Clinical trial NCT00804908: A Study Evaluating Efficacy of ABT-888 in Combination With Temozolomide in Metastatic Melanoma
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Evaluating the Efficacy of ABT-888 in Combination With Temozolomide Versus Temozolomide Alone in Subjects With Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma
Metastatic Melanoma
Skin Cancer
Keywords: Temozolomide
Skin cancer
Melanoma
Metastatic Melanoma
ABT-888
MM
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2008-12-09
Enrollment: 346
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-Free Survival (PFS): Time to Event
timeFrame: Every Cycle (28 Days) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.
Secondary outcomes:
measure: Overall Survival (OS): Time to Event
timeFrame: Per protocol, survival follow-up information was to be obtained every 3 months for up to 18 months after the final visit for the subject. The maximum observed follow-up at the overall survival analysis time was 21.0 months.
measure: 12-Month Overall Survival (OS) Rate
timeFrame: Per protocol, survival was to be assessed every 4 weeks or as needed after participant is registered as off-study for up to 18 months. The maximum observed follow-up at the overall survival analysis time was 21.0 months.
measure: 6-month Progression-Free Survival Rate
timeFrame: Every Cycle (28 Days) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.
measure: Objective Response Rate
timeFrame: Every 2 cycles (8 weeks) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.
measure: Time to Disease Progression
timeFrame: Every Cycle (28 Days), until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.
measure: Disease Control Rate
timeFrame: Week 8
measure: Time to Neurological/Brain Metastases Progression
timeFrame: Every 2 cycles (8 weeks) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: AbbVie Inc
role: STUDY_DIRECTOR
References:
citation: Middleton MR, Friedlander P, Hamid O, Daud A, Plummer R, Falotico N, Chyla B, Jiang F, McKeegan E, Mostafa NM, Zhu M, Qian J, McKee M, Luo Y, Giranda VL, McArthur GA. Randomized phase II study evaluating veliparib (ABT-888) with temozolomide in patients with metastatic melanoma. Ann Oncol. 2015 Oct;26(10):2173-9. doi: 10.1093/annonc/mdv308. Epub 2015 Jul 22.