Clinical Investigation of Proton Treatment in Hodgkin Lymphoma Patients - PRO-Hodgkin

Official title

Clinical Investigation of PBS Proton Treatment in Hodgkin Lymphoma Patients - PRO-Hodgkin

Overview

Hodgkin Lymphoma patients with limited stage are commonly cured with limited chemotherapy followed by radiotherapy. Studies have shown a risk of late toxicity from the radiotherapy, such as second cancer, heart failure and lung toxicity. With proton therapy the dose to normal tissue can be minimised without compromising the dose to the tumor. The aim of our study is to investigate whether proton therapy can be delivered in a safe way to Hodgkin Lymphoma patients with less late side effects than conventional radiotherapy, while retaining the high cure rate. This is a multicentre phase II study of PBS proton beam therapy in patients ≤60 years, with early stage Hodgkin Lymphoma treated with induction chemotherapy. The study is performed in a non-inferiority setting comparing with a historical population-based consecutive Swedish material. The control group was treated according to the same principles, except that the radiotherapy was delivered with photons.

Interventions

• Radiation Proton therapy.
  Pencil beam scanning proton therapy to a dose of 20 or 29.75 Gy (RBE) after standard chemotherapy (2-4 ABVD).

Primary outcome measures

• Progression free survival (PFS) [Time frame: Outcome will be measured after 1, 3, 5 and 16 years.]

Secondary outcome measures (8)

• Overall survival (OS) [Time frame: Outcome will be measured after 1, 3, 5 and 16 years.]
• Time to progression (TTP) [Time frame: Outcome will be measured after 1, 3, 5 and 16 years.]
• Absorbed dose to organs at risk. [Time frame: Outcome will be measured at baseline.]
• Patterns of failure. [Time frame: Outcome will be measured after 1, 3, 5 and 16 years.]
• Acute adverse events. [Time frame: Outcome will be measured within 3 months.]
• Long-term adverse events. [Time frame: Outcome will be measured after 1, 3, 5 and 16 years.]
• Quality of life. [Time frame: Outcome will be measured after 1, 3, 5 and 16 years.]
• Quality of life. [Time frame: Outcome will be measured after 1, 3, 5 and 16 years.]

Eligibility criteria

Inclusion criteria

• Histological diagnosis of classic Hodgkin Lymphoma.
• Ann Arbour stage 1A, 1B or 2A.
• Both patients with and without risk factors, i.e. bulky disease, erythrocyte sedimentation rate (ESR)>50, more than two involved sites.
• Supra diaphragmal disease.
• Age 18-60 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
• Initial staging positron emission tomography/computed tomography (PET/CT).
• Induction chemotherapy including 2 cycles of ABVD for patients without risk factors and 4 cycles of ABVD for patients with risk factors.
• For patients with risk factors a CT after 2 ABVD confirming complete remission (CR) or partial remission (PR). For patients without risk factors clinical response is sufficient at inclusion, but a CT scan is recommended before start of radiotherapy.
• Radiotherapy (RT) start not later than 6 weeks after end of chemotherapy.
• Written informed consent obtained prior to any study specific procedures.
• Women of reproductive age must agree to use contraceptives during the study treatment period.

Exclusion criteria

• Pregnancy.
• Serious concomitant systemic disorder endangering treatment delivery.
• More than 5mm tumour motion on 4 dimensional computed tomography (4DCT) unless deep inspiration breath hold (DIBH) is used. Not applicable if target is located outside mediastinum or photon treatment is planned.
• Clinical or radiographic stable disease (SD)/ progressive disease (PD) during induction chemotherapy.
• Not able to comply with treatment and study procedures.
• No additional active malignancy except indolent lymphoma in the bone marrow, basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ cervical cancer.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Sweden · 6 centers

• Sahlgrenska University Hospital — Gothenburg
• Skane University Hospital — Lund
• Orebro University Hospital — Örebro
• Karolinska University Hospital — Solna
• Umea University Hospital — Umeå
• Uppsala University Hospital — Uppsala

Publications

• Specht L, Yahalom J, Illidge T, Berthelsen AK, Constine LS, Eich HT, Girinsky T, Hoppe RT, Mauch P, Mikhaeel NG, Ng A; ILROG. Modern radiation therapy for Hodgkin lymphoma: field and dose guidelines from the international lymphoma radiation oncology group (ILROG). Int J Radiat Oncol Biol Phys. 2014 Jul 15;89(4):854-62. doi: 10.1016/j.ijrobp.2013.05.005. Epub 2013 Jun 18. PMID 23790512
• Maraldo MV, Dabaja BS, Filippi AR, Illidge T, Tsang R, Ricardi U, Petersen PM, Schut DA, Garcia J, Headley J, Parent A, Guibord B, Ragona R, Specht L. Radiation therapy planning for early-stage Hodgkin lymphoma: experience of the International Lymphoma Radiation Oncology Group. Int J Radiat Oncol Biol Phys. 2015 May 1;92(1):144-52. doi: 10.1016/j.ijrobp.2014.12.009. Epub 2015 Feb 7. PMID 25670544
• Aznar MC, Maraldo MV, Schut DA, Lundemann M, Brodin NP, Vogelius IR, Berthelsen AK, Specht L, Petersen PM. Minimizing late effects for patients with mediastinal Hodgkin lymphoma: deep inspiration breath-hold, IMRT, or both? Int J Radiat Oncol Biol Phys. 2015 May 1;92(1):169-74. doi: 10.1016/j.ijrobp.2015.01.013. Epub 2015 Mar 5. PMID 25754634
• Petersen PM, Aznar MC, Berthelsen AK, Loft A, Schut DA, Maraldo M, Josipovic M, Klausen TL, Andersen FL, Specht L. Prospective phase II trial of image-guided radiotherapy in Hodgkin lymphoma: benefit of deep inspiration breath-hold. Acta Oncol. 2015 Jan;54(1):60-6. doi: 10.3109/0284186X.2014.932435. Epub 2014 Jul 15. PMID 25025999
• Hoppe BS, Flampouri S, Su Z, Morris CG, Latif N, Dang NH, Lynch J, Li Z, Mendenhall NP. Consolidative involved-node proton therapy for Stage IA-IIIB mediastinal Hodgkin lymphoma: preliminary dosimetric outcomes from a Phase II study. Int J Radiat Oncol Biol Phys. 2012 May 1;83(1):260-7. doi: 10.1016/j.ijrobp.2011.06.1959. Epub 2011 Oct 17. PMID 22014950
• Hoppe BS, Flampouri S, Su Z, Latif N, Dang NH, Lynch J, Joyce M, Sandler E, Li Z, Mendenhall NP. Effective dose reduction to cardiac structures using protons compared with 3DCRT and IMRT in mediastinal Hodgkin lymphoma. Int J Radiat Oncol Biol Phys. 2012 Oct 1;84(2):449-55. doi: 10.1016/j.ijrobp.2011.12.034. Epub 2012 Mar 2. PMID 22386373
• Hoppe BS, Flampouri S, Zaiden R, Slayton W, Sandler E, Ozdemir S, Dang NH, Lynch JW, Li Z, Morris CG, Mendenhall NP. Involved-node proton therapy in combined modality therapy for Hodgkin lymphoma: results of a phase 2 study. Int J Radiat Oncol Biol Phys. 2014 Aug 1;89(5):1053-1059. doi: 10.1016/j.ijrobp.2014.04.029. Epub 2014 Jun 10. PMID 24928256
• Hoppe BS, Hill-Kayser CE, Tseng YD, Flampouri S, Elmongy HM, Cahlon O, Mendenhall NP, Maity A, McGee LA, Plastaras JP. Consolidative proton therapy after chemotherapy for patients with Hodgkin lymphoma. Ann Oncol. 2017 Sep 1;28(9):2179-2184. doi: 10.1093/annonc/mdx287. PMID 28911093

Identifiers

NCT: NCT06883604 · 2019-00010

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗