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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Malignant Melanoma	Drug: ABI-007; Drug: Dacarbazine	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	529 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	An Open-Label, Multicenter, Phase III Trial of ABI-007 vs Dacarbazine in Previously Untreated Patients With Metastatic Malignant Melanoma
Study Start Date :	April 2009
Actual Primary Completion Date :	June 2012
Actual Study Completion Date :	February 2014

Arms and Interventions

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Arm	Intervention/treatment
Experimental: ABI-007; Treatment 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.	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.; Other Name: Abraxane
Active Comparator: Dacarbazine; Treatment 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.	Drug: 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.; Other Name: Dtic-Dome, DTIC-Dome

Outcome Measures

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Primary Outcome Measures :

1. Progression Free Survival (PFS) Based on a Blinded Radiology Assessment of Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines [ Time Frame: Response 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 :

1. Participant Survival [ Time Frame: Up 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.
2. Summary of Treatment-emergent Adverse Events (AEs) [ Time Frame: 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.

3. Number of Participants Experiencing Dose Reductions, or Dose Interruptions, or Dose Delays of Study Drug [ Time Frame: Maximum 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.
4. Nadir for the Absolute Neutrophil Count (ANC) Measurements [ Time Frame: Day 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.
5. Nadir for White Blood Cells (WBCs) Measurements [ Time Frame: Day 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.
6. Nadir for Platelet Count Measurements. [ Time Frame: 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.
7. Nadir for the Hemoglobin Count Measurements [ Time Frame: Day 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.
8. 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 ]

Other Outcome Measures:

1. Progression-free Survival (PFS) Based on Investigator Assessment Using RECIST Response Guidelines [ Time Frame: Response assessments completed every 8 weeks until disease progression; up to data cut off 30 June 2012; 38 months ]
   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.
2. 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 [ Time Frame: every 8 weeks; up to data cut off 30 June 2012 ]
   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.
3. 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 [ Time Frame: Response assessment completed every 8 weeks until disease progression; up to data cut-off 30 June 2012 ]

   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.

4. Duration of Response (DOR) in Responding Participants [ Time Frame: up to data cut off 30 June 2012 ]
   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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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Locations

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35243
United States, Arizona
AZ Cancer Ctr
Scottsdale, Arizona, United States, 85258
Arizona Cancer Center
Tucson, Arizona, United States, 85724
United States, Arkansas
Genesis Cancer Ctr - Hot Springs
Hot Springs, Arkansas, United States, 71913
University of Arkansa for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Tower Cancer Research Foundation
Beverly Hills, California, United States, 90211
San Diego Pacific Oncology and Hematology Associates
Encinitas, California, United States, 92024
Loma Linda University Cancer Center
Loma Linda, California, United States, 92354
University of Southern California/Norris Cancer Center
Los Angeles, California, United States, 90033
University of CA Los Angeles
Los Angeles, California, United States, 90095
St. Mary's Medical Center
San Francisco, California, United States, 94117
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
United States, Florida
Baptist Cancer Institute
Jacksonville, Florida, United States, 32207
Lakeland Regional Cancer Center
Lakeland, Florida, United States, 33805
University of Miami Hospital and Clincs/SCCC
Miami, Florida, United States, 33136
United States, Illinois
Waren Billhartz Cancer Center
Maryville, Illinois, United States, 62062
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Iowa
IA Blood and Cancer Care, PLC
Cedar Rapids, Iowa, United States, 52402
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Saint Louis University
Saint Louis, Missouri, United States, 63110
St. John's Medical Research
Springfield, Missouri, United States, 65807
United States, Nevada
Nevada Cancer Institute
Las Vegas, Nevada, United States, 89135
United States, New Jersey
Atlantic Melanoma Center
Morristown, New Jersey, United States, 07962
United States, North Carolina
Piedmont Hematology
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
OH State University Arthur G. James Cancer Hospital
Columbus, Ohio, United States, 43210
United States, Oklahoma
Integris Cancer Institute of OK
Oklahoma City, Oklahoma, United States, 73142
United States, Pennsylvania
St. Luke's Hospital & Health Network
Bethlehem, Pennsylvania, United States, 18015
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19131
United States, Texas
Mary Crowley Research Center
Dallas, Texas, United States, 75246
Univ of TX MD Anderson Cancer Ctr
Houston, Texas, United States, 77030
Univ of TX Med School at Houston
Houston, Texas, United States, 77030
Covenant Health System DBA Joe Arrington Cancer Research and Treatment Center
Lubbock, Texas, United States, 79410
Hope Oncology
Richardson, Texas, United States, 75080
United States, Utah
Utah Cancer Specialist
Salt Lake City, Utah, United States, 84106
United States, Washington
Univ. of Washington Medical Center/Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Evergreen Hematology & Oncology
Spokane, Washington, United States, 99218
Australia, New South Wales
Port Macquarie Base Hospital
Port Macquarie, New South Wales, Australia, 2444
Royal North Shore Hospital
Sydney, New South Wales, Australia, 2065
Sydney West Cancer Trials Centre/Westmead Hospital
Westmead, New South Wales, Australia, 2145
Australia, South Australia
Royal Adelaide Hospital, Department of Medical Oncology
Adelaide, South Australia, Australia, 5000
Australia, Tasmania
Royal Hobart Hospital
Hobart, Tasmania, Australia, 7000
Australia, Victoria
Alfred Hospital
Melbourne, Victoria, Australia, 3004
Australia, Western Australia
Sir Charles Gairdner Hospital
Nedlands Perth, Western Australia, Australia
Royal Perth Hospital
Perth, Western Australia, Australia, 6000
Canada, Alberta
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T2N 4N2
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
BCCA Centre for the Southern Interior
Kelowna, British Columbia, Canada, V1Y 5L3
BCCA, Centre for the Southern Interior
Kelowna, British Columbia, Canada, V1Y 5L3
BC Cancer Agency-Fraser Valley Ctr.
Surrey, British Columbia, Canada, V3V 1Z2
BC Cancer Agency-Vancouver
Vancouver, British Columbia, Canada, V5Z4E6
BC Cancer Agency-Vancouver Island Ctr.
Victoria, British Columbia, Canada, V8R 6V5
Canada, Ontario
London Regional Cancer Program
London, Ontario, Canada, N6A 4L6
Credit Valley Hospital
Missiauga, Ontario, Canada, L5M 2N1
The Ottawa Hospital Regional Cancer Centre
Ottawa, Ontario, Canada, K1H 8L6
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
McGill University Dept. of Oncology Clinical Research Program
Montreal, Quebec, Canada, H2W 1S6
France
Hopital Saint Andre' CHU de Bordeaux
Bordeaux, France, 33075
Centre Hospitaller Universitaire de Grenoble
Grenoble Cedex 09, France, 38043
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, 34298
Hopital de 1 Archet 2
Nice Cedex 3, France, 06200
Hopital Saint-Louis
Paris Cedex, France
Hopital Bichat
Paris, France, 75018
Groupe hospitalier Cochin-St. Vincent de Paul
Paris, France
Institut Gustave Roussy (IGR) Centre de Lutte Contre le Canc
Villejuif Cedex, France, 94805
Germany
Charite Universitaetsmedizin Berlin
Berlin, BE, Germany, 10117
Universitaetsklinkum Heidelberg
Heidelberg, BW, Germany
Universitaetsklinkum Heidelberg
Heidelber, BW, Germany
Universitaetsklinkum Tuebingen
Tuebingen, BW, Germany, 72076
Universitaetsklinkum Wuerzburg PS
Wuerzburg, BY, Germany, 97080
Universitaetsklinkum Hamburg-Eppendorf
Hamburg, HH, Germany
Univeritaetsklinkum Goettingen
Gottington, NI, Germany
Medizinische Hochschuke Hannover
Hannover, NI, Germany, 30625
St. Josef-Hospital
Bochum, NW, Germany, 44791
Universitaetsklinkum Essen
Essen, NW, Germany
Universitaetklinkum Koeln
Koln, NW, Germany
Universitaetsklinkum Schegwig-Holstein
Keil, SH, Germany, 24105
Universitaetsklinkum Dresden
Dresden, SN, Germany
UniversitawtsklinKum Jena
Jena, Strasse 35, Germany, 07743
Universitaesklinkum Leipzig
Leipzig, Germany
Universitaetsklinkum Mainz
Mainz, Germany
Italy
Istituto Tumori "Giovanni Paolo II"
Bari, BA, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei T
Meldola, FC, Italy, 47014
IST-Istituto Nazionale per la Ricera sul Cancro
Genova, GE, Italy, 16132
Istituto Europeo di Oncologia
Milano, MI, Italy, 20141
Istituto Nazionale Tumori
Milano, MI, Italy
IOV-Instituto Oncologico IRCCS
Padova, PD, Italy, 35128
Azienda Ospedaliera Universitaria Sense
Siena, SI, Italy, 53100
Ist. Naz. per lo studio e la cura dei tumori G. Pascale
Napoli, Italy, 80131
Ospedale S. Chiara
Pisa, Italy, 56100
Netherlands
Medisch Centrum Alkmaar
Alkmaar, Netherlands, 1815
Rijnstate ziekenhuis Arnhem
Amhem, Netherlands, 6800TA
Erasmus MC ae" Daniel den Hoed
Rotterdam, Netherlands
Spain
H Clinic i Provincial
Barcelona, Spain, 08036
H CLINIC I Provincial
Barcelona, Spain
H Clinico San Carlos
Madrid, Spain
Corporacion Sanitaria Parc Tauli
Sabadell, Spain, 08208
United Kingdom
Broomfield Hospital
Chelmsford, Essex, United Kingdom, CM1 7ET
Velindre Hospital
Cardiff, Glam, United Kingdom, CF14 2TL
St. George's Hospital
London, GT Lon, United Kingdom, SW12 ORE
Nottingham University Hospitals NHS Trust
Nottingham, Nott, United Kingdom, NG5 1PB
Singleton Hospital, Sothwest Wales Inst.
Swansea, S Glam, United Kingdom, SA28QA
Univ Hospital of North Staffordshire
Stroke on Kent, Staffs, United Kingdom, ST4 6QB
Weston Park Hospital
Sheffield, Syorks, United Kingdom, S10 2SJ
Newcross Hospital
Wolverhampton, Wstmid, United Kingdom, SV10 0QP
Royal Marsden Hospital London
London, United Kingdom, SW3 6JJ

Sponsors and Collaborators

Celgene

University of Arizona

Investigators

Principal Investigator:	Evan Hersh, MD	University of Arizona
Study Director:	Ileana Elias, MD	Celgene Corporation

More Information

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Publications:

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.

Responsible Party:	Celgene
ClinicalTrials.gov Identifier:	NCT00864253 History of Changes
Other Study ID Numbers:	CA033
First Posted:	March 18, 2009
Results First Posted:	June 5, 2014
Last Update Posted:	April 26, 2017
Last Verified:	April 2017

Keywords provided by Celgene:

Melanoma; Malignant; Abraxane	ABI-007; Dacarbazine; Dtic-Dome

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Albumin-Bound Paclitaxel; Paclitaxel	Dacarbazine; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Alkylating; Alkylating Agents