This study will be carried out to gain more knowledge about denosumab in patientes with NSCLC. The effect of denosumab in combination with platinum-doublet chemotherapy in patients with NSCLC and the relation with the presence of biomarkers in…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To estimate the treatment effect of the combination of denosumab and standard
of care (SOC) versus SOC alone on overall survival (OS).
Secondary outcome
To assess whether any relative benefit on OS from the combination of denosumab
and SOC versus SOC alone in NSCLC is associated with tumor RANK expression
Background summary
Post-hoc analysis of a lung canccer subset in other studies suggested an
advantage in overall survival in teh comaprison of denosumab vs. zoledronic
acid. In addition, there is an unmet medical need for molecularly targeted
therapies in metastatic NSCLC.
Study objective
This study will be carried out to gain more knowledge about denosumab in
patientes with NSCLC. The effect of denosumab in combination with
platinum-doublet chemotherapy in patients with NSCLC and the relation with the
presence of biomarkers in tumorcells will be studied.
Study design
The study consists of 2 patrts:
1) Screening
Patients will undergo study assessmnets to check if in and exclusion criteria
are fullfilled. Eligble patients will start the treatment phase
2) Treatment phase
Patients will be randomised (2:1) in one of the following arms:
- Arm 1: denosumab 120 mg subcutaneous 4-weekly or 3-weekly + loading dosis on
day 8 + 4-6 cycli standard chemotherapy
- Arm 2: placebo subcutaneous 4-weekly or 3-weekly + loading dosis on day 8 +
4-6 cycli standard chemotherapy
144 patients will be randomised in arm 1 and 72 in arm 2. In total 216 subjects
will participate in teh study.
After 4-6 cycli, subjects randomized in arm 1 will receive denosumab 120 mg
subcuteneous 4-weekly or 3-weekly and standard chemotherapy (as maintenance
therapy of extra cycli). Patients randomised in arm 2 receive placebo
subcuteneous 4-weekly or 3-weekly and standard chemotherapy (as maintenance
therapy of extra cycli). All patients receive calcium and vitamin D supplements
during the treatment phase
The treatment phase ends whne the primary endpoint has been raeched, the
patient has died or is lost to follow up.
Added in protocol amendment 2: If denosumab is determined to have a positive
benefit:risk profile in this study, all subjects currently undergoing scheduled
assessments will be offered open-label denosumab at a dose of 120 mg SC for up
to 2 years. If the benefit:risk profile is not positive, all subjects will be
followed for up to 2 years after the last dose of blinded investigational
product.
Intervention
Eligible patients will be treated with denosumab 120 mg subcutaneous 4-weekly
or 3-weekly + 4-6 cycli van standard chemotherapy or placebo subcutaneous
4-weekly or 3-weekly + 4-6 cycli van standard chemotherapy
Study burden and risks
Risk: adverse events of denosumab. During the visits to the hospital the
subjects will be monitored for adverse events.
Burden: maximum study duration is about 5 years. The subject will visite the
hosppital every 3-4 weeks. The duration of each visit will vary from 3-4 hours
Minervum 7061
Breda 4800 DH
NL
Minervum 7061
Breda 4800 DH
NL
Listed location countries
Age
Inclusion criteria
- Histologically or cytologically confirmed stage IV non-small cell lung carcinoma
(NSCLC), according to 7th TNM classification (cytological specimens obtained by
bronchial washing or brushing, or fine-needle aspiration are acceptable)
- Subject has available and has provided consent to release to the sponsor (or
designee) a tumor block with confirmed tumor content (or approximately 20
unstained charged slides [a minimum of 7 slides is mandatory]) and the
corresponding pathology report
- Planned to receive 4 to 6 cycles of pemetrexed or gemcitabine in combination
with cisplatin or carboplatin
* For subjects to receive pemetrexed, planned to receive vitamin B12 and
folate per pemetrexed approved labeling
- Radiographically evaluable (measurable or non-measurable) disease (according
to modified RECIST 1.1 criteria, Appendix E)
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Male or female subjects * 18 years of age at the time of screening
- Adequate organ function, as defined by the following criteria:
*Serum aspartate aminotransferase (AST) * 2.5 x upper limit of normal (ULN)
(or AST * 5 x upper limit of normal (ULN) if liver metastases are present)
*Serum alanine aminotransferase (ALT) * 2.5 x ULN (or ALT * 5 x upper limit
of normal (ULN) if liver metastases are present)
*Serum total bilirubin (TBL) * 1.5 x ULN (or * 2.0 x upper limit of normal (ULN)
if liver metastases are present)
*Creatinine clearance * 45 mL/min (refer to section 6.3.1.3 for Cockcroft*Gault
formula)
- Serum calcium or albumin-adjusted serum calcium * 2.0 mmol/L
- Expected life expectancy of at least 3 months
- Subject has provided or subject*s legally acceptable representative has provided
informed consent prior to any study-specific activities/procedures being initiated
Exclusion criteria
- Known presence of documented sensitizing epidermal growth factor receptor
(EGFR) activating mutation or EML4-ALK translocation (screening following local
standards, but strongly encouraged in non-squamous histology)
- Known brain metastases (systematic screening of patients not mandatory)
- Prior systemic therapy for the treatment of NSCLC (including chemoradiation),
except if for non-metastatic disease and was completed at least 6 months prior to
randomization
- Planned to receive bevacizumab
- Central (chest) radiation therapy within 28 days prior to randomization, radiation
therapy to any other site(s) within 14 days prior to randomization
- Prior administration of denosumab
- Subjects with sarcomatoid, carcinoid, and mesenchymal histologies
- More than 1 year of cumulative oral bisphosphonate usage prior to randomization
- More than 1 previous dose of IV bisphosphonate administration prior to
randomization
Please refer to pga 24 of the protocol
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 119157 |
| EudraCT | EUCTR2013-001662-42-NL |
| CCMO | NL45573.008.13 |