A Dose Escalation Phase I Study of Radiotherapy Administered in Combination With Anti-CTLA4 Monoclonal Antibody (Ipilimumab) in Patients With Unresectable Stage III or Stage IV Advanced Malignant Melanoma
- Willing and able to give written informed consent.
- Histologic diagnosis of melanoma.
- Unresectable locally advanced or metastatic melanoma with at least one melanoma
metastasis accessible to radiation therapy.
- Measurable disease according to immune related Response Criteria
- Required values for initial laboratory tests:
WBC >= 2000/uL ANC >= 1000/uL Platelets >= 75 x 103/uL Hemoglobin >= 8 g/dL Creatinine <=
2,5 x ULN AST/ALT <= 2.5 x ULN for patients without liver metastasis or <= 5 x ULN for
patients with liver metastasis Total Bilirubin <= 1,5.x ULN, (except patients with
Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
- No active or chronic infection with HIV, Hepatitis B, or Hepatitis C.
- ECOG Performance status of 0 or 1.
- Men and women, >= 18 years of age.
- Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study and for up to 8 weeks after the
last dose of investigational product, in such a manner that the risk of pregnancy is
- Suspected or known CNS tumors including brain metastasis.
- Any other malignancy form which the patient has been disease-free for less than 5
years, with the exception of adequately treated and cured basal or squamous cell skin
cancer, superficial bladder cancer or carcinoma in situ of the cervix.
- Autoimmune disease: Patients with a history of inflammatory bowel disease are
excluded from this study, as are patients with a history of symptomatic disease
(e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic
lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor
neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome).
- Any underlying medical or psychiatric condition, which in the opinion of the
investigator will make the administration of ipilimumab hazardous or obscure the
interpretation of AEs, such as a condition associated with frequent diarrhea.
- Any non-oncology vaccine therapy used for prevention of infectious diseases (for up
to 1 month before or after any dose of ipilimumab).
- A history of prior treatment with ipilimumab or prior CD137 agonist or CTLA‑4
inhibitor or agonist.
- Concomitant hormonal treatment, chemotherapy or immunotherapy.
- Other investigational therapy.
- Prior radiotherapy within the same body area.
- Prior radiotherapy targeting fields containing flat bones.
- Women of childbearing potential (WOCBP), defined above
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical (e.g., infectious) illness.
- Persons of reproductive potential must agree to use an adequate method of
contraception throughout treatment and for at least 8 weeks after ipilimumab is