RADAR is a multicentre, international, randomised, open-label phase III clinical trial composed of 2 trials running in parallel. Trial 1 will be led and sponsored by University College London (UCL) and conducted in Europe and Australia/New Zealand. Trial 2 will be led by the Canadian Cancer Trials Group (CCTG) and conducted in North America, with CCTG the regulatory sponsor in Canada, and University of Miami the regulatory sponsor and IND holder in the US. Datasets from Trial 1 and Trial 2 will be combined to achieve the total sample size. Data analysis will be performed by UCL and therefore UCL is responsible for the clinicaltrials.gov entry. Eligible patients will be randomised to receive either ABVD or A2VD chemotherapy. An interim PET-CT scan will be performed after 2 cycles of treatment, which will be used to adapt subsequent treatment. Patients will receive a total of 3-4 cycles of chemotherapy and may also receive involved site radiotherapy as consolidation. Patients will be followed up for a minimum of 5 years after treatment.
Eligible patients will be randomised to receive either ABVD chemotherapy (doxorubicin, bleomycin, vinblastine and dacarbazine) or A2VD chemotherapy (doxorubicin, brentuximab vedotin, vinblastine and dacarbazine, with growth factor support). If patients agree, they will have a PET-CT scan after 1 cycle (PET1). The result of this scan will be blinded and used for exploratory endpoints only. Treatment will not be influenced by the result of this scan. All patients will have a PET-CT scan after 2 cycles of treatment (PET2) which will be centrally reviewed. The Deauville score from central review will be used to risk adapt subsequent therapy as follows: * Patients with Deauville score 1-3 will have one further cycle of their randomised chemotherapy and then enter follow up. * Patients with Deauville score 4 will have two further cycles of their randomised chemotherapy followed by involved site radiotherapy * Patients with Deauville score 5 will be withdrawn from trial treatment. They will have further treatment at their treating clinician's discretion and will enter follow up for the trial. Patients with Deauville score 4 on PET2 will have a final PET-CT scan to confirm adequate treatment response. Patients will be followed up for a minimum of 5 years after completing treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,042
Involved site radiotherapy as per International Lymphoma Radiation Oncology Group (ILROG) guidelines. Recommended dose 30Gy
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Stanford University - (Stanford Cancer Institute)
Stanford, California, United States
RECRUITINGUniversity of Miami School of Medicine
Miami, Florida, United States
RECRUITINGMemorial Sloan Kettering Cancer Center
New York, New York, United States
RECRUITINGRoyal North Shore Hospital
Saint Leonards, New South Wales, Australia
Progression free survival (PFS)
Time from randomisation to first date of progression or death
Time frame: 3 years from end of treatment
PET-CMR (complete metabolic response) rate
Proportion of patients who have Deauville score 1-3 on PET-CT scan
Time frame: At the end of cycle 2 (each cycle is 28 days)
Event-free survival (EFS)
Time from randomisation to first date of progression, death or a positive PET2 scan (whichever occurs first)
Time frame: 5 years from end of treatment
Overall survival (OS)
Time from randomisation to death
Time frame: 5 years from end of treatment
Incidence of second cancers and cardiovascular disease
Proportion in each arm who develop a second cancer or cardiovascular disease
Time frame: 5 years from end of treatment
Safety and toxicity of ABVD and A2VD as described by CTCAE v5.0
Numbers of patients experiencing a grade 3+ adverse event of each type will be presented and compared between the arms. Only patients who start treatment will be included
Time frame: From start of treatment to 30 days post treatment
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Townsville University Hospital
Townsville, Queensland, Australia
RECRUITINGRoyal Adelaide Hospital
Adelaide, Australia
RECRUITINGBox Hill Hospital
Box Hill, Australia
RECRUITINGRoyal Brisbane and Women's Hospital
Brisbane, Australia
RECRUITINGRoyal Darwin Hospital
Darwin, Australia
RECRUITINGLiverpool Hospital
Liverpool, Australia
RECRUITING...and 62 more locations