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

Malignant Melanoma Clinical Trial

Official title:

An Open-Label, Multicenter, Phase III Trial of ABI-007 vs Dacarbazine in Previously Untreated Patients With Metastatic Malignant Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00864253
• Other study ID #: CA033
• Status: Completed
• Phase: Phase 3
• Start date: April 23, 2009
• Est. completion date: February 12, 2014

Study information

• Verified date: October 2019
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 529
• Est. completion date: February 12, 2014
• Est. primary completion date: June 1, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Malignant Melanoma
• Melanoma

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital, Department of Medical Oncology	Adelaide	South Australia
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands Perth	Western Australia
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Port Macquarie Base Hospital	Port Macquarie	New South Wales
Australia	Royal North Shore Hospital	Sydney	New South Wales
Australia	Sydney West Cancer Trials Centre/Westmead Hospital	Westmead	New South Wales
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	BCCA Centre for the Southern Interior	Kelowna	British Columbia
Canada	BCCA, Centre for the Southern Interior	Kelowna	British Columbia
Canada	London Regional Cancer Program	London	Ontario
Canada	Credit Valley Hospital	Missiauga	Ontario
Canada	McGill University Dept. of Oncology Clinical Research Program	Montreal	Quebec
Canada	The Ottawa Hospital Regional Cancer Centre	Ottawa	Ontario
Canada	BC Cancer Agency-Fraser Valley Ctr.	Surrey	British Columbia
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	BC Cancer Agency-Vancouver	Vancouver	British Columbia
Canada	BC Cancer Agency-Vancouver Island Ctr.	Victoria	British Columbia
France	Hopital Saint Andre' CHU de Bordeaux	Bordeaux
France	Centre Hospitaller Universitaire de Grenoble	Grenoble Cedex 09
France	CHRU Hopital Claude Huriez	Lile Cedax
France	Hopital Dypuytren-CHU de Limoges	Limoges cedex
France	Centre Leon Berad	Lyon
France	Hopital Sainte Marguerite	Marseille Cedex 9
France	CHU Hopital Saint Eloi	Montepellier Cedex 5
France	Centre Regional Val d' Aurelle Paul Lamarque	Montpellier
France	Hopital de 1 Archet 2	Nice Cedex 3
France	Groupe hospitalier Cochin-St. Vincent de Paul	Paris
France	Hopital Bichat	Paris
France	Hopital Saint-Louis	Paris Cedex
France	Institut Gustave Roussy (IGR) Centre de Lutte Contre le Canc	Villejuif Cedex
Germany	Charite Universitaetsmedizin Berlin	Berlin	BE
Germany	St. Josef-Hospital	Bochum	Northwest
Germany	Universitaetsklinkum Dresden	Dresden	SN
Germany	Universitaetsklinkum Essen	Essen	Northwest
Germany	Univeritaetsklinkum Goettingen	Gottington	NI
Germany	Universitaetsklinkum Hamburg-Eppendorf	Hamburg	HH
Germany	Medizinische Hochschuke Hannover	Hannover	NI
Germany	Universitaetsklinkum Heidelberg	Heidelber	BW
Germany	Universitaetsklinkum Heidelberg	Heidelberg	BW
Germany	UniversitawtsklinKum Jena	Jena	Strasse 35
Germany	Universitaetsklinkum Schegwig-Holstein	Keil	SH
Germany	Universitaetklinkum Koeln	Koln	Northwest
Germany	Universitaesklinkum Leipzig	Leipzig
Germany	Universitaetsklinkum Mainz	Mainz
Germany	Universitaetsklinkum Tuebingen	Tuebingen	BW
Germany	Universitaetsklinkum Wuerzburg PS	Wuerzburg	BY
Italy	Istituto Tumori "Giovanni Paolo II"	Bari	BA
Italy	IST-Istituto Nazionale per la Ricera sul Cancro	Genova	GE
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei T	Meldola	FC
Italy	Istituto Europeo di Oncologia	Milano	MI
Italy	Istituto Nazionale Tumori	Milano	MI
Italy	Ist. Naz. per lo studio e la cura dei tumori G. Pascale	Napoli
Italy	IOV-Instituto Oncologico IRCCS	Padova	PD
Italy	Ospedale S. Chiara	Pisa
Italy	Azienda Ospedaliera Universitaria Sense	Siena	SI
Netherlands	Medisch Centrum Alkmaar	Alkmaar
Netherlands	Rijnstate ziekenhuis Arnhem	Amhem
Netherlands	Erasmus MC ae" Daniel den Hoed	Rotterdam
Spain	H Clinic i Provincial	Barcelona
Spain	H CLINIC I Provincial	Barcelona
Spain	H Clinico San Carlos	Madrid
Spain	Corporacion Sanitaria Parc Tauli	Sabadell
United Kingdom	Velindre Hospital	Cardiff	Glam
United Kingdom	Broomfield Hospital	Chelmsford	Essex
United Kingdom	Royal Marsden Hospital London	London
United Kingdom	St. George's Hospital	London	GT Lon
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham	Nott
United Kingdom	Weston Park Hospital	Sheffield	Syorks
United Kingdom	Univ Hospital of North Staffordshire	Stroke On Kent	Staffs
United Kingdom	Singleton Hospital, Sothwest Wales Inst.	Swansea	S Glam
United Kingdom	Newcross Hospital	Wolverhampton	Wstmid
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	St. Luke's Hospital & Health Network	Bethlehem	Pennsylvania
United States	Tower Cancer Research Foundation	Beverly Hills	California
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	IA Blood and Cancer Care, PLC	Cedar Rapids	Iowa
United States	OH State University Arthur G. James Cancer Hospital	Columbus	Ohio
United States	Mary Crowley Research Center	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	San Diego Pacific Oncology and Hematology Associates	Encinitas	California
United States	Genesis Cancer Ctr - Hot Springs	Hot Springs	Arkansas
United States	Univ of TX MD Anderson Cancer Ctr	Houston	Texas
United States	Univ of TX Med School at Houston	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Baptist Cancer Institute	Jacksonville	Florida
United States	Lakeland Regional Cancer Center	Lakeland	Florida
United States	Nevada Cancer Institute	Las Vegas	Nevada
United States	University of Arkansa for Medical Sciences	Little Rock	Arkansas
United States	Loma Linda University Cancer Center	Loma Linda	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	Covenant Health System DBA Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	Waren Billhartz Cancer Center	Maryville	Illinois
United States	University of Miami Hospital and Clincs/SCCC	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Atlantic Melanoma Center	Morristown	New Jersey
United States	Integris Cancer Institute of OK	Oklahoma City	Oklahoma
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Hope Oncology	Richardson	Texas
United States	Saint Louis University	Saint Louis	Missouri
United States	Utah Cancer Specialist	Salt Lake City	Utah
United States	St. Mary's Medical Center	San Francisco	California
United States	AZ Cancer Ctr	Scottsdale	Arizona
United States	Univ. of Washington Medical Center/Seattle Cancer Care Alliance	Seattle	Washington
United States	Evergreen Hematology & Oncology	Spokane	Washington
United States	St. John's Medical Research	Springfield	Missouri
United States	Arizona Cancer Center	Tucson	Arizona
United States	Piedmont Hematology	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Celgene	University of Arizona

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

References & Publications (1)

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-naïve patients with metastatic melanoma. Ann Oncol. 2015 Nov;26(11):2267-74. doi: 10.1093/annonc/mdv324. Epub 2015 Sep 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Progression-free Survival (PFS) Based on Investigator Assessment Using RECIST Response 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, patients 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.	Response assessments completed every 8 weeks until disease progression; up to data cut off 30 June 2012; 38 months
Other	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	RECIST defines complete response (CR): The disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation. All sites must be assessed, including non-measurable sites, such as effusions, or markers. Disappearance of all non-target lesions. The normalization of tumor marker level confirmed at least 4 weeks after initial documentation. Partial response (PR): At least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 4 weeks after initial documentation. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing. As well as persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits.	every 8 weeks; up to data cut off 30 June 2012
Other	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	Disease control is stable disease (SD) for >=16 weeks + complete response (CR) + partial response (PR). See Outcome #4 for definitions of CR and PR.; RECIST defines SD for target lesions as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, no occurrence of progression disease for non-target lesions, and no new lesions.	Response assessment completed every 8 weeks until disease progression; up to data cut-off 30 June 2012
Other	Duration of Response (DOR) in Responding Participants	Duration of response (DOR) as measured by PFS based on radiological review for participants who achieved an objective confirmed response of CR or PR. DOR was defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or participants death from any cause, whichever occurred first. Participants that did not have progression or had not died were censored at the last known time the participant was progression free. Participants that had initiated other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Complete response (CR) and partial response (PR) are defined in outcome #4. Progressive disease was defined as at least a 20% increase in the sum of the longest diameters of target lesions; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.	up to data cut off 30 June 2012
Primary	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.	Response assessment completed every 8 weeks until disease progression for up to 106 weeks; data cut off 30 June 2012
Secondary	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.	Up to 38 months; Up to data cut off of 30 June 2012
Secondary	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.	Maximum exposure to study drug was 106 weeks; up to data cut off of 30 June 2012
Secondary	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.	Maximum study drug exposure 106 weeks; data cut off 30 June 2012
Secondary	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.	Day 1 up to 106 weeks; up to data cut off 30 June 2012
Secondary	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.	Day 1 up to 106 weeks; up to data cut off 30 June 2012
Secondary	Nadir for Platelet Count Measurements.	Maximal degree of myelosuppression was represented by the nadir in platelet count measurements over all treatment cycles.	Day 1 up to 106 weeks; up to data cut off 30 June 2012
Secondary	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.	Day 1 up to 106 weeks; up to data cut off 30 June 2012
Secondary	Pharmacokinetic Parameters		On Cycle 1, Day 1 blood samples were taken at 0.25, 3.5, and 24 hr post-infusion end of the initial dose