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Trial Details
Trial status:
In set-up (funded)
Recruitment start date:
Funder:
Takeda Pharmaceutical Company Ltd
Sponsor:
UCL
Chief Investigator:
Prof John Radford
Recruitment target:
1042
EudraCT number:
2020-005160-65
Contact details:
ctc.radar@ucl.ac.uk
Lay summary:
RADAR
A randomised phase III trial with a PET response adapted design comparing ABVD +/- ISRT with A2VD +/- ISRT in patients with previously untreated stage IA/IIA Hodgkin lymphoma
Description
Design: Eligible patients will be randomised to either ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) or A2VD (doxorubicin, brentuximab vedotin, vinblastine, dacarbazine).

Patients will have a PET-CT scan after 2 cycles of treatment, which will be reviewed centrally. The outcome of this response assessment will be used to adapt the patient's treatment plan.
Patients with Deauville score 1-3 will have one further cycle of ABVD/A2VD
Patients with Deauville score 4 will have two further cycles of ABVD/A2VD followed by another PET-CT scan. As long as the patient does not have progressive disease, they will have involved site radiotherapy (ISRT)
Patients with Deauville score 5 will stop trial treatment and enter follow up. They will have further treatment for Hodgkin lymphoma off trial, at their treating clinician's discretion.

Patients will be followed up for a minimum of 5 years after completing treatment. They will have a scan (either CT or PET-CT, depending on the result of previous scans), and lung function tests 3 and 12 months after stopping treatment.

The following are optional exploratory elements of the trial; patients can enter the trial even if they do not wish to take part in these:
- PET-CT scan after cycle 1 
- Donating up to 10 sequential blood samples for laboratory studies to increase understanding of Hodgkin lymphoma
- Donating their diagnostic tumour block for laboratory studies to increase understanding of Hodgkin lymphoma
Treatment: ABVD (standard arm; 3-4 x 28 day cycles)

·        Doxorubicin 25mg/m2 IV, day 1 & 15

·        Bleomycin 10,000 IU/m2 IV, day 1 & 15

·        Vinblastine 6mg/m2 IV, day 1 & 15

·        Dacarbazine 375mg/m2 IV, day 1 & 15

A2VD (experimental arm; 3-4 x 28 day cycles)

·        Doxorubicin 25mg/m2 IV, day 1 & 15

·        Brentuximab Vedotin 1.2mg/kg (max 120mg) IV, day 1 & 15

·        Vinblastine 6mg/m2 IV, day 1 & 15

·        Dacarbazine 375mg/m2 IV, day 1 & 15

 ·       Filgrastim for 5-7 days from days 2 & 16        

Involved site radiotherapy (ISRT)

As per International Lymphoma Radiation Oncology Group guidelines (typical schedule 30Gy in 15 fractions)

Key inclusion/exclusion criteria:

Inclusion criteria:

1.      Males and females aged 16-69 years (inclusive)
2.     Histologically confirmed classical Hodgkin lymphoma
3.     Stage I or II with no mediastinal bulk disease or B-symptoms. Bulky disease at other sites is acceptable
4.     ECOG performance status 0-2
5.     No previous treatment for Hodgkin lymphoma
6.     Fit to receive anthracycline based chemotherapy
7.     Creatinine clearance (measured or calculated)>40ml/min
8.     Total bilirubin
9.     ALT or AST
10.  Adequate bone marrow function: Neutrophils ≥1.0 x 109/l, platelets ≥100 x 109/l
11.  Haemoglobin ≥8g/dl
12.  Willing and able to comply with the requirements of the protocol, including contraceptive advice where applicable
13. Written informed consent

Exclusion criteria:

1.     Previous treatment for Hodgkin lymphoma
2.     Nodular lymphocyte predominant Hodgkin lymphoma
3.     Absence of FDG-avid lymphoma lesions on baseline PET scan
4.     Age 70 years or over, or 15 years and under
5.     Other cancer diagnosed within the past 5 years apart from completely excised carcinoma in situ of any type and basal or squamous cell carcinoma of the skin
6.     Recurrent or persistent other cancer within the last 5 years irrespective of date of initial diagnosis
7.     Pre-existing sensory or motor peripheral neuropathy from any cause, grade 1
8.     History of, or current progressive multi-focal leukoencephalopathy or other chronic condition of the brain
9.     Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
10.  Infection with HIV, hepatitis C or active hepatitis B infection (surface antigen or DNA positive)
11.  Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics, antivirals or antifungals within 2 weeks prior to first study drug dose
12.  Receiving or recently treated with any other investigational agent (within 4 weeks of study entry)
13.  Pregnant or breastfeeding women
14.   Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin or any component of ABVD
15. Known history of any cardiovascular or respiratory conditions that would preclude anthracycline or bleomycin administration
16. Other significant medical or psychiatric comorbidity that in the opinion of the investigator would make administration of ABVD or A2VDhazardous

Duration of recruitment: 5 years (expected June 2021-May 2026)
Aim

To assess whether substituting A2VD for ABVD as part of a PET-response adapted design in early stage HL can:

  • Improve progression free survival (primary endpoint)
  • Improve complete metabolic remission (CMR) rate
  • Improve overall survival
  • Decrease late toxicity by reducing the proportion of patients receiving RT and thereby the incidence of second cancers and cardiovascular disease
  • Eliminate pulmonary toxicity
Trial protocols
Trial protocols must not be applied to patients treated outside trials. UCL CTC can only ensure that approved trial investigators are provided with amendments to protocols.
No protocols have been currently made available for download
Trial documents
No documents have been currently made available for download
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