None listed
Conditions
Brief summary
This study is designed to test the potential activity/benefit, safety and feasibility of adding a drug commonly used for bone protection (denosumab) to an immunotherapy drug (nivolumab) before surgery in patients with non-small cell lung cancer (NSCLC) for whom surgery has been recommended. Who is it for? You may be eligible for this study if you are aged 18 years or above and have a confirmed non-small cell lung cancer (NSCLC) for which surgery has been recommended to remove the cancer. Study details Participants will be randomly allocated (by chance) into one of two groups: in group 1, participants will receive two doses of nivolumab in the month prior to surgery, and in group 2, participants will receive two doses of denosumab in addition to the two doses of nivolumab in the month prior to surgery. Nivolumab is administered intravenously (i.e. directly into the vein) and denosumab is administered subcutaneously (i.e. as in injection under the skin). All participants will then proceed to surgery as planned. After surgery, no further trial medications are offered, but participants may be offered standard therapies according to the opinion of their treating clinicians. Those patients who receive denosumab will also be asked to take vitamin D and calcium supplementation during the course of their denosumab treatment. It is hoped this study will confirm that two doses of nivolumab prior to lung cancer surgery results in significant rates of tumour shrinkage similar to a previous USA study, and that denosumab added to nivolumab may show evidence of better effectiveness.
Interventions
A randomized, 2-arm trial of neoadjuvant (pre-operative) therapy in patients with resectable stage 1A (>2cm) - 3A non-small cell lung cancer (NSCLC). The two arms are as follows:
Arm 1: nivolumab 3 mg/kg intravenously days 1, 15 (followed by surgery on day 29)
Arm 2: nivolumab 3 mg/kg intravenously days 1, 15 PLUS denosumab 120 mg subcutaneously days 1, 15 (followed by surgery on day 29). Note: participants in Arm 2 will also receive daily oral vitamin D and calcium supplementation (doses at the
A randomized, 2-arm trial of neoadjuvant (pre-operative) therapy in patients with resectable stage 1A (>2cm) - 3A non-small cell lung cancer (NSCLC). The two arms are as follows: Arm 1: nivolumab 3 mg/kg intravenously days 1, 15 (followed by surgery on day 29) Arm 2: nivolumab 3 mg/kg intravenously days 1, 15 PLUS denosumab 120 mg subcutaneously days 1, 15 (followed by surgery on day 29). Note: participants in Arm 2 will also receive daily oral vitamin D and calcium supplementation (doses at the discretion of the treating clinician) for the duration of denosumab therapy.
Sponsors
Royal Brisbane and Women's Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- Histological or cytological diagnosis of NSCLC. - Baseline histological specimen from primary tumor (and locoregional lymph node metastasis if clinically suspected) must be available for all patients. - Primary tumor must be measurable on CT scan (RECIST v.1.1 criteria). - Stage IA (>2cm) - IIIA confirmed by FDG-PET scan (it is strongly recommended that mediastinal nodal status in patients with N2 nodes is pathologically confirmed). Staging is according to 8th edition UICC/AJCC 2017. - Considered to be surgically resectable by thoracic surgeon. - No prior therapy for NSCLC. - Age greater than or equal to 18 years. - ECOG Performance Status 0-1. - Peripheral neuropathy no worse than grade I. - Patients on study with reproductive potential, or female partners with reproductive potential, must use an effective contraceptive method during the trial and for 3 months after the completion of chemotherapy. - Adequate organ function including the following: expected FEV1 following surgery greater than or equal to 1.0 L/sec adequate bone marrow reserve: ANC at least 1.5 x 109/L, platelets at least 100 x 109/L, haemoglobin at least 100 g/L hepatic: bilirubin at least 1.5 times ULN; ALP, AST and/or ALT at least 3 times ULN renal: creatinine clearance at least 60 mL/min (calculated). If the creatinine clearance is between 50 and 60 mL/min, then determination of glomerular filtration rate by nuclear medicine scan may be carried out and this result used for eligibility. - Ability to give written informed consent.
Exclusion criteria
- Small cell or mixed small cell histology subtypes. - Known active neoplastic disease present for 5 years before enrolment, other than non-melanoma skin cancer or adequately treated stage I in situ cervical cancer. - Patients receiving another investigational drug or anti-cancer treatment within 4 weeks prior to 1st infusion of study medication. - Previous treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways. - Previous treatment with denosumab. - Active infection, which in the opinion of the Investigator would compromise the patient’s ability to tolerate therapy. - Currently pregnant or breast feeding. - Serious concomitant medical or psychiatric disorders which would compromise the safety of the patient or their ability to receive study therapy or complete the study. - Significant cardiovascular disease. - Patient in whom corticosteroid premedication is contraindicated. - Active, known or suspected autoimmune disease. - Any condition requiring systemic treatment with either corticosteroids (>10mg daily prednisone or equivalent dose of an alternative corticosteroid) or other immunosuppressive medications within 14 days of study drug administration. - History of severe hypersensitivity reactions to any of the study medications. - Have received a recent (within 30 days) or are receiving concurrent yellow fever vaccination or other live attenuated vaccination. - Unhealed or planned dental/oral surgery, current or previous osteonecrosis or osteomyelitis of the jaw.
Outcome results
None listed