The main purpose of this research study is to compare the safety, tolerability, and anti tumor activity of an investigational drug, ABI-007 versus Dacarbazine in patients with metastatic melanoma who have not previously received chemotherapy. ABI-007 is a new preparation of the active drug paclitaxel. It contains the same medication as the prescription chemotherapy drug Abraxane®. Abraxane® is approved by the FDA for the treatment of metastatic breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Dacarbazine is approved by the FDA for the treatment of melanoma. In this study, ABI-007 and Dacarbazine will be tested as therapy for people who have not yet had any cancer treatment for the diagnosis of metastatic melanoma.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
529
Patients who receive ABI-007 will be dosed intravenously over approximately 30 minutes without steroid pre-medication and without G-CSF prophylaxis (unless modified as described below). ABI-007 150 mg/m2 will be administered on Days 1, 8, and 15 every 4 weeks.
Patients who receive dacarbazine will be dosed intravenously at 1000 mg/m2 on Day 1 with steroid and antiemetic pre-medication. Treatment will be repeated every 21 days.
University of Alabama at Birmingham
Birmingham, Alabama, United States
AZ Cancer Ctr
Scottsdale, Arizona, United States
Arizona Cancer Center
Tucson, Arizona, United States
Genesis Cancer Ctr - Hot Springs
Hot Springs, Arkansas, United States
University of Arkansa for Medical Sciences
Little Rock, Arkansas, United States
Progression Free Survival (PFS) Based on a Blinded Radiology Assessment of Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines
PFS was defined as the time from the randomization date to the start of disease progression or patient death, whichever occurred first. Participants who did not have disease progression or had not died were censored at the last known time that the patient was progression free. In the event of palliative radiotherapy or surgery, they were censored at the last assessment where they were documented to be progression-free prior to the date of radiotherapy or surgery. In follow up, participants who began new anticancer therapy prior to documented progression were censored at the last assessment where they were documented as progression free. Those with two or more missing response assessments prior to a visit with documented disease progression (or death) were censored at the last visit where they were documented to be progression free. RECIST defines progressive disease as a ≥ 20% increase taking as reference the smallest sum of the longest diameters recorded since the treatment began.
Time frame: Response assessment completed every 8 weeks until disease progression for up to 106 weeks; data cut off 30 June 2012
Participant Survival
Survival was defined as the time from the date of randomization to the date of death (any cause). Participants were censored at the last known time that they were alive.
Time frame: Up to 38 months; Up to data cut off of 30 June 2012
Summary of Treatment-emergent Adverse Events (AEs)
A Treatment Emergent AE (TEAE) was any AE that began or worsened after the start of the study drug through 30 days after the last dose of study drug or end of study whichever is later. A treatment related toxicity was one considered by the investigator to be possibly, probably or definitely related to study drug. AE's were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V 3.0 criteria and the following scale: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life threatening, and Grade 5 = Death A SAE is any untoward medical occurrence at any dose that is fatal or life threatening, results in persistent or significant disability or incapacity; requires prolonged hospitalizations; is a congenital anomaly birth defect in the offspring of a patient, and conditions not included in the above that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.
Time frame: Maximum exposure to study drug was 106 weeks; up to data cut off of 30 June 2012
Number of Participants Experiencing Dose Reductions, or Dose Interruptions, or Dose Delays of Study Drug
The number of participants with dose reductions, dose interruptions and dose delays that occurred during the treatment period. Dose reductions, interruptions and delays are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.
Time frame: Maximum study drug exposure 106 weeks; data cut off 30 June 2012
Nadir for the Absolute Neutrophil Count (ANC) Measurements
Maximal degree of myelosuppression during study drug dosing was represented by the nadir in ANC measurements over all treatment cycles.
Time frame: Day 1 up to 106 weeks; up to data cut off 30 June 2012
Nadir for White Blood Cells (WBCs) Measurements
Maximal degree of myelosuppression was represented by the nadir in white blood cells (WBCs) count measurements over all treatment cycles.
Time frame: Day 1 up to 106 weeks; up to data cut off 30 June 2012
Nadir for Platelet Count Measurements.
Maximal degree of myelosuppression was represented by the nadir in platelet count measurements over all treatment cycles.
Time frame: Day 1 up to 106 weeks; up to data cut off 30 June 2012
Nadir for the Hemoglobin Count Measurements
Maximal degree of myelosuppression during study drug dosing was represented by the nadir in hemoglobin count measurements over all treatment cycles.
Time frame: Day 1 up to 106 weeks; up to data cut off 30 June 2012
Pharmacokinetic Parameters
Time frame: On Cycle 1, Day 1 blood samples were taken at 0.25, 3.5, and 24 hr post-infusion end of the initial dose
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Tower Cancer Research Foundation
Beverly Hills, California, United States
San Diego Pacific Oncology and Hematology Associates
Encinitas, California, United States
Loma Linda University Cancer Center
Loma Linda, California, United States
University of Southern California/Norris Cancer Center
Los Angeles, California, United States
University of CA Los Angeles
Los Angeles, California, United States
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