A Phase I Study of Intralesional Bacillus Calmette-Guerin (BCG) and Followed by Ipilimumab Therapy in Patients With Advanced Metastatic Melanoma
- Histologically confirmed stage III (unresectable) or stage IV melanoma
- Minimum one metastatic lesion, cutaneous or subcutaneous, but ideally three or more
lesions, to accommodate IL injection (1 lesion), accessibility for biopsy (1 lesion),
and evaluability for response by RECIST v.1.1 (1 lesion) and modified RECIST (irRC).
- Performance status of ECOG 0-1
- Within the last 2 weeks prior to study day 1, vital laboratory parameters should be
within normal range, except for the following laboratory parameters, which should be
within the ranges specified:
Haemoglobin: ≥ 100 g/L, Platelets: ≥ 100 x 10^9/L, INR: ≤ 2.0, Creatinine: ≤ 120 µmol/L,
Bilirubin: ≤ 30 µmol/L, eGFR: > 0.75 x LLN, ALT/AST: ≤ 2.0 x ULN, Albumin: > 28 g/L,
Neutrophils: > 1.5 x 10^9/L, Lymphocytes: > 0.9 x 10^9/L,
- Active cerebral metastases unless stable after radiation for at least one month and
not requiring corticosteroid treatment for 30 days prior to enrolment
- Other known malignancy within 3 years prior to entry into the study, except for
treated non-melanoma skin cancer and cervical carcinoma in situ.
- History of tuberculosis
- History of hypersensitivity to BCG
- Any contraindication to the use of isoniazid
- Generalized skin disease
- Autoimmune disease: Patients with a history of inflammatory bowel disease, including
ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients
with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive
sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg,
Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g.
Guillain-Barre Syndrome and Myasthenia Gravis). Exceptions: vitiligo, type I
diabetes, pernicious anaemia (treated).
- 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.
- Prior immunotherapy or systemic adjuvant therapy for melanoma following most recent
relapse and/or resection of melanoma
- Prior treatment with a CTLA4 inhibitor
- Concomitant therapy with any of the following: IL-2, interferon, or other non-study
immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other
investigation therapies; or chronic use of systemic corticosteroids
- Known HIV positivity, Hepatitis B or Hepatitis C
- Chemotherapy or radiation therapy within the preceding 4 weeks (6 weeks for
- Lack of availability for immunological and clinical follow-up assessments.
- articipation in any other clinical trial involving another investigational agent
within 4 weeks prior to first dosing.
- Mental impairment that may compromise the ability to give informed consent and to
comply with the requirements of the study.
- Women who are pregnant (positive pregnancy test at baseline), or breastfeeding
- Men and women unwilling or unable to use an acceptable method of contraception to
avoid pregnancy for their entire study period and for at least 8 weeks after
cessation of study drug.
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical (e.g., infectious) illness.