Clinical trial NCT00864253: A Trial of ABI-007 Versus Dacarbazine in Previously Untreated Patients With Metastatic Malignant Melanoma
Official title: An Open-Label, Multicenter, Phase III Trial of ABI-007 vs Dacarbazine in Previously Untreated Patients With Metastatic Malignant Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malignant Melanoma
Keywords: Melanoma
Malignant
Abraxane
ABI-007
Dacarbazine
Dtic-Dome
Lead sponsor: Celgene
Sponsor class: INDUSTRY
Collaborators: name: University of Arizona
First posted: 2009-03-18
Enrollment: 529
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival (PFS) Based on a Blinded Radiology Assessment of Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines
timeFrame: Response assessment completed every 8 weeks until disease progression for up to 106 weeks; data cut off 30 June 2012
Secondary outcomes:
measure: Participant Survival
timeFrame: Up to 38 months; Up to data cut off of 30 June 2012
measure: Summary of Treatment-emergent Adverse Events (AEs)
timeFrame: Maximum exposure to study drug was 106 weeks; up to data cut off of 30 June 2012
measure: Number of Participants Experiencing Dose Reductions, or Dose Interruptions, or Dose Delays of Study Drug
timeFrame: Maximum study drug exposure 106 weeks; data cut off 30 June 2012
measure: Nadir for the Absolute Neutrophil Count (ANC) Measurements
timeFrame: Day 1 up to 106 weeks; up to data cut off 30 June 2012
measure: Nadir for White Blood Cells (WBCs) Measurements
timeFrame: Day 1 up to 106 weeks; up to data cut off 30 June 2012
measure: Nadir for Platelet Count Measurements.
timeFrame: Day 1 up to 106 weeks; up to data cut off 30 June 2012
measure: Nadir for the Hemoglobin Count Measurements
timeFrame: Day 1 up to 106 weeks; up to data cut off 30 June 2012
measure: Pharmacokinetic Parameters
timeFrame: On Cycle 1, Day 1 blood samples were taken at 0.25, 3.5, and 24 hr post-infusion end of the initial dose
Other outcomes:
measure: Progression-free Survival (PFS) Based on Investigator Assessment Using RECIST Response Guidelines
timeFrame: Response assessments completed every 8 weeks until disease progression; up to data cut off 30 June 2012; 38 months
measure: Percent of Participants Who Achieve an Objective Confirmed Complete or Partial Response Based on Blinded Radiology Assessment of Response by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0
timeFrame: every 8 weeks; up to data cut off 30 June 2012
measure: Percent of Participants With Stable Disease (SD) for ≥ 16 Weeks, or Confirmed Complete or Partial Response (i.e., Disease Control) Based on a Blinded Radiology Assessment of Response
timeFrame: Response assessment completed every 8 weeks until disease progression; up to data cut-off 30 June 2012
measure: Duration of Response (DOR) in Responding Participants
timeFrame: up to data cut off 30 June 2012
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: AZ Cancer Ctr
state: Arizona
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Hot Springs
country: United States
facility: Genesis Cancer Ctr - Hot Springs
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansa for Medical Sciences
state: Arkansas
city: Beverly Hills
country: United States
facility: Tower Cancer Research Foundation
state: California
city: Encinitas
country: United States
facility: San Diego Pacific Oncology and Hematology Associates
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California/Norris Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of CA Los Angeles
state: California
city: San Francisco
country: United States
facility: St. Mary's Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Jacksonville
country: United States
facility: Baptist Cancer Institute
state: Florida
city: Lakeland
country: United States
facility: Lakeland Regional Cancer Center
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital and Clincs/SCCC
state: Florida
city: Maryville
country: United States
facility: Waren Billhartz Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Cedar Rapids
country: United States
facility: IA Blood and Cancer Care, PLC
state: Iowa
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Springfield
country: United States
facility: St. John's Medical Research
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Cancer Institute
state: Nevada
city: Morristown
country: United States
facility: Atlantic Melanoma Center
state: New Jersey
city: Winston-Salem
country: United States
facility: Piedmont Hematology
state: North Carolina
city: Columbus
country: United States
facility: OH State University Arthur G. James Cancer Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Cancer Institute of OK
state: Oklahoma
city: Bethlehem
country: United States
facility: St. Luke's Hospital & Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Dallas
country: United States
facility: Mary Crowley Research Center
state: Texas
city: Houston
country: United States
facility: Univ of TX MD Anderson Cancer Ctr
state: Texas
city: Houston
country: United States
facility: Univ of TX Med School at Houston
state: Texas
city: Lubbock
country: United States
facility: Covenant Health System DBA Joe Arrington Cancer Research and Treatment Center
state: Texas
city: Richardson
country: United States
facility: Hope Oncology
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialist
state: Utah
city: Seattle
country: United States
facility: Univ. of Washington Medical Center/Seattle Cancer Care Alliance
state: Washington
city: Spokane
country: United States
facility: Evergreen Hematology & Oncology
state: Washington
city: Port Macquarie
country: Australia
facility: Port Macquarie Base Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Sydney West Cancer Trials Centre/Westmead Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital, Department of Medical Oncology
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Nedlands Perth
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Kelowna
country: Canada
facility: BCCA Centre for the Southern Interior
state: British Columbia
city: Kelowna
country: Canada
facility: BCCA, Centre for the Southern Interior
state: British Columbia
city: Surrey
country: Canada
facility: BC Cancer Agency-Fraser Valley Ctr.
state: British Columbia
city: Vancouver
country: Canada
facility: BC Cancer Agency-Vancouver
state: British Columbia
city: Victoria
country: Canada
facility: BC Cancer Agency-Vancouver Island Ctr.
state: British Columbia
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Missiauga
country: Canada
facility: Credit Valley Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill University Dept. of Oncology Clinical Research Program
state: Quebec
city: Bordeaux
country: France
facility: Hopital Saint Andre' CHU de Bordeaux
city: Grenoble Cedex 09
country: France
facility: Centre Hospitaller Universitaire de Grenoble
city: Lile Cedax
country: France
facility: CHRU Hopital Claude Huriez
city: Limoges cedex
country: France
facility: Hopital Dypuytren-CHU de Limoges
city: Lyon
country: France
facility: Centre Leon Berad
city: Marseille Cedex 9
country: France
facility: Hopital Sainte Marguerite
city: Montepellier Cedex 5
country: France
facility: CHU Hopital Saint Eloi
city: Montpellier
country: France
facility: Centre Regional Val d' Aurelle Paul Lamarque
city: Nice Cedex 3
country: France
facility: Hopital de 1 Archet 2
city: Paris Cedex
country: France
facility: Hopital Saint-Louis
city: Paris
country: France
facility: Hopital Bichat
city: Paris
country: France
facility: Groupe hospitalier Cochin-St. Vincent de Paul
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy (IGR) Centre de Lutte Contre le Canc
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin
state: BE
city: Heidelberg
country: Germany
facility: Universitaetsklinkum Heidelberg
state: BW
city: Heidelber
country: Germany
facility: Universitaetsklinkum Heidelberg
state: BW
city: Tuebingen
country: Germany
facility: Universitaetsklinkum Tuebingen
state: BW
city: Wuerzburg
country: Germany
facility: Universitaetsklinkum Wuerzburg PS
state: BY
city: Hamburg
country: Germany
facility: Universitaetsklinkum Hamburg-Eppendorf
state: HH
city: Gottington
country: Germany
facility: Univeritaetsklinkum Goettingen
state: NI
city: Hannover
country: Germany
facility: Medizinische Hochschuke Hannover
state: NI
city: Bochum
country: Germany
facility: St. Josef-Hospital
state: Northwest
city: Essen
country: Germany
facility: Universitaetsklinkum Essen
state: Northwest
city: Koln
country: Germany
facility: Universitaetklinkum Koeln
state: Northwest
city: Keil
country: Germany
facility: Universitaetsklinkum Schegwig-Holstein
state: SH
city: Dresden
country: Germany
facility: Universitaetsklinkum Dresden
state: SN
city: Jena
country: Germany
facility: UniversitawtsklinKum Jena
state: Strasse 35
city: Leipzig
country: Germany
facility: Universitaesklinkum Leipzig
city: Mainz
country: Germany
facility: Universitaetsklinkum Mainz
city: Bari
country: Italy
facility: Istituto Tumori "Giovanni Paolo II"
state: BA
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei T
state: FC
city: Genova
country: Italy
facility: IST-Istituto Nazionale per la Ricera sul Cancro
state: GE
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: MI
city: Milano
country: Italy
facility: Istituto Nazionale Tumori
state: MI
city: Padova
country: Italy
facility: IOV-Instituto Oncologico IRCCS
state: PD
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Sense
state: SI
city: Napoli
country: Italy
facility: Ist. Naz. per lo studio e la cura dei tumori G. Pascale
city: Pisa
country: Italy
facility: Ospedale S. Chiara
city: Alkmaar
country: Netherlands
facility: Medisch Centrum Alkmaar
city: Amhem
country: Netherlands
facility: Rijnstate ziekenhuis Arnhem
city: Rotterdam
country: Netherlands
facility: Erasmus MC ae" Daniel den Hoed
city: Barcelona
country: Spain
facility: H Clinic i Provincial
city: Barcelona
country: Spain
facility: H CLINIC I Provincial
city: Madrid
country: Spain
facility: H Clinico San Carlos
city: Sabadell
country: Spain
facility: Corporacion Sanitaria Parc Tauli
city: Chelmsford
country: United Kingdom
facility: Broomfield Hospital
state: Essex
city: Cardiff
country: United Kingdom
facility: Velindre Hospital
state: Glam
city: London
country: United Kingdom
facility: St. George's Hospital
state: GT Lon
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
state: Nott
city: Swansea
country: United Kingdom
facility: Singleton Hospital, Sothwest Wales Inst.
state: S Glam
city: Stroke On Kent
country: United Kingdom
facility: Univ Hospital of North Staffordshire
state: Staffs
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
state: Syorks
city: Wolverhampton
country: United Kingdom
facility: Newcross Hospital
state: Wstmid
city: London
country: United Kingdom
facility: Royal Marsden Hospital London
Study officials:
affiliation: University of Arizona
name: Evan Hersh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Celgene Corporation
name: Ileana Elias, MD
role: STUDY_DIRECTOR
References:
citation: Hersh EM, Del Vecchio M, Brown MP, Kefford R, Loquai C, Testori A, Bhatia S, Gutzmer R, Conry R, Haydon A, Robert C, Ernst S, Homsi J, Grob JJ, Kendra K, Agarwala SS, Li M, Clawson A, Brachmann C, Karnoub M, Elias I, Renschler MF, Hauschild A. A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naive patients with metastatic melanoma. Ann Oncol. 2015 Nov;26(11):2267-74. doi: 10.1093/annonc/mdv324. Epub 2015 Sep 26.