20TiP - Phase I trial of stereotactic body radiotherapy with concurrent fixed dose ipilimumab in metastatic melanoma: Dose limiting toxicity and abscopal ef...

Date 20 November 2015
Event ESMO Symposium on Immuno-Oncology 2015
Session Welcome reception and general Poster viewing
Topics Cancer Immunology and Immunotherapy
Melanoma and other Skin Tumours
Surgery and/or Radiotherapy of Cancer
Presenter Katrien De Wolf
Citation Annals of Oncology (2015) 26 (suppl_8): 5-14. 10.1093/annonc/mdv514
Authors K. De Wolf1, P. Ost2, V. Kruse3, L. Brochez4, I. Chevolet4
  • 1Radiotherapy, Gent University Hospital, 9000 - Gent/BE
  • 2Radiotherapy-oncology, Gent University Hospital, 9000 - Gent/BE
  • 3Medical Oncology, Gent University Hospital, 9000 - Gent/BE
  • 4Dermatology, Gent University Hospital, 9000 - Gent/BE

Abstract

Background

The prognosis of metastatic melanoma remains poor although, for a subset of patients, a breakthrough has been achieved with ipilimumab. Unfortunately, due to immune resistance, the majority of patients do not obtain long-lasting clinical benefit. Radiotherapy (RT) is able to interfere with immune resistance on different levels and preclinical evidence clearly indicates that combining RT with anti-CTLA-4 treatment increases response rates compared to single agent treatment. These data are supported by several spectacular clinical cases and one retrospective study. We hypothesize that combining ipilimumab with RT will result in a higher response rate compared to either treatment alone. Aim: - To determine the maximum tolerated dose and recommended dose of stereotactic body radiotherapy (SBRT) given concurrent with ipilimumab to patients with metastatic melanoma. - To evaluate the immune response of the combination therapy. - To describe any preliminary evidence of anti-tumor activity by assessment of objective response in non-irradiated metastases at 12 weeks.

Trial design

A phase I trial in patients with metastatic melanoma. The largest PET-positive metastasis with a correlate on CT will be chosen as radiotherapeutic target. In this trial the dose of ipilimumab will be fixed and the dose of SBRT will be escalated in 3 dose levels, which will allow us to gain insights on the effect of dose per fraction on immune response. The dose escalation will start at 24 Gy (8 Gy per fraction), followed by 30 Gy (10 Gy per fraction) and 36 Gy (12 Gy per fraction).

Prior to the radiotherapy, patients will receive 2 cycles of ipilimumab on day 1 and day 21, afterwards patients will receive radiotherapeutic treatment on day 36, 39 an 41. The third cycle of ipilimumab will be administrated on day 42 followed by the fourth cycle of ipilimumab on day 63.

A total of 18 patients will be included.

Treatment modality d1 d21 d36 d39 d41 d42 d63 d84
ipilimumab 1st cycle 2nd cycle 3th cycle 4th cycle
SBRT 1st fraction 2nd fraction 3th fraction
Evaluation 1st evaluation PET-CT

Clinical trial identification

Clinical trial identifiction:

- ClinicalTrials.gov identifier: NCT02406183
- Ethical comittee identifier: EC 2015/0025

Disclosure

All authors have declared no conflicts of interest.