MedPath

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)

Loma Linda University Cancer Center

🇺🇸

Loma Linda, California, United States

Mary Crowley Research Center

🇺🇸

Dallas, Texas, United States

Royal Adelaide Hospital, Department of Medical Oncology

🇦🇺

Adelaide, South Australia, Australia

Sydney West Cancer Trials Centre/Westmead Hospital

🇦🇺

Westmead, New South Wales, Australia

Royal North Shore Hospital

🇦🇺

Sydney, New South Wales, Australia

BC Cancer Agency-Fraser Valley Ctr.

🇨🇦

Surrey, British Columbia, Canada

CHRU Hopital Claude Huriez

🇫🇷

Lile Cedax, France

Hopital de 1 Archet 2

🇫🇷

Nice Cedex 3, France

Royal Perth Hospital

🇦🇺

Perth, Western Australia, Australia

BCCA Centre for the Southern Interior

🇨🇦

Kelowna, British Columbia, Canada

The Ottawa Hospital Regional Cancer Centre

🇨🇦

Ottawa, Ontario, Canada

Hopital Bichat

🇫🇷

Paris, France

London Regional Cancer Program

🇨🇦

London, Ontario, Canada

IST-Istituto Nazionale per la Ricera sul Cancro

🇮🇹

Genova, GE, Italy

Hopital Sainte Marguerite

🇫🇷

Marseille Cedex 9, France

Sunnybrook Health Sciences Centre

🇨🇦

Toronto, Ontario, Canada

CHU Hopital Saint Eloi

🇫🇷

Montepellier Cedex 5, France

Universitaetsklinkum Tuebingen

🇩🇪

Tuebingen, BW, Germany

Universitaetklinkum Koeln

🇩🇪

Koln, Northwest, Germany

Royal Hobart Hospital

🇦🇺

Hobart, Tasmania, Australia

Centre Leon Berad

🇫🇷

Lyon, France

Medizinische Hochschuke Hannover

🇩🇪

Hannover, NI, Germany

Azienda Ospedaliera Universitaria Sense

🇮🇹

Siena, SI, Italy

Credit Valley Hospital

🇨🇦

Missiauga, Ontario, Canada

Hopital Dypuytren-CHU de Limoges

🇫🇷

Limoges cedex, France

Univ Hospital of North Staffordshire

🇬🇧

Stroke On Kent, Staffs, United Kingdom

H Clinic i Provincial

🇪🇸

Barcelona, Spain

Hopital Saint-Louis

🇫🇷

Paris Cedex, France

Nottingham University Hospitals NHS Trust

🇬🇧

Nottingham, Nott, United Kingdom

Universitaetsklinkum Dresden

🇩🇪

Dresden, SN, Germany

St. Josef-Hospital

🇩🇪

Bochum, Northwest, Germany

Royal Marsden Hospital London

🇬🇧

London, United Kingdom

Universitaetsklinkum Hamburg-Eppendorf

🇩🇪

Hamburg, HH, Germany

Rijnstate ziekenhuis Arnhem

🇳🇱

Amhem, Netherlands

Hopital Saint Andre' CHU de Bordeaux

🇫🇷

Bordeaux, France

Singleton Hospital, Sothwest Wales Inst.

🇬🇧

Swansea, S Glam, United Kingdom

Newcross Hospital

🇬🇧

Wolverhampton, Wstmid, United Kingdom

H Clinico San Carlos

🇪🇸

Madrid, Spain

Universitaetsklinkum Essen

🇩🇪

Essen, Northwest, Germany

UniversitawtsklinKum Jena

🇩🇪

Jena, Strasse 35, Germany

Istituto Europeo di Oncologia

🇮🇹

Milano, MI, Italy

St. George's Hospital

🇬🇧

London, GT Lon, United Kingdom

Universitaetsklinkum Heidelberg

🇩🇪

Heidelber, BW, Germany

H CLINIC I Provincial

🇪🇸

Barcelona, Spain

Universitaetsklinkum Wuerzburg PS

🇩🇪

Wuerzburg, BY, Germany

Charite Universitaetsmedizin Berlin

🇩🇪

Berlin, BE, Germany

Corporacion Sanitaria Parc Tauli

🇪🇸

Sabadell, Spain

Medisch Centrum Alkmaar

🇳🇱

Alkmaar, Netherlands

Velindre Hospital

🇬🇧

Cardiff, Glam, United Kingdom

Sir Charles Gairdner Hospital

🇦🇺

Nedlands Perth, Western Australia, Australia

Broomfield Hospital

🇬🇧

Chelmsford, Essex, United Kingdom

Tower Cancer Research Foundation

🇺🇸

Beverly Hills, California, United States

San Diego Pacific Oncology and Hematology Associates

🇺🇸

Encinitas, California, United States

University of CA Los Angeles

🇺🇸

Los Angeles, California, United States

University of Southern California/Norris Cancer Center

🇺🇸

Los Angeles, California, United States

Baptist Cancer Institute

🇺🇸

Jacksonville, Florida, United States

University of Colorado Cancer Center

🇺🇸

Aurora, Colorado, United States

University of Miami Hospital and Clincs/SCCC

🇺🇸

Miami, Florida, United States

Lakeland Regional Cancer Center

🇺🇸

Lakeland, Florida, United States

Waren Billhartz Cancer Center

🇺🇸

Maryville, Illinois, United States

Indiana University

🇺🇸

Indianapolis, Indiana, United States

IA Blood and Cancer Care, PLC

🇺🇸

Cedar Rapids, Iowa, United States

Beth Israel Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

Saint Louis University

🇺🇸

Saint Louis, Missouri, United States

St. John's Medical Research

🇺🇸

Springfield, Missouri, United States

Atlantic Melanoma Center

🇺🇸

Morristown, New Jersey, United States

Piedmont Hematology

🇺🇸

Winston-Salem, North Carolina, United States

OH State University Arthur G. James Cancer Hospital

🇺🇸

Columbus, Ohio, United States

St. Luke's Hospital & Health Network

🇺🇸

Bethlehem, Pennsylvania, United States

Thomas Jefferson University

🇺🇸

Philadelphia, Pennsylvania, United States

Univ of TX MD Anderson Cancer Ctr

🇺🇸

Houston, Texas, United States

Univ of TX Med School at Houston

🇺🇸

Houston, Texas, United States

Covenant Health System DBA Joe Arrington Cancer Research and Treatment Center

🇺🇸

Lubbock, Texas, United States

Hope Oncology

🇺🇸

Richardson, Texas, United States

Univ. of Washington Medical Center/Seattle Cancer Care Alliance

🇺🇸

Seattle, Washington, United States

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Evergreen Hematology & Oncology

🇺🇸

Spokane, Washington, United States

Port Macquarie Base Hospital

🇦🇺

Port Macquarie, New South Wales, Australia

St. Mary's Medical Center

🇺🇸

San Francisco, California, United States

Wayne State University

🇺🇸

Detroit, Michigan, United States

Integris Cancer Institute of OK

🇺🇸

Oklahoma City, Oklahoma, United States

Utah Cancer Specialist

🇺🇸

Salt Lake City, Utah, United States

Istituto Tumori "Giovanni Paolo II"

🇮🇹

Bari, BA, Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei T

🇮🇹

Meldola, FC, Italy

Istituto Nazionale Tumori

🇮🇹

Milano, MI, Italy

IOV-Instituto Oncologico IRCCS

🇮🇹

Padova, PD, Italy

Ist. Naz. per lo studio e la cura dei tumori G. Pascale

🇮🇹

Napoli, Italy

Ospedale S. Chiara

🇮🇹

Pisa, Italy

Genesis Cancer Ctr - Hot Springs

🇺🇸

Hot Springs, Arkansas, United States

Arizona Cancer Center

🇺🇸

Tucson, Arizona, United States

Tom Baker Cancer Centre

🇨🇦

Calgary, Alberta, Canada

Centre Hospitaller Universitaire de Grenoble

🇫🇷

Grenoble Cedex 09, France

Centre Regional Val d' Aurelle Paul Lamarque

🇫🇷

Montpellier, France

Groupe hospitalier Cochin-St. Vincent de Paul

🇫🇷

Paris, France

Institut Gustave Roussy (IGR) Centre de Lutte Contre le Canc

🇫🇷

Villejuif Cedex, France

BCCA, Centre for the Southern Interior

🇨🇦

Kelowna, British Columbia, Canada

BC Cancer Agency-Vancouver Island Ctr.

🇨🇦

Victoria, British Columbia, Canada

Weston Park Hospital

🇬🇧

Sheffield, Syorks, United Kingdom

Nevada Cancer Institute

🇺🇸

Las Vegas, Nevada, United States

AZ Cancer Ctr

🇺🇸

Scottsdale, Arizona, United States

Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Alfred Hospital

🇦🇺

Melbourne, Victoria, Australia

BC Cancer Agency-Vancouver

🇨🇦

Vancouver, British Columbia, Canada

McGill University Dept. of Oncology Clinical Research Program

🇨🇦

Montreal, Quebec, Canada

Erasmus MC ae" Daniel den Hoed

🇳🇱

Rotterdam, Netherlands

Univeritaetsklinkum Goettingen

🇩🇪

Gottington, NI, Germany

Universitaetsklinkum Schegwig-Holstein

🇩🇪

Keil, SH, Germany

Universitaesklinkum Leipzig

🇩🇪

Leipzig, Germany

Universitaetsklinkum Mainz

🇩🇪

Mainz, Germany

University of Arkansa for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

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