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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University College London

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Apr 2024 → ongoing

Decision date (initial)

2023-07-19

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Takeda Development Center Americas, Inc.

External identifiers

EU CT number

2022-500031-37-00

ClinicalTrials.gov

NCT04685616

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Others, Safety

To assess whether substituting A2VD for ABVD as part of a PET-response adapted design in early stage HL can: improve the Progression Free Survival (PFS)

Secondary objectives 11

1. Prognostic value of baseline metabolic tumour volume and/or tumour lesion glycolysis on PET
2. Prognostic power of PET after 1 & 2 cycles of ABVD/A2VD compared with EORTC and GHSG pre-treatment risk factors
3. Prognostic power of PET after 1 and 2 cycles using a quantitative extension to the Deauville score
4. Correlate response to treatment and side-effects with radiomic features on PET-CT
5. Evaluate the use of automated methods to measure uptake in and segment tumour and non-tumour tissue on FDG PET-CT scans
6. Change in pulmonary function tests
7. Relationship between maximum tumour dimension at baseline and end of treatment with PFS
8. Improve the PET Complete Metabolic Response (CMR) rate
9. Improve the Overall Survival (OS)
10. Decrease the late toxicity by reducing the proportion of patients receiving radiotherapy (RT) and the incidence of second cancers and cardiovascular disease
11. Improve Event Free Survival (EFS)

Conditions and MedDRA coding

​ stage IA/IIA Hodgkin lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Males and females age 16-69 years (inclusive).
2. Histologically confirmed classical Hodgkin lymphoma
3. 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.
4. ECOG performance status 0-2
5. No previous treatment for Hodgkin lymphoma
6. 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%)
7. Creatinine clearance (measured or calculated) >40 ml/min
8. Total bilirubin < 1.5 x upper limit of normal, unless attributable to disease or known Gilbert’s syndrome
9. ALT or AST < 2 x the upper limit of normal
10. Adequate bone marrow function with neutrophils ≥1.0x10exp9/l and platelets ≥100 x10exp9/l
11. Haemoglobin ≥ 80 g/L (equivalent to ≥ 4.96mmol/L)
12. Willing and able to comply with the requirements of the protocol, including contraceptive advice, where applicable
13. Written informed consent

Exclusion criteria 15

1. Previous treatment for Hodgkin lymphoma, excluding short courses of oral corticosteroids at a dose of up to 100mg prednisolone (or equivalent) for up to 7 days
2. Known infection with HIV, hepatitis C or active hepatitis B infection (surface antigen or DNA positive)
3. Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics, antivirals or antifungals within 2 weeks prior to first study drug dose
4. Receiving or recently treated with any other investigational agent (within 4 weeks of study entry)
5. Pregnant or breastfeeding women
6. Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin or any component of ABVD
7. Known history of any cardiovascular or respiratory conditions that would preclude anthracycline or bleomycin administration
8. Other significant medical or psychiatric co-morbidity that in the opinion of the investigator would make administration of ABVD or A2VD hazardous
9. Infradiaphragmatic disease
10. Nodular lymphocyte predominant Hodgkin lymphoma
11. Absence of FDG-avid lymphoma lesions on baseline PET scan
12. Age 70 years or over, or 17 years and under
13. Other active cancer (new, relapsed or persistent) within the last 5 years with the exception of: a) Prostate cancer meeting the following criteria: • Gleason grade group 1 (Gleason score ≤ 6) being managed with active surveillance. • Previously treated more than 1 year ago with radical prostatectomy and undetectable PSA, or definitive radiation therapy and PSA <2 and stable or falling. b) Skin cancers meeting the following criteria:• Completely excised carcinoma in situ of any type and basal or squamous cell carcinoma of the skin c.) Other cancers meeting the following criteria: • Treated 5 or more years ago with no recurrence since that time
14. Pre-existing sensory or motor peripheral neuropathy from any cause, grade ≥1
15. History of or current progressive multi-focal leukoencephalopathy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-Free Survival (PFS)

Secondary endpoints 5

1. PET Complete Metabolic Response (CMR) rate after 2 cycles of ABVD/ A2VD
2. Event-Free Survival (EFS)
3. Overall survival (OS)
4. Incidence of second cancers and cardiovascular disease
5. Safety and toxicity of ABVD and A2VD as assessed by CTCAE v5.0

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Comparator 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University College London

Sponsor organisation

University College London

Address

Gower Street

City

London

Postcode

WC1E 6BT

Country

United Kingdom

Scientific contact point

Organisation

University College London

Contact name

Darren Edwards

Public contact point

Organisation

University College London

Contact name

Nick McNally

Third parties 5

Locations

7 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 81 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications