A Study Evaluating Efficacy of ABT-888 in Combination With Temozolomide in Metastatic Melanoma

• Overall Survival [ Time Frame: Every 4 weeks or as needed after subject is registered as off-study, up to 18 months ] [ Designated as safety issue: No ]
• 12-month Survival Rate [ Time Frame: Every cycle (28 days) ] [ Designated as safety issue: No ]
• 6-month Progression Free Survival Rate [ Time Frame: Every cycle (28 days) ] [ Designated as safety issue: No ]
• Time to Disease Progression [ Time Frame: Every cycle (28 days) ] [ Designated as safety issue: No ]

• Overall survival [ Time Frame: Subject death ] [ Designated as safety issue: No ]
• 12-month survival rate [ Time Frame: Every cycle (28 days) ] [ Designated as safety issue: No ]
• 6-month progression free survival rate [ Time Frame: Every cycle (28 days) ] [ Designated as safety issue: No ]
• Time to disease progression [ Time Frame: Every cycle (28 days) ] [ Designated as safety issue: No ]

The purpose of this study is to evaluate the efficacy of ABT-888 in combination with temozolomide versus temozolomide alone in subjects with metastatic melanoma.

• Melanoma
• Metastatic Melanoma
• Skin Cancer

• Drug: temozolomide
  150 mg/m2 temozolomide daily for 5 days every 28 days
  Other Name: Temodar, Temodal
• Drug: ABT-888
  Either 20 mg or 40 mg BID for 7 days every 28 days
• Drug: Placebo
  Placebo BID for 7 days every 28 days

• Active Comparator: 1
  TMZ + ABT-888 at 20 mg BID
  Interventions:

  • Drug: temozolomide
  • Drug: ABT-888
• Active Comparator: 2
  TMZ + ABT-888 at 40 mg BID
  Interventions:

  • Drug: temozolomide
  • Drug: ABT-888
• Placebo Comparator: 3
  TMZ + Placebo
  Interventions:

  • Drug: temozolomide
  • Drug: Placebo

Inclusion Criteria:

• Histologically (or cytologically) confirmed metastatic melanoma.
• Unresectable Stage III or Stage IV metastatic melanoma.
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• Subjects with no history of brain metastases demonstrated by a baseline MRI,or subjects with a history of previously treated brain metastases who have history of operable/SRS treatable brain metastases and completed surgical resection/stereotactic radiosurgery with or without adjuvant whole brain radiation at least 28 days prior to Day 1.
• have baseline MRI that shows no evidence of active intercranial disease
• have discontinued taking medications for symptom management of brain metastases at least 7 days prior to Day 1
• 28 days since prior anti-cancer therapy.
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1.
• Adequate hematologic, renal and hepatic function.
• Partial Thromboplastin Time (PTT) is <= 1.5 x upper normal limit of institution's normal range and INR < 1.5.
• Subject's with significant fluid retention may be allowed at the discretion of the PI.
• Life expectancy > 12 weeks.
• Females must not be pregnant.
• Voluntarily signed informed consent.

Exclusion Criteria:

• Lactate Dehydrogenase (LDH) > 2 x Upper Limit of Normal (ULN).
• Ocular malignant melanoma.
• History of CNS metastases or leptomeningeal disease.
• Prior treatment with Dacarbazine (DTIC) or Temozolomide (TMZ).
• Prior DNA damaging agents or cytotoxic chemotherapy.
• Prior Whole Brain Radiation Therapy.
• Received an investigational agent within 28 days of study.
• History of seizure disorder and/or taking medication for seizure disorder.
• Active malignancy within the past 5 years, except cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin.
• Medical condition that would cause a high risk for toxicities.