraindication to Alk-directed therapy or Alk-directed therapy not available 1
• Pre-existing sensory or motor polyneuropathy \>Grade 2 according to NCI CTCAE
• Significant cardiovascular disease, such as
• History of myocardial infarction, acute coronary syndromes (including unstable angina), or history of coronary angioplasty/stenting/bypass grafting within past 6 months.
• History of symptomatic congestive heart failure (CHF) New York Heart Association (NYHA) Classes III-IV.
• Severe cardiac arrhythmia requiring medication or severe conduction abnormalities
• Poorly controlled hypertension (resting diastolic blood pressure \>115 mmHg)
• Clinically significant valvular disease, cardiomegaly, ventricular hypertrophy, or cardiomyopathy
• Active second malignancy (except non-melanomatous skin cancer): active secondary malignancy is defined as a current need for cancer therapy or a high possibility (\>30%) of recurrence during the study.
• Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study entry.
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent.
• Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol.

Sponsors & Collaborators

• Queen Mary University of London: lead
• Achieve Life Sciences: collaborator

Study Sites (20)

Royal Cornwall Hospitals NHS Trust

Truro, Cornwall, TR1 3LQ, United Kingdom

Location

Medway NHS Foundation Trust

Gillingham, Kent, ME7 5NY, United Kingdom

Location

Heart of England NHS Foundation Trust

Birmingham, B9 5SS, United Kingdom

Location

University Hospitals Bristol NHS Foundation Trust

Bristol, BS2 8ED, United Kingdom

Location

Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

Location

Colchester Hospital University NHs Foundation Trust

Colchester, CO3 3NB, United Kingdom

Location

Betsi Cadwaladr University Health Board

Denbighshire, LL18 5UJ, United Kingdom

Location

NHS Tayside

Dundee, DD2 1UB, United Kingdom

Location

Royal Surrey County Hospital NHS Foundation Trust

Guildford, GU2 7XX, United Kingdom

Location

NHS Highland

Inverness, IV2 3UJ, United Kingdom

Location

Barts Health NHS Trust

London, EC1M 6BQ, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, NW1 2PG, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

Lewisham and Greenwich NHS Trust

London, SE13 6LH, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG5 1PB, United Kingdom

Location

Royal Berkshire NHS Foundation Trust

Reading, RG1 5AN, United Kingdom

Location

Abertawe Bro Morgannwg University Health Board

Swansea, SA2 8QA, United Kingdom

Location

Weston Area Health NHS Trust

Weston-super-Mare, BS23 4TQ, United Kingdom

Location

Yeovil District Hospital NHS Foundation Trust

Yeovil, BA21 4AT, United Kingdom

Location

MeSH Terms

Interventions

apatorsen; Gemcitabine; Carboplatin

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Study Officials

• Peter Schmid, Prof.

  Queen Mary University London

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2014
• First Posted: April 22, 2015
• Study Start: June 1, 2014
• Primary Completion: May 1, 2018
• Study Completion: June 1, 2018
• Last Updated: August 22, 2017

Record last verified: 2017-08

Locations

GB (20)