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No longer recruiting (closed or complete)Last updated: 3 April 2025

NIVORAD: This phase II trial is evaluating an immunotherapy (Nivolumab) and stereotactic ablative body radiotherapy in patients with advanced Non-Small Cell (NSC) Lung Cancer whose cancer has gotten worse following chemotherapy treatmentA randomised phase 2 trial of nivolumab and stereotactic ablative body radiotherapy in advanced non-small cell lung cancer, progressing after first or second line chemotherapy.

Trial purpose

Medical clipboardCancer treatment

Tumor type

Lung Cancers Lung cancer

Age

People18+

Trial acronym

NIVORAD

Clinical summary

Summary

The aim of this study is to determine the activity and safety of treating an asymptomatic, extrathoracic metastasis with a single fraction of SABR, during immunotherapy with nivolumab in advanced NSCLC progressing after 1 or 2 lines of chemotherapy. Who is it for? Adults with advanced non-small-cell lung cancer (NSCLC) progressing after 1 or 2 lines of chemotherapy and with an asymptomatic, extrathoracic metastasis suitable for SABR. Tumour blocks must be available to test for PD-L1 expression. Study details Participants will be randomly allocated in a ratio of 2:1 to either nivolumab 240mg every 2 weeks plus SABR (experimental) or nivolumab 240mg every 2 weeks alone (control). Nivolumab is continued until disease progression or prohibitive toxicity. Participants will be assessed regularly for treatment response and side effects during the treatment and follow up phase. Clinical assessments will be performed before each cycle of nivolumab (2 weekly) and CT scans at baseline, week 6, 12, 18, 24 then 12 weekly until progression. Anticancer treatments and survival will be reviewed every 12 weeks after progression. This will enable us to determine the activity and safety of each treatment option in patients with an asymptomatic, extrathoracic metastasis.

Conditions

This trial is treating people with Non-Small Cell (NSC) Lung Cancer

Eligibility

Inclusion

1. Adult (18 years or over) with a histologically or cytologically confirmed diagnosis of NSCLC.
2. At least one site of disease which is suitable for stereotactic radiotherapy, but for which radiotherapy is NOT URGENTLY REQUIRED at this time. The lesion is not required to be measurable or evaluable and must be nominated before randomisation. This lesion will be irradiated in patients randomised to receive radiation. The following criteria for the irradiated lesion must be met;
• Location must exclude the mediastinum and the central nervous system (vertebrae are allowed)
• Lesion size must be <=50mm and must not have been previously irradiated
3. At least one lesion (target or non-target according to RECIST 1.1) that is separate and in addition to the lesion nominated for irradiation. This lesion cannot have been irradiated previously.
4. Must have progressed after receiving 1 or 2 lines of chemotherapy for advanced disease including a platinum-based doublet. Maintenance chemotherapy following first line chemotherapy is considered a second line of chemotherapy. Relapse within 12 months of completing curative-intent platinum-based chemotherapy given either as adjuvant to surgery or as concurrent or sequential chemo-radiotherapy is considered one line of chemotherapy.
5. ECOG performance status of 0 or 1 at the time of randomisation.
6. Adequate bone marrow function (done within 14 days prior to randomisation and with values within the ranges specified below). Blood transfusions are permissible.
• White blood cell count >= 2 x 109/L
• Absolute neutrophil count >= 1.5 x 109/L
• Platelets >= 100 x 109/L
• Haemoglobin >= 90 g/L
7. Adequate liver function (done within 14 days prior to randomisation and with values within the ranges specified below):
• Alanine transaminase <= 3 x upper limit of normal (ULN)
• Aspartate aminotransferase <= 3 x ULN
• Total bilirubin <= 1.5 x ULN (except patients with Gilbert Syndrome, who can have total bilirubin <= 5 x ULN)
8. Adequate renal function (done within 14 days prior to randomisation and with values within the ranges specified below):
• Serum creatinine <=1.5 x ULN
or
• Creatinine clearance (CrCl) >=40 mL/min (use Cockcroft-Gault formula as per appendix 6)
9. Tumour tissue (formalin-fixed paraffin embedded) should be available for PD-L1 testing and can be provided as a block or slides (archival tissue is acceptable). For patients without histological tumour tissue available, every attempt should be made to provide a cell block or unstained cytology slides. Patients will not be selected by PD-L1 status.
10. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
11. Signed, written informed consent.

Exclusion

1. Active, known or suspected autoimmune disease. Patients are not excluded if they have vitiligo, type 1 diabetes mellitus, residual hypothyroidism due to an autoimmune condition requiring only hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
2. Any condition requiring systemic treatment with either regular corticosteroids (>10mg daily prednisone or equivalent dose of an alternative corticosteroid) or other immunosuppressive medications within 14 days of study drug administration. Intranasal, inhaled or topical steroids are permitted in the absence of active autoimmune disease.
3. Patients with leptomeningeal or uncontrolled brain metastases are excluded. Controlled brain metastases are those which have been treated and are radiologically and/or clinically stable, and the patient is asymptomatic and does not require corticosteroids.
4. Actionable mutation for which an approved, targeted therapeutic is available, e.g. known mutation of epidermal growth factor receptor (EGFR) or translocation of anaplastic lymphoma kinase.
5. Chemotherapy in the last 4 weeks.
6. Radiotherapy in the last 2 weeks.
7. Prior therapy with an 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.
8. Current treatment with other investigational drugs or anti-cancer therapy.
9. Life expectancy of less than 3 months.
10. History of another malignancy within 3 years prior to randomisation. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 3 years after definitive primary treatment.
11. Receipt of live attenuated vaccination within 30 days prior to registration.
12. Positive test for hepatitis B virus surface antigen (HBVsAg) or antibodies to hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
13. History of other significant infection, including HIV. HIV testing not mandatory unless clinically indicated.
14. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
15. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception to avoid pregnancy for 23 weeks after the last dose of nivolumab. Women of childbearing potential must have a negative pregnancy test done within 24 hours prior to randomisation. Men must have been surgically sterilised or use a (double if required) barrier method of contraception if they are sexually active with a woman of child bearing potential for a period of 31 weeks after the last dose of nivolumab.
16. Recipients of a transplanted solid organ (kidney, liver, heart, lung) or of allogeneic bone marrow.


Inclusion

  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
  • You are currently being treated on a clinical trial.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

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Trial Identifiers

Information on this page is partially produced from ANZCTR *. View further details about this trial on the registry via the links below:

Trial sponsor

University of Sydney

Scientific Title

A randomised phase 2 trial of nivolumab and stereotactic ablative body radiotherapy in advanced non-small cell lung cancer, progressing after first or second line chemotherapy.

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