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A Trial of ABI-007 Versus Dacarbazine in Previously Untreated Patients With Metastatic Malignant Melanoma

Phase 3
Completed
Conditions
Malignant Melanoma
Interventions
Registration Number
NCT00864253
Lead Sponsor
Celgene
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
529
Inclusion Criteria
  • Histologically or cytologically confirmed cutaneous malignant melanoma with evidence of metastasis (Stage IV).
  • No prior cytotoxic chemotherapy for metastatic malignant melanoma is permitted. Prior treatment with kinase inhibitors or cytokines is permitted.
  • No prior adjuvant cytotoxic chemotherapy is permitted. Prior adjuvant therapy with interferon, Granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or vaccines is permitted.
  • Male or non-pregnant and non-lactating female, and ≥ 18 years of age. If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative serum pregnancy test Beta human chorionic gonadotropin (ß-hCG) within 72 hours prior to first study drug administration. If sexually active, the patient must agree to utilize contraception considered adequate and appropriate by the investigator.
  • No other current active malignancy within the past 3 years.
  • Radiographically-documented measurable disease (defined by the presence of at least 1 radiographically documented measurable lesion
  • Patient has the following blood counts at Baseline:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9 cells/L;
  • platelets ≥ 100 x 10^9 cells/L;
  • Hemoglobin (Hgb) ≥ 9 g/dL.
  • Patient has the following blood chemistry levels at Baseline:
  • Aspartate aminotransferase(AST) glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) ≤ 2.5x upper limit of normal range (ULN); ≤ 5.0 xULN if hepatic metastases present;
  • total bilirubin ≤ ULN;
  • creatinine ≤ 1.5 mg/dL.
  • Lactate Dehydrogenase (LDH) ≤ 2.0 x ULNa
  • Expected survival of > 12 weeks.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  • Patient or his/her legally authorized representative or guardian has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent form prior to participation in any study-related activities.
Exclusion Criteria
  • History of or current evidence of brain metastases, including leptomeningeal involvement.
  • Patient has pre-existing peripheral neuropathy of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Scale of Grade ≥ 2.
  • Prior radiation to a target lesion is permitted only if there has been clear progression of the lesion since radiation was completed.
  • Patient has a clinically significant concurrent illness.
  • Patient is, in the investigator's opinion, unlikely to be able to complete the study through the End of Study (EOS) visit.
  • Patient is currently enrolled, or will enroll in a different clinical study in which investigational therapeutic procedures are performed or investigational therapies are administered while participating in this study. Marker studies or studies evaluating biological correlates are permitted.
  • Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ABI-007ABI-007Treatment Arm A (ABI-007): 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.
DacarbazineDacarbazineTreatment Arm B (dacarbazine): 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.
Primary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS) Based on a Blinded Radiology Assessment of Response Using Response Evaluation Criteria in Solid Tumors (RECIST) GuidelinesResponse assessment completed every 8 weeks until disease progression for up to 106 weeks; data cut off 30 June 2012

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.

Secondary Outcome Measures
NameTimeMethod
Participant SurvivalUp to 38 months; Up to data cut off of 30 June 2012

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.

Nadir for Platelet Count Measurements.Day 1 up to 106 weeks; up to data cut off 30 June 2012

Maximal degree of myelosuppression was represented by the nadir in platelet count measurements over all treatment cycles.

Pharmacokinetic ParametersOn Cycle 1, Day 1 blood samples were taken at 0.25, 3.5, and 24 hr post-infusion end of the initial dose
Number of Participants Experiencing Dose Reductions, or Dose Interruptions, or Dose Delays of Study DrugMaximum study drug exposure 106 weeks; data cut off 30 June 2012

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.

Nadir for White Blood Cells (WBCs) MeasurementsDay 1 up to 106 weeks; up to data cut off 30 June 2012

Maximal degree of myelosuppression was represented by the nadir in white blood cells (WBCs) count measurements over all treatment cycles.

Summary of Treatment-emergent Adverse Events (AEs)Maximum exposure to study drug was 106 weeks; up to data cut off of 30 June 2012

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.

Nadir for the Absolute Neutrophil Count (ANC) MeasurementsDay 1 up to 106 weeks; up to data cut off 30 June 2012

Maximal degree of myelosuppression during study drug dosing was represented by the nadir in ANC measurements over all treatment cycles.

Nadir for the Hemoglobin Count MeasurementsDay 1 up to 106 weeks; up to data cut off 30 June 2012

Maximal degree of myelosuppression during study drug dosing was represented by the nadir in hemoglobin count measurements over all treatment cycles.

Trial Locations

Locations (111)

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

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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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States

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