- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00804908
A Study Evaluating Efficacy of ABT-888 in Combination With Temozolomide in Metastatic Melanoma
May 2, 2018 updated by: AbbVie (prior sponsor, Abbott)
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
346
Phase
- Phase 2
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo for ABT-888 BID + TMZ QD
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.
|
temozolomide capsule administered orally once daily for 5 days every 28 days
Other Names:
Placebo for ABT-888 capsule administered orally twice daily for 7 days every 28 days
|
Active Comparator: ABT-888 20 mg BID + TMZ QD
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.
|
temozolomide capsule administered orally once daily for 5 days every 28 days
Other Names:
ABT-888 capsule administered orally twice daily for 7 days every 28 days
Other Names:
|
Active Comparator: ABT-888 40 mg BID + TMZ QD
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.
|
temozolomide capsule administered orally once daily for 5 days every 28 days
Other Names:
ABT-888 capsule administered orally twice daily for 7 days every 28 days
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-Free Survival (PFS): Time to Event
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.
|
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.
|
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 Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS): Time to Event
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.
|
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.
|
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.
|
12-Month Overall Survival (OS) Rate
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.
|
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.
|
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.
|
6-month Progression-Free Survival Rate
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.
|
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.
|
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.
|
Objective Response Rate
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.
|
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.
|
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.
|
Time to Disease Progression
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.
|
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.
|
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.
|
Disease Control Rate
Time Frame: Week 8
|
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.
|
Week 8
|
Time to Neurological/Brain Metastases Progression
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.
|
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.
|
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.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
February 1, 2009
Primary Completion (Actual)
January 1, 2016
Study Completion (Actual)
January 1, 2016
Study Registration Dates
First Submitted
December 1, 2008
First Submitted That Met QC Criteria
December 8, 2008
First Posted (Estimate)
December 9, 2008
Study Record Updates
Last Update Posted (Actual)
June 6, 2018
Last Update Submitted That Met QC Criteria
May 2, 2018
Last Verified
March 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Melanoma
- Skin Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Poly(ADP-ribose) Polymerase Inhibitors
- Temozolomide
- Veliparib
Other Study ID Numbers
- M10-440
- 2008-004941-27 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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