Back to resultsA Study Evaluating Efficacy of ABT-888 in Combination With Temozolomide in Metastatic Melanoma
Primary Purpose
Melanoma, Metastatic Melanoma, Skin Cancer
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
temozolomide
ABT-888
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Melanoma focused on measuring Temozolomide, Skin cancer, Melanoma, Metastatic Melanoma, ABT-888, MM
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Active Comparator
Active Comparator
Arm Label
Placebo for ABT-888 BID + TMZ QD
ABT-888 20 mg BID + TMZ QD
ABT-888 40 mg BID + TMZ QD
Arm 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.
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.
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.
Outcomes
Primary Outcome Measures
Progression-Free Survival (PFS): Time to Event
PFS: the number of days from the date that the participant was randomized to the date the participant experienced a confirmed event of disease progression (radiological, as determined by the central imaging center; or clinical, as determined by the investigator), or to the date of death (all causes of mortality) if disease progression was not reached. All events were included whether the participant was still taking or had discontinued study drug. Events of death were included for participants who had not experienced a confirmed event of disease progression, provided the death occurred within 8 weeks of the last available disease progression assessment. The distribution of PFS, as determined by the central imaging center (radiological)/ investigator (clinical), was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% confidence intervals (95% CIs) for the quartiles for the PFS distribution are provided.
Secondary Outcome Measures
Overall Survival (OS): Time to Event
OS was defined as the number of days from the date the participant was randomized to the date of death. All deaths were included, whether the participant was still taking or had discontinued study drug. If a participant had not died and was lost to follow-up, then data were censored at the last study visit or contact date, or date the participant was last known to be alive, whichever was later; if the participant was not lost to follow-up, then data were censored at the last study visit or contact date, whichever was later. The distribution of OS was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the OS distribution are provided. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ groups were statistically significantly better than the Placebo + TMZ group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints.
12-Month Overall Survival (OS) Rate
The 12-month overall survival rate was defined as the percentage of participants surviving at 12 months. The distribution of 12-month OS rate was estimated using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the PFS distribution are provided. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.
6-month Progression-Free Survival Rate
The 6-month progression-free survival rate was defined as the percentage of participants without disease progression at 6 months.The distribution of 6-month progression-free survival rate, as determined by the central imaging center (radiological)/ investigator (clinical), was estimated using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the PFS distribution are provided. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.
Objective Response Rate
The objective response rate was defined as the percentage of participants with a confirmed CR or PR per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by computed tomography (CT) scan: complete response (CR), disappearance of all target lesions; partial response (PR), ≥30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.
Time to Disease Progression
The distribution of time to disease progression, as determined by the central imaging center (radiological)/ investigator (clinical), was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the PFS distribution are provided. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.
Disease Control Rate
The disease control rate was defined as the percentage of participants who had at least stable disease (complete response, partial response, or stable disease) through the end of Week 8. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.
Time to Neurological/Brain Metastases Progression
Time to neurological/brain metastases progression, defined as the number of days from the date of randomization to the date the participant experienced an event of neurological/brain metastases progression, was estimated using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the distribution are provided. All events of progression were included, regardless of whether the event occurred while the participant was still taking study drug. If a participant did not experience an event, data were censored at the date of the last available brain CT scan. For participants with no postbaseline brain CT scans, data were censored at randomization. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ groups were statistically significantly better than the Placebo + TMZ group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.
Full Information
NCT ID
NCT00804908
First Posted
December 1, 2008
Last Updated
May 2, 2018
Sponsor
AbbVie (prior sponsor, Abbott)
1. Study Identification
Unique Protocol Identification Number
NCT00804908
Brief Title
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
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie (prior sponsor, Abbott)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma, Metastatic Melanoma, Skin Cancer
Keywords
Temozolomide, Skin cancer, Melanoma, Metastatic Melanoma, ABT-888, MM
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
346 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo for ABT-888 BID + TMZ QD
Arm Type
Placebo Comparator
Arm 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.
Arm Title
ABT-888 20 mg BID + TMZ QD
Arm Type
Active Comparator
Arm 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.
Arm Title
ABT-888 40 mg BID + TMZ QD
Arm Type
Active Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
temozolomide
Other Intervention Name(s)
Temodar, Temodal
Intervention Description
temozolomide capsule administered orally once daily for 5 days every 28 days
Intervention Type
Drug
Intervention Name(s)
ABT-888
Other Intervention Name(s)
veliparib
Intervention Description
ABT-888 capsule administered orally twice daily for 7 days every 28 days
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo for ABT-888 capsule administered orally twice daily for 7 days every 28 days
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS): Time to Event
Description
PFS: the number of days from the date that the participant was randomized to the date the participant experienced a confirmed event of disease progression (radiological, as determined by the central imaging center; or clinical, as determined by the investigator), or to the date of death (all causes of mortality) if disease progression was not reached. All events were included whether the participant was still taking or had discontinued study drug. Events of death were included for participants who had not experienced a confirmed event of disease progression, provided the death occurred within 8 weeks of the last available disease progression assessment. The distribution of PFS, as determined by the central imaging center (radiological)/ investigator (clinical), was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% confidence intervals (95% CIs) for the quartiles for the PFS distribution are provided.
Time Frame
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 Outcome Measure Information:
Title
Overall Survival (OS): Time to Event
Description
OS was defined as the number of days from the date the participant was randomized to the date of death. All deaths were included, whether the participant was still taking or had discontinued study drug. If a participant had not died and was lost to follow-up, then data were censored at the last study visit or contact date, or date the participant was last known to be alive, whichever was later; if the participant was not lost to follow-up, then data were censored at the last study visit or contact date, whichever was later. The distribution of OS was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the OS distribution are provided. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ groups were statistically significantly better than the Placebo + TMZ group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints.
Time Frame
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.
Title
12-Month Overall Survival (OS) Rate
Description
The 12-month overall survival rate was defined as the percentage of participants surviving at 12 months. The distribution of 12-month OS rate was estimated using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the PFS distribution are provided. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.
Time Frame
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.
Title
6-month Progression-Free Survival Rate
Description
The 6-month progression-free survival rate was defined as the percentage of participants without disease progression at 6 months.The distribution of 6-month progression-free survival rate, as determined by the central imaging center (radiological)/ investigator (clinical), was estimated using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the PFS distribution are provided. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.
Time Frame
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.
Title
Objective Response Rate
Description
The objective response rate was defined as the percentage of participants with a confirmed CR or PR per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by computed tomography (CT) scan: complete response (CR), disappearance of all target lesions; partial response (PR), ≥30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.
Time Frame
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.
Title
Time to Disease Progression
Description
The distribution of time to disease progression, as determined by the central imaging center (radiological)/ investigator (clinical), was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the PFS distribution are provided. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.
Time Frame
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.
Title
Disease Control Rate
Description
The disease control rate was defined as the percentage of participants who had at least stable disease (complete response, partial response, or stable disease) through the end of Week 8. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.
Time Frame
Week 8
Title
Time to Neurological/Brain Metastases Progression
Description
Time to neurological/brain metastases progression, defined as the number of days from the date of randomization to the date the participant experienced an event of neurological/brain metastases progression, was estimated using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the distribution are provided. All events of progression were included, regardless of whether the event occurred while the participant was still taking study drug. If a participant did not experience an event, data were censored at the date of the last available brain CT scan. For participants with no postbaseline brain CT scans, data were censored at randomization. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ groups were statistically significantly better than the Placebo + TMZ group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.
Time Frame
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AbbVie Inc
Organizational Affiliation
AbbVie
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
26202595
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.
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A Study Evaluating Efficacy of ABT-888 in Combination With Temozolomide in Metastatic Melanoma
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