Single-Arm Phase II Study of the Evaluation of Stereotactic Body Radiation Therapy Concurrent With Nelfinavir for Oligometastases
The use of radiation therapy to treat metastatic tumors is well established and promising
data are emerging with the use of SBRT for metastatic disease. However, the use of a single
large fraction concurrent with a radiosensitizer as is being proposed is not of proven
benefit. This investigation aims to confirm the safety and efficacy for SBRT used
concurrently with a radiosensitizer in the setting of oligometastatic disease. The dose
selected has been chosen with the belief that it is safe and effective based on prior
experience with SBRT of lung cancer, pancreatic cancer and brain radiosurgery. All patients
will be treated with a single fraction, targeted to the lesion concurrently with the
On the basis of this preclinical evidence, we propose a phase I-II study of nelfinavir
combined with SBRT in patients with oligometastatic disease. Because the standard dose of
nelfinavir for HIV patients is known to be safe and does inhibit the phosphorylation of Akt
and decrease tumor hypoxia, we propose to study this in conjunction with a 15 Gy dose of
SBRT. One primary end point is to evaluate the toxicity of nelfinavir in concurrent use
with SBRT. The second is to determine the efficacy of nelfinavir in concurrent use with
SBRT. Combined positron emission tomography (PET) and computed tomography (CT) imaging
using RECIST (Response Evaluation Criteria in Solid Tumors) criteria will be used to
evaluate the response of the patients.
Experience with single-fraction pulmonary and pancreas SBRT provides a useful dose for this
trial. With published data establishing the relative safety of large single-fraction SBRT to
the lungs and pancreas, we have decided to proceed to determine the safety of 15 Gy SBRT
concurrently with the radiosensitizer nelfinavir. Once this is established, we propose to
continue to enroll more patients to the study at this dose to determine the efficacy of this
type of therapy.
In general metastatic disease carries an extremely high mortality rate. Current therapies
provide only partial palliation of symptoms and mild to moderate prolongation of survival.
Patients are rarely cured of this disease; consequently, better treatment is clearly needed.
The proposed treatment represents a logical extension of the current state-of-the-art
radiation therapy. It has the potential to translate into more effective palliation and
longer patient survival. Another advantage to the patient is that several weeks of
radiation therapy can be accomplished in a single day, which is not inconsequential for
patients with a limited life expectancy.
The proposed study represents an informed estimate based on current knowledge of SBRT doses
and those administered in currently approved image-guided protocols (brain, base of skull,
cervico-thoracic spine, pancreas and liver). This study will refine the current
understanding of single fraction radiation tolerance for normal tissues, thereby making it
possible to treat future patients more safely and aggressively.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To document the number of participants that do not have progression at the 6 months post treatment time frame
To determine the 6-month progression free survival rate of the radiosensitizer nelfinavir used concurrently with 15 Gy of stereotactic body radiation therapy (SBRT) delivered in 1 fraction in patients with oligometastatic disease.
Stephanie Terezakis, M.D.
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
United States: Food and Drug Administration
|The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231|