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

AbbVie

Status and phase: Completed; Phase 2

Conditions: Melanoma; Skin Cancer; Metastatic Melanoma

Treatments: Other: Placebo; Drug: ABT-888; Drug: temozolomide

Study type: Interventional

Funder types: Industry

Identifiers

NCT00804908

M10-440

2008-004941-27 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 346 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 international normalized ratio (INR) < 1.5.
• Subject's with significant fluid retention may be allowed at the discretion of the investigator.
• 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 central nervous system metastases or leptomeningeal disease.
• Prior treatment with Dacarbazine (DTIC) or Temozolomide (TMZ).
• Prior DNA damaging agents or cytotoxic chemotherapy.
• Prior Whole Brain Radiation Therapy (with exceptions).
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

346 participants in 3 patient groups, including a placebo group

Placebo for ABT-888 BID + TMZ QD

Placebo Comparator group

Description:

Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.

Treatment:

Drug: temozolomide

Other: Placebo

ABT-888 20 mg BID + TMZ QD

Active Comparator group

Description:

ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.

Treatment:

Drug: temozolomide

Drug: ABT-888

ABT-888 40 mg BID + TMZ QD

Active Comparator group

Description:

ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.

Treatment:

Drug: temozolomide

Drug: ABT-888