Comparison of High-dose IL-2 and High-dose IL-2 With Radiation Therapy in Patients With Metastatic Melanoma. (SBRT/IL-2)

The purpose of this study is compare the response rates in patients with metastatic melanoma treated with high-dose IL-2 to patients treated with high-dose IL-2 along with radiation therapy.

All patients will receive high-dose IL-2. Half the patients enrolled will be randomly selected to receive radiation therapy to up to three tumors prior to receiving high-dose IL-2. Among the first 20 patients enrolled, those assigned to receive radiation will receive a single dose of radiation and for patients 21-44, those assigned to receive radiation will receive 2 doses of radiation.

• Other: Radiation therapy and high-dose IL-2
  Patients 1 - 20 will receive a single fraction of radiation. Patients 21 through the completion of the study will receive two fractions. The dose for all patients will be 20 Gy per fraction to the prescription line at the edge of the planning treatment volume (PTV) with the last dose delivered on a Friday before IL-2 administration. For patients receiving two radiation doses, the doses can be administered on the Wednesday and Friday before IL-2 starts. Patients who are assigned to IL-2 monotherapy and have progressive disease after two IL-2 cycles are then eligible to receive SBRT before cycle 3 of IL-2 commences, single fraction for patients 1-20 and two fractions for patients 21- end of study.
  Other Names:

  • Interleukin 2
  • Stereotactic Body Radiation Therapy (SBRT)
• Drug: High-dose IL-2
  IL-2 will be given on a Monday at a dose of 600,000 IU per kilogram IV every 8 hours for up to 14 doses each cycle. The second cycle is planned 16 days after cycle 1 but may be delayed up to one week to allow toxicity to resolve. The maximum number of doses that can be given during two cycles will be 28 doses. Patients who respond after two cycles can receive 4 more cycles of IL-2. Patients with disease progression after 2 cycles may elect to receive radiation before a 3rd cycle of IL-2. If patients crossover, IL-2 will be given on the Monday following the last dose of radiation, at a dose of 600,000 IU per kilogram IV every 8 hours for a maximum of 14 doses each cycle. Another cycle is planned 16 days after cycle 3 but may be delayed up to one week to allow toxicity to resolve.
  Other Names:

  • Interleukin 2
  • Stereotactic Body Radiation Therapy (SBRT).

• Active Comparator: High-dose IL-2
  Patients receive standard high-dose IL-2 therapy, with an opportunity to crossover to the experimental arm if there is disease progression noted after two cycles of high-dose IL-2.
  Intervention: Drug: High-dose IL-2
• Experimental: Radiation therapy and high-dose IL-2
  Patients 1-20 who are assigned to receive radiation therapy will receive a single dose of radiation before IL-2; patients 21-44 assigned to receive radiation will receive two doses of radiation before receiving high-dose IL-2.
  Intervention: Other: Radiation therapy and high-dose IL-2

Inclusion Criteria:

• Histological confirmation of melanoma will be required by previous biopsy or cytology.
• Patients must be ≥ 18 years of age.
• Patients must have tumors amenable to SBRT in lungs, mediastinum, chest wall, bones (other than long bones), or liver (inclusive of immediately adjacent masses), 1 - 3 foci; no minimum size, but none greater than 7 cm. Patients may have other metastases but only a maximum of 3 will be treated.
• ECOG performance status of 0-1.
• Women of childbearing potential must have a serum or urine pregnancy test performed within 72 hours prior to the start of protocol treatment. The results of this test must be negative in order for the patient to be eligible. In addition, women of childbearing potential as well as male patients must agree to take appropriate precautions to avoid pregnancy.
• Patients must sign a study-specific consent form.

Exclusion Criteria:

• No metastatic site amenable to SBRT.
• Patients with brain metastases not candidates for radiosurgery.
• Previous radiation to sites proposed for radiation as part of this study.
• Patients with active systemic, pulmonary, or pericardial infection.
• Pregnant or lactating women.
• Evidence of ischemia on exercise tolerance test, stress thallium study, or baseline EKG.
• DLCO, FEV1 or FEV1/FVC less than 70% of predicted due to clinically significant underlying pulmonary disease. For any pulmonary function test values less than predicted values, the PI will review, and document the patient's suitability for high dose IL-2 therapy.
• WBC < 3.0 x 109/L
• Hgb < 9.0 g/dL
• AST/ALT > 3 times the upper limit of the normal range
• total bilirubin > 1.9 g/dL
• creatinine > 1.9 g/dL
• Patient requires chronic steroids.