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Brentuximab Vedotin in Early-Stage Hodgkin Lymphoma, RADAR Trial
Trial Status: active
This phase III trial compares the effect of doxorubicin (also known as Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD regimen) to brentuximab vedotin (also known as Adcetris) with doxorubicin (Adriamycin), vinblastine and dacarbazine (A^2VD regimen) for the treatment of early-stage Hodgkin lymphoma. Chemotherapy drugs, such as doxorubicin, bleomycin, vinblastine and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. The usual approach for treatment in patients with Hodgkin lymphoma, the ABVD regimen, is sometimes followed by radiotherapy. A majority of patients are cured with the standard treatment. Although the usual approach will cure most patients, doctors would like to increase the number of patients cured and reduce the chance of the disease coming back (a relapse). The A^2VD regimen may be effective in shrinking or stabilizing early-stage Hodgkin lymphoma.
Stage I or II supradiaphragmatic disease with no mediastinal bulk disease (defined as greater than a third of the transthoracic diameter at any level of thoracic vertebrae as determined by CT) or B symptoms. Bulky disease at other sites is acceptable. Extranodal disease (single extranodal site [stage I] or contiguous extranodal extension [stage II]) is acceptable
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
No previous treatment for Hodgkin lymphoma
Fit to receive anthracycline based chemotherapy (patients with a history of ischaemic heart disease or hypertension should have a left ventricular ejection fraction of ≥ 50%)
Creatinine clearance (measured or calculated) > 40 ml/min
Total bilirubin < 1.5 x upper limit of normal, unless attributable to disease or known Gilbert’s syndrome
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2 x the upper limit of normal
Neutrophils ≥ 1.0 x10^9/l
Platelets ≥ 100 x10^9/l
Haemoglobin ≥ 8 g/dL
Willing and able to comply with the requirements of the protocol, including contraceptive advice, where applicable
Written informed consent
Exclusion Criteria
Previous treatment for Hodgkin lymphoma, excluding short courses of oral corticosteroids at a dose of up to 100 mg prednisolone (or equivalent) for up to 7 days
Infradiaphragmatic disease
Nodular lymphocyte predominant Hodgkin lymphoma
Absence of FDG-avid lymphoma lesions on baseline PET scan
Age 70 years or over or age 15 years or under
Other cancer diagnosed within the last 5 years. Patients with completely excised carcinoma in situ of any type and basal or squamous cell carcinoma of the skin are not excluded
Recurrent or persistent other cancer within last 5 years irrespective of date of initial diagnosis
Pre-existing grade ≥1 sensory or motor peripheral neuropathy from any cause
History of or current progressive multi-focal leukoencephalopathy or other chronic condition of the brain
Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
Infection with HIV, hepatitis C or active hepatitis B infection (surface antigen or DNA positive)
Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to first trial drug dose
Receiving or recently treated with any other investigational agent (within 4 weeks of trial entry)
Pregnant or breastfeeding women
Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin or any component of ABVD
Known history of any cardiovascular or respiratory conditions that would preclude anthracycline or bleomycin administration
Other significant medical or psychiatric co-morbidity that in the opinion of the investigator would make administration of ABVD or A^2VD hazardous
Additional locations may be listed on ClinicalTrials.gov for NCT04685616.
Locations matching your search criteria
United States
California
Palo Alto
Stanford Cancer Institute Palo Alto
Status: Active
Contact: Ranjana Hira Advani
Phone: 650-498-6000
Florida
Coral Gables
UM Sylvester Comprehensive Cancer Center at Coral Gables
I. To assess whether the substitution of bleomycin (ABVD) to brentuximab vedotin (A^2VD) improves progression free survival (PFS).
SECONDARY OBJECTIVES:
I. To assess whether the substitution of bleomycin (ABVD) to brentuximab vedotin (A^2VD) improves positron emission tomography (PET) complete metabolic response (CMR) rates.
II. To assess whether the substitution of bleomycin (ABVD) to brentuximab vedotin (A^2VD) improves event-free survival (EFS).
III. To assess whether the substitution of bleomycin (ABVD) to brentuximab vedotin (A^2VD) has an effect on overall survival (OS).
IV. To assess whether the substitution of bleomycin (ABVD) to brentuximab vedotin (A^2VD) has an effect on the subsequent need for radiotherapy.
V. To assess whether the substitution of bleomycin (ABVD) to brentuximab vedotin (A^2VD) has an effect on the incidence of second cancers and cardiovascular disease.
VI. To assess the safety and toxicity of ABVD and A^2VD.
EXPLORATORY OBJECTIVES:
I. To evaluate the prognostic power of PET after 1 and 2 cycles of ABVD/A^2VD with European Organization for Research and Treatment of Cancer (EORTC) and German Hodgkin Study Group (GHSG) pre-treatment risk factors.
II. To evaluate the prognostic value of baseline metabolic tumour volume and/or tumour lesion glycolysis compared to treatment response after PET2 and whether imaging patterns and uptake in tumour and non-tumour tissues on PET-computed tomography (CT) can predict response and side-effects to brentuximab vedotin and chemotherapy.
III. To investigate whether a quantitative extension to the Deauville score provides a better assessment of response for individual patients than the 5-point ordinal scale.
IV. To refine PET-CT reading and interpretation including exploration of automated methods for measurement of fludeoxyglucose F-18 (FDG) uptake and radiomic features, and improvements in image registration.
V. To assess whether the substitution of bleomycin (ABVD) to brentuximab vedotin (A^2VD) has an effect on pulmonary function tests.
VI. To assess the relationship between maximum tumour dimension at baseline and end of treatment with PFS.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive doxorubicin intravenously (IV), bleomycin IV, vinblastine IV, and dacarbazine IV on days 1 and 15 of each cycle. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET-CT scan between days 24 and 27 of cycle 1 (optional) and cycle 2 (mandatory). Patients with a Deauville score of 1-3 after PET-CT receive 1 additional cycle of treatment. Patients with Deauville score of 4 after PET-CT receive an additional 2 cycles of treatment and undergo involved-site radiation therapy (ISRT). Patients with Deauville score of 5 discontinue study treatment. Patients also undergo collection of blood samples throughout the trial and echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) as clinically indicated.
ARM B: Patients receive doxorubicin IV, brentuximab vedotin IV over 30 minutes, vinblastine, and dacarbazine IV on days 1 and 15 of each cycle. Patients also receive filgrastim subcutaneously (SC) for 5-7 days from day 2 and day 16 of each cycle. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET-CT scan between days 24 and 27 of cycle 1 (optional) and cycle 2 (mandatory). Patients with a Deauville score of 1-3 after PET-CT receive 1 additional cycle of treatment. Patients with Deauville score of 4 after PET-CT receive an additional 2 cycles of treatment and undergo ISRT. Patients with Deauville score of 5 discontinue study treatment. Patients also undergo collection of blood samples throughout the trial and ECHO or MUGA as clinically indicated.
After completion of study treatment, patients are followed up at months 1, 3, 6, 9, and 12, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.
Trial PhasePhase III
Trial Typetreatment
Lead OrganizationUniversity of Miami Miller School of Medicine-Sylvester Cancer Center
