Denosumab in Combination With Chemotherapy as First-line Treatment of Metastatic Non-small Cell Lung Cancer

Amgen

Status and phase: Completed; Phase 2

Conditions: Non-Small Cell Lung Cancer

Treatments: Drug: Placebo to Denosumab; Drug: Zoledronic acid; Drug: Standard Chemotherapy; Drug: Denosumab; Drug: Placebo to Zoledronic Acid

Study type: Interventional

Funder types: Industry

Identifiers

NCT01951586

20120249

2013-001662-42 (EudraCT Number)

Details and patient eligibility

About

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

Full description

This is a global randomized double-blind placebo-controlled study in patients with Stage IV untreated non-small cell lung cancer (NSCLC) with or without bone metastasis. Eligible participants are to receive 4 to 6 cycles of a standard of care platinum-doublet chemotherapy regimen. Participants will be randomized in a 2:1 ratio to receive denosumab or matching placebo with the first investigational product dose coinciding with participant's first cycle of chemotherapy and continuing until the primary analysis, unacceptable toxicity, withdrawal of consent, death, or lost to follow-up. Participants who discontinued the investigational product early (ie, before primary analysis) were followed for disease status and survival. The primary analysis took place when 149 events of death had been reported. All participants were followed for 2 years after the last dose of blinded investigational product.

Enrollment: 226 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed stage IV non-small cell lung carcinoma (NSCLC), according to 7th Tumor/Node/Metastasis (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 Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria

• Other inclusion criteria may apply

Exclusion criteria

• Known presence of documented sensitizing epidermal growth factor receptor (EGFR) activating mutation or echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (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 randomization) 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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226 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants received placebo matching to denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.

Treatment:

Drug: Zoledronic acid

Drug: Placebo to Denosumab

Drug: Standard Chemotherapy

Denosumab

Experimental group

Description:

Participants received 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.

Treatment:

Drug: Placebo to Zoledronic Acid

Drug: Denosumab

Drug: Standard Chemotherapy