RADVAX: A Stratified Phase I/II Dose Escalation Trial of Stereotactic Body Radiotherapy Followed by Ipilimumab in Metastatic Melanoma

Stratified phase I/II study of escalating fractions of stereotactic body radiotherapy combined with immunotherapy for previously untreated/previously treated metastatic melanoma patients. Phase I is stratified by site: bone/lung versus liver/subcutaneous. Phase II is stratified by prior treatment: previously untreated versus previously treated. In phase II, 14 patients will be treated at the maximum tolerated dose (MTD) in each stratum of which phase I patients treated at the site specific MTD will be included.

This is a stratified phase I/II study of escalating fractions of stereotactic body radiotherapy (SBRT) combined with immunotherapy with Ipilimumab for previously untreated or previously treated metastatic melanoma patients who are aged 18 years or older. Phase I is stratified by site: bone or lung versus liver or subcutaneous (s.c.) Six patients will be enrolled per dose cohort. Phase II is stratified by prior treatment:previously untreated for metastatic disease versus previously treated for metastatic disease. In phase II, 14 patients will be treated at the MTD (maximum tolerated dose) in each stratum of which phase I patients treated at the site specific MTD will be included. Descriptive statistics will be generated for both phases of the study.

• Drug: Ipilimumab
• Radiation: Stereotactic Body Radiation Therapy

• Experimental: Phase 1
  Interventions:

  • Drug: Ipilimumab
  • Radiation: Stereotactic Body Radiation Therapy
• Experimental: Phase 2
  Interventions:

  • Drug: Ipilimumab
  • Radiation: Stereotactic Body Radiation Therapy

Inclusion Criteria:

• Patients aged 18 years and older.
• Histologically confirmed diagnosis of melanoma
• Previously treated or previously untreated stage IV melanoma by AJCC staging criteria
• Presence of an index lesion between 1 cm and 5 cm.
• EGOC performance status 0 to 1
• Signed informed consent document.
• Adequate renal, hepatic, and hematologic indices for ipilimumab therapy
• Ability to tolerate stereotactic body radiation therapy (e.g. lie flat and hold position for treatment)

Exclusion Criteria:

• Prior systemic therapy within 28 days of study enrollment
• Clinical contraindication to stereotactic body radiotherapy (e.g.active systemic sclerosis, active inflammatory bowel disease if bowel is within target field, etc)
• Previous treatment with antiCTLA-4 antibody or cancer vaccine
• Presence or history of central nervous system metastasis (including brain)
• Long-term use of systemic corticosteroids
• Prior RT within 2 months of study entry