A Phase II Study of Ipilimumab in Combination With Carboplatin and Paclitaxel in Patients With Unresectable Stage III or Stage IV Melanoma
- Willing and able to give written informed consent.
- Histologic diagnosis of malignant melanoma
- Untreated unresectable Stage III melanoma with N3 macroscopic lymph nodes or
in-transit/satellite metastases or Stage IV melanoma (note that prior adjuvant
melanoma therapy is permitted). Prior treatment with BRAF inhibitors in the
metastatic setting is also permitted.
- Measurable/evaluable disease
- Required values for initial laboratory tests:
- WBC ≥ 2000/uL
- ANC ≥ 1.5 x 10E9/L
- Platelets ≥ 100 x 10E9/L
- Hemoglobin ≥ 90 g/L (may be transfused)
- Creatinine Clearance ≥ 50 ml/min (calculated -Cockcroft-Gault)
- AST/ALT ≤ 2.5 x ULN for patients without liver metastasis,
≤ 5 times for liver metastases
- Bilirubin ≤ 2.5 x ULN
- 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 26 weeks after the last dose of investigational product, in such a manner
that the risk of pregnancy is minimized.
WOCBP include any female who has experienced menarche and who has not undergone successful
surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy)
or is not post-menopausal. Post-menopause is defined as:
- Amenorrhea ≥ 12 consecutive months without another cause, or
- For women with irregular menstrual periods and taking hormone replacement therapy
(HRT), a documented serum follicle stimulating hormone (FSH) level ≥ 35 U/L. WOCBP
must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or
equivalent units of HCG) within 72 hours before the start of ipilimumab.
Men of fathering potential must be using an adequate method of contraception to avoid
conception throughout the study [and for up to 26 weeks after the last doseof
investigational product] in such a manner that the risk of pregnancy is minimized.
- Evidence of symptomatic CNS lesions as determined by the investigator (patients with
asymptomatic lesions or previously irradiated or surgically resected are eligible).
- Any other malignancy from which the patient has been disease-free for less than one
year, with the exception of adequately treated 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, 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).
- 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.
- Patients with ≥ Grade 2 peripheral neuropathy.
- 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 therapy with any of the following: IL 2, interferon, or other non-study
immunotherapy regimens; immunosuppressive agents; other investigation therapies; or
chronic use of systemic corticosteroids.
- Women of childbearing potential (WOCBP), defined above, who:
1. are unwilling or unable to use an acceptable method of contraception to avoid
pregnancy for their entire study period and for at least 26 weeks after
cessation of study drug, or
2. have a positive pregnancy test at baseline, or
3. are pregnant or breastfeeding.
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical (eg, infectious) illness.