Metastatic Melanoma Clinical Trial
Official title:
Phase II Randomized Trial of Ipilimumab Versus Ipilimumab and Radiotherapy in Metastatic Melanoma
An attractive area of research regards immune manipulations to recover some of the patient's immune response to his/her tumor, a strategy that has the advantages of being both natural and potentially long-lasting.[1] We propose to combine immunotherapy with radiotherapy directed to a metastatic site, to create a "hub" for in vivo immunization to the tumor, to enable "tumor rejection" at the other metastatic sites. This "in vivo immunization" is explored as a viable alternative to an individualized vaccine approach. Preclinical data generated by us and others support a "proof of principle" clinical trial that may open the field to an alternative use of radiotherapy in a novel partnership with cancer immunotherapy.[2]
In addition, we propose to perform immune-monitoring of the patients accrued to the trial to
generate important information for hypothesis-driven research about the mechanisms behind the
clinical findings, to be tested in the laboratory.
An attractive area of research regards immune manipulations to recover some of the patient's
immune response to his/her tumor, a strategy that has the advantages of being both natural
and potentially long-lasting.[1] We propose to combine immunotherapy with radiotherapy
directed to a metastatic site, to create a "hub" for in vivo immunization to the tumor, to
enable "tumor rejection" at the other metastatic sites. This "in vivo immunization" is
explored as a viable alternative to an individualized vaccine approach. Preclinical data
generated by us and others support a "proof of principle" clinical trial that may open the
field to an alternative use of radiotherapy in a novel partnership with cancer
immunotherapy.[2]
In addition, we propose to perform immune-monitoring of the patients accrued to the trial to
generate important information for hypothesis-driven research about the mechanisms behind the
clinical findings, to be tested in the laboratory.
The specific aims of the study are:
1. To explore the induction of immunity-mediated tumor response outside the radiation field
(abscopal effect) after radiation/Ipilimumab in metastatic melanoma, by estimating and
comparing response rates in patients treated with Ipilimumab alone (Arm A) versus
ipilimumab and radiation (Arm B).
2. To compare the induction of a T-cell response in patients with metastatic melanoma
treated with either ipilimumab alone or in combination with radiation.
All patients with metastatic melanoma with at least 2 measurable sites of disease are
eligible. Extent of metastatic disease is recorded by CT scanning or MRI before therapy.
Patients will then be randomized to Ipilimumab 3 mg/kg IV over 90 minutes alone versus
Ipilimumab 3 mg/kg IV over 90 minutes plus radiotherapy to one of their measurable lesions, 6
Gy delivered daily x 5 days (Monday through Friday) (conformally or by IMRT/IGRT, to
maximally spare normal tissue), for a total of 30 Gy. For patients assigned to the
Ipilimumab/RT arm, Ipilimumab treatment starts after radiotherapy, with a dose given on day 4
from the first radiotherapy fraction. All patients will then have ipilimumab infusions
repeated on Days 25, 46 and 67. Patients will be re-imaged (CT imaging or MRI) on Week 12 and
evaluated for response (defined as an objective response of another metastatic site outside
the radiation field).
The main immunological end-point will be the induction or boosting of treatment induced T
cells (CD4+ and CD8+) and B cells for defined antigen approaches. In addition, the magnitude
and duration of T- and B-cell responses will be examined. Treatment-induced responses will be
calculated as the difference between the pre-treatment measurement and the measurement at the
different time points at which blood will be collected (time of evaluation) in the same
patient. The percentage of patients with the induction of treatment-induced T- and B-cell
responses will be reported.
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