IVORAD - 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.
- Conditions
- Advanced non-small cell lung cancer, progressing after first of second line chemotherapyCancer - Lung - Non small cell
- Registration Number
- ACTRN12616000352404
- Lead Sponsor
- niversity of Sydney
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Stopped early
- Sex
- All
- Target Recruitment
- 50
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.
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method