Survival imProvement in Lung cancEr iNduced by DenOsUmab theRapy

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02129699
• Date of registration: 30/04/2014
• Prospective Registration: Yes
• Primary sponsor: European Thoracic Oncology Platform
• Public title: Survival imProvement in Lung cancEr iNduced by DenOsUmab theRapy SPLENDOUR
• Scientific title: A Randomised, Open-label Phase III Trial Evaluating the Addition of Denosumab to Standard First-line Anticancer Treatment in Advanced NSCLC
• Date of first enrolment: January 6, 2015
• Target sample size: 514
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02129699
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Austria, Belgium, Bulgaria, France, Germany, Ireland, Israel, Italy, Poland, Romania, Slovenia, Spain, Switzerland, United Kingdom

Contacts

• Name: Sarah Danson, PhD
• Affiliation: EORTC Trial Co-Chair, University of Sheffield, Sheffield, UK

• Name: Rolf Stahel, MD
• Affiliation: Trial Co-Chair, University Hospital of Zuerich, Switzerland

• Name: Mary O'Brien, MD
• Affiliation: EORTC Trial Co-Chair, Royal Marden Hospital, Sutton, UK

• Name: Solange Peters, MD, PhD
• Affiliation: Trial Chair, CHUV Lausanne, Switzerland

Key inclusion & exclusion criteria

Inclusion Criteria:

- Histologically or cytologically confirmed advanced stage IV non-small cell lung
carcinoma (NSCLC), according to 7th TNM classification

- Age = 18 years

- ECOG performance status 0-2

- Measurable or evaluable disease (according to RECIST 1.1 criteria) assessed within 28
days from randomization.

- Availability of tumour tissue (as assessed by the local pathologist) for translational
research:

- preferred: FFPE block from primary tumour or metastasis,

- alternatively: cell block

- if no block available: 10 freshly cut unstained slides.

- Adequate haematological function: neutrophils = 1.5 ×109/L, platelets

= 100×109/L, and hemoglobin = 9 g/dL

- Adequate liver function:

- ALT = 3 × ULN ( = 5 × ULN if liver metastasis are present)

- Total bilirubin < 2 x ULN

- Adequate renal function: calculated renal creatinine clearance (CrCl) = 30 mL/min
(according to the formula of Cockroft-Gault)

- Life expectancy of at least 3 months

- Women of childbearing potential, including women who had their last menstrual period
in the last 2 years, must have a negative serum or urine pregnancy test within 7 days
before enrollment. Pregnancy test has to be repeated within 14 days before treatment
start.

- All sexually active men and women of childbearing potential must use an effective
contraceptive method during the study treatment and for a period of at least 6 months
following the last administration of trial treatment

- Written Informed Consent must be signed and dated by the patient and the investigator
prior to any trial-related intervention for

1. Trial treatment

2. Submission of biomaterial for central testing

Exclusion Criteria:

- Patients with presence of documented sensitizing EGFR activating mutation or ALK
rearrangements (screening following local standards is optional, but strongly
encouraged in non-squamous histology)

- Patients with documented brain metastases (systematic screening of patients not
mandatory; however, if the patient is symptomatic, brain metastases screening is
recommended).

- Prior chemotherapy or molecular targeted therapy for metastatic disease.

Exceptions:

- Neoadjuvant or adjuvant chemotherapy or radio-chemotherapy are allowed if terminated
more than 6 months before registration.

- Previous radical radiotherapy without systemic treatment is allowed.

- One previous line of systemic immunotherapy by checkpoint inhibitors is allowed and
needs to be documented

- Concomitant treatment with immune checkpoint inhibitors

- Any investigational agent(s) within 30 days prior to randomisation

- Concurrent bisphosphonate administration

- Oral/ dental conditions (by visual inspection):

- Prior history or current evidence of osteomyelitis / osteonecrosis of the jaw

- Active dental or jaw condition which requires oral surgery

- Planned invasive dental procedure for the course of the trial

- Non-healed dental or oral surgery

- Evidence of any medical condition which would impair the ability of the patient to
participate in the trial or might preclude therapy with trial drugs (e.g. unstable or
uncompensated respiratory, cardiac, hepatic or renal disease, active infection,
uncontrolled diabetes mellitus; uncontrolled arterial hypertension = 160/100 mmHg,
history of myocardial infarction in the last 3 months)

- Documented active infection with Hepatitis B virus or Hepatitis C virus, known
infection with human immunodeficiency virus (HIV)

- Known hypersensitivity to any of the components of the treatment

- Severe, uncorrected hypocalcaemia or hypercalcaemia:

- hypercalcaemia: total calcium >3.1 mmol/l or corrected calcium (with albumin level) >3
mmol/l

- hypocalcaemia: total calcium <2 mmol/l or corrected calcium (with albumin level) < 1.9
mmol/l

- Legal incapacity or limited legal capacity

- Medical or psychological condition, including uncontrolled arterial hypertension
(>160/110) despite adequate medication which in the opinion of the investigator would
not permit the patient to complete the trial or sign meaningful informed consent

- Women who are pregnant or breastfeeding

- Any concurrent malignancy other than adequately treated basal or squamous cell
carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ breast
carcinoma, or prostate cancer Gleason score < 6. (Patients with a previous malignancy
but without evidence of disease for = 2 years will be allowed to enter the trial)

- Any previous exposure to denosumab, with the exception of a maximum of 2 previous
doses of denosumab (Prolia®) more than 6 month before enrolment for osteoporosis
treatment/prevention.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Lung Cancer Non-small Cell Stage IV

Intervention(s)

Other: None, standard chemotherapy only

Drug: Denosumab

Primary Outcome(s)

Overall survival [Time Frame: Time from the date of randomisation until death from any cause, assessed up to 56 months]

Secondary Outcome(s)

Progression-free survival (PFS) based on RECIST 1.1 [Time Frame: Time from date of randomisation until objective disease progression or death, whichever occurs first, assessed up to 56 months]

Toxicity profile of denosumab [Time Frame: Assessed up to 56 months]

Evaluation of potential predictive biomarkers for denosumab activity [Time Frame: Assessed at baseline, week 7 and at progression (maximum of 56 months)]

Response based on RECIST 1.1 [Time Frame: Response of the tumour is defined according to RECIST 1.1 criteria, assessed up to 56 months]

Secondary ID(s)

SNCTP000000954

20080166

2013-003156-21

ETOP 5-12 / EORTC 08111

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Amgen

European Organisation for Research and Treatment of Cancer - EORTC