This trial is active, not recruiting.

Condition non-small cell lung cancer
Treatments denosumab, zometa
Phase phase 2
Target RANKL
Sponsor Amgen
Start date December 2013
End date July 2016
Trial size 226 participants
Trial identifier NCT01951586, 20120249


This randomized phase 2 trial is studying the effect of adding denosumab to standard chemotherapy in the treatment of advanced lung cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
(Placebo Comparator)
Placebo will be administered.
zometa zoledronic acid
For the prevention of skeletal complications in subjects with bone metastasis who are not randomized to receive denosumab, zoledronic acid will be offered in a blinded manner through assignment by the IWRS/IVRS upon the request of the investigator.
Denosumab will be administered
denosumab XGEVA
Denosumab will be administered

Primary Outcomes

Relative benefit on overall survival (OS)
time frame: 36 months

Secondary Outcomes

Tumor Tissue RANK expression in correlation with overall survival
time frame: 36 months
Tumor tissue RANK expression in correlation with objective response rate (CR+PR) based on modified RECIST 1.1
time frame: 36 months
Tumor tissue RANKL expression in correlation with overall survival
time frame: 36 months
Tumor tissue RANKL expression in correlation with objective response (CR + PR) based on modified RECIST 1.1
time frame: 36 months
Objective response, clinical benefit rate & progression-free survival based on modified RECIST 1.1
time frame: 36 months
Serum denosumab trough levels
time frame: 36 months
Treatment-emergent adverse events
time frame: 36 months

Eligibility Criteria

Male or female participants from 18 years up to 100 years old.

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 - Other inclusion criteria may apply 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) - Any prior systemic therapy (before randomisation) 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 - Significant dental/oral disease, including prior history or current evidence of osteonecrosis/ osteomyelitis of the jaw, or with the following: - Active dental or jaw condition which requires oral surgery - Non-healed dental/oral surgery - Planned invasive dental procedures for the course of the study.

Additional Information

Official title A Randomized, Double-blind, Multi-center Phase 2 Trial of Denosumab in Combination With Chemotherapy as First-line Treatment of Metastatic Non-small Cell Lung Cancer
Description This is a global phase 2 randomized double-blind placebo-controlled study in subjects with Stage IV untreated NSCLC with or without bone metastasis. Eligible subjects are to receive 4 to 6 cycles of a standard of care platinum-doublet chemotherapy regimen. Approximately 216 subjects will be randomized in a 2:1 ratio to receive denosumab or matching placebo with the first investigational product dose coinciding with subject's first cycle of chemotherapy and continuing until the primary analysis, unacceptable toxicity, withdrawal of consent, death, or lost to follow-up. Subjects will be offered open label denosumab if study results show a positive benefit:risk profile, or be followed long-term, for up to 2 years. All subjects are to receive daily dietary supplements of at least 500 mg of calcium and 400 IU of vitamin D.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Amgen.
Location data was received from the National Cancer Institute and was last updated in August 2016.