A Study of AC Followed by a Combination of Paclitaxel Plus Trastuzumab or Lapatinib or Both Given Before Surgery to Patients With Operable HER2 Positive Invasive Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
National Surgical Adjuvant Breast and Bowel Project (NSABP)
ClinicalTrials.gov Identifier:
NCT00486668
First received: June 13, 2007
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

The primary purpose of this study is to determine whether breast cancer tumors respond (as measured by pathologic complete response: the absence of microscopic evidence of invasive tumor cells in the breast) to combined chemotherapy of AC(doxorubicin and cyclophosphamide) followed by paclitaxel plus trastuzumab or lapatinib or both given before surgery to patients with HER2-positive breast cancer. Trastuzumab will also be given to all patients after surgery. The study will also evaluate the toxic effects of the chemotherapy combination, including effects on the heart, and will determine survival and progression-free survival 5 years after treatment. Also, the study will look at whether there are gene expression profiles in the tumor tissue that can predict pathologic complete response.


Condition Intervention Phase
Invasive Breast Cancer
Drug: doxorubicin
Drug: cyclophosphamide
Drug: paclitaxel
Drug: trastuzumab
Drug: lapatinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase III Trial of Neoadjuvant Therapy for Patients With Palpable and Operable HER2-Positive Breast Cancer Comparing the Combination of Trastuzumab Plus Lapatinib to Trastuzumab and to Lapatinib Administered With Weekly Paclitaxel Following AC Accompanied by Correlative Science Studies to Identify Predictors of Pathologic Complete Response

Resource links provided by NLM:


Further study details as provided by National Surgical Adjuvant Breast and Bowel Project (NSABP):

Primary Outcome Measures:
  • Determination of pathologic complete response (pCR), defined by the absence of microscopic evidence of invasive tumor cells in the post chemotherapy surgical breast specimen. [ Time Frame: surgery following chemotherapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The determination of pCR in the surgical breast and lymph node specimens following chemotherapy. [ Time Frame: surgery following chemotherapy ] [ Designated as safety issue: No ]
  • Clinical tumor measurement as assessed by physical exam of the breast and lymph nodes [ Time Frame: baseline (prior to starting protocol therapy), at the completion of AC (before starting paclitaxel and trastuzumab and/or lapatinib), and at the conclusion of the sequential regimens (prior to surgery). ] [ Designated as safety issue: No ]
  • Determination of cardiac toxicity as measured by the incidence of cardiac events defined as definite or probable cardiac death [ Time Frame: two year cumulative incidence ] [ Designated as safety issue: Yes ]
  • Determination of non-cardiac toxicities as measured by frequencies of adverse events categorized using CTCAE v3.0. [ Time Frame: through 5 years after entry ] [ Designated as safety issue: Yes ]
  • Overall survival as measured by time from randomization until death from any cause. [ Time Frame: through 5 years after entry ] [ Designated as safety issue: No ]
  • Recurrence-free interval as measured by occurrence of inoperable progressive disease, or from time of surgery to occurrence of local, regional, or distant recurrence in patients with operable disease. [ Time Frame: through 5 years after entry ] [ Designated as safety issue: No ]
  • In tumor tissue, a comparison of array comparative genomic hybridization (CGH) data with gene expression profile data to examine coordinated overexpression of amplified genes, especially in HER2 and cMYC loci. [ Time Frame: Tissue sample collected at surgery following chemotherapy ] [ Designated as safety issue: No ]

Enrollment: 529
Study Start Date: July 2007
Estimated Study Completion Date: July 2015
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1: AC then paclitaxel + trastuzumab
AC followed by paclitaxel plus trastuzumab
Drug: doxorubicin
60 mg/m2 IV every 21 days for cycles 1-4
Drug: cyclophosphamide
600 mg/m2 IV every 21 days for cycles 1-4
Drug: paclitaxel
80 mg/m2 IV on days 1, 8, and 15 every 28 days for cycles 5-8
Drug: trastuzumab
First dose: 4 mg/kg IV, subsequent doses: 2 mg/kg IV weekly beginning on day 1 of the first paclitaxel cycle until 1-7 days before surgery
Experimental: Group 2: AC then paclitaxel + lapatinib
AC followed by paclitaxel plus lapatinib
Drug: doxorubicin
60 mg/m2 IV every 21 days for cycles 1-4
Drug: cyclophosphamide
600 mg/m2 IV every 21 days for cycles 1-4
Drug: paclitaxel
80 mg/m2 IV on days 1, 8, and 15 every 28 days for cycles 5-8
Drug: lapatinib
Group 2: 1250 mg PO daily beginning on day 1 of the first paclitaxel cycle until 1 day before surgery. Group 3: 750 mg PO daily beginning on day 1 of the first paclitaxel cycle until 1 day before surgery.
Experimental: Group 3: AC then paclitaxel + trastuzumab + lapatinib
AC followed by paclitaxel plus trastuzumab plus lapatinib
Drug: doxorubicin
60 mg/m2 IV every 21 days for cycles 1-4
Drug: cyclophosphamide
600 mg/m2 IV every 21 days for cycles 1-4
Drug: paclitaxel
80 mg/m2 IV on days 1, 8, and 15 every 28 days for cycles 5-8
Drug: trastuzumab
First dose: 4 mg/kg IV, subsequent doses: 2 mg/kg IV weekly beginning on day 1 of the first paclitaxel cycle until 1-7 days before surgery
Drug: lapatinib
Group 2: 1250 mg PO daily beginning on day 1 of the first paclitaxel cycle until 1 day before surgery. Group 3: 750 mg PO daily beginning on day 1 of the first paclitaxel cycle until 1 day before surgery.

Detailed Description:

Women with breast cancers that overexpress HER2 are at greater risk for disease progression and death than women whose tumors do not overexpress HER2. Trastuzumab, a recombinant humanized monoclonal antibody against the extracellular domain of the HER2 protein blocks downstream signaling of HER2 and substantially improves the efficacy of chemotherapy in women with metastatic and early-stage HER2-positive breast cancers. Because resistance to trastuzumab eventually results in progressive disease in the metastatic setting and contributes to recurrence following adjuvant trastuzumab-based therapy, it is important to develop agents other than trastuzumab that target HER2 signaling through different mechanisms of action. Lapatinib is an oral, small molecule, dual tyrosine kinase inhibitor of HER2 and EGFR. Lapatinib has shown a lack of cross-resistance with trastuzumab in preclinical studies and activity in women with HER2-positive, metastatic breast cancer that has progressed during trastuzumab treatment. Trastuzumab blocks the downstream signaling of HER2 by binding to the extracellular domain of the receptor. Lapatinib binds to the intracellular domains of HER2 and EGFR and prevents activation of downstream signaling pathways. Because of this different mechanism of action, lapatinib may be effective in trastuzumab-resistant disease. The study will also provide important safety information on trastuzumab and lapatinib combinations immediately following anthracycline exposure, and also provide an initial direct comparison of cardiac effects of trastuzumab and lapatinib when incorporated into a standard sequential AC followed by weekly paclitaxel (neo)adjuvant regimen.

Availability of a second agent that can interrupt HER2-signaling pathways through completely different mechanisms than those of trastuzumab offers the potential for further improvement in the management of patients with HER2-overexpressing breast cancer in both the adjuvant and metastatic setting. Co-administration of both trastuzumab and lapatinib with chemotherapy may be important in improving outcomes in subsets of HER2-positive breast cancers. However, use of two inhibitors of the HER2 pathway will increase costs and may increase toxicity, so it will be important to identify the subsets of patients who would benefit from the dual therapy. Inhibition of HER2 with a single agent clearly is sufficient for many patients as evidenced by the results of the trastuzumab trials. Therefore, co-administration to unselected populations of women with HER2-positive breast cancers would not represent an optimal approach. Given the activity of lapatinib, it is likely that it will also be sufficiently active in inhibiting HER2-pathway activation in some patients to allow for its use as the sole inhibitor of the HER2 pathway. Different populations may also derive greater benefit from one of the HER2-blocking agents relative to the other. Identification of potential predictive factors for pathologic complete response to the combination or to either agent administered alone in neoadjuvant trials would provide important information for adjuvant trials designed to definitively address these important issues.

This study will compare 3 combined chemotherapy regimens: AC followed by paclitaxel plus trastuzumab and lapatinib, AC followed by paclitaxel plus lapatinib, and AC followed by paclitaxel plus trastuzumab given before surgery to patients with HER2-positive breast cancer.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Female
  • 18 years or older
  • ECOG performance status of 0 or 1
  • Primary breast tumor palpable and measures greater than or equal to 2.0 cm by physical exam
  • Diagnosis of invasive adenocarcinoma made by core needle biopsy
  • Breast cancer determined to be HER2-positive
  • LVEF assessment by MUGA scan or ECG within 3 months prior to randomization
  • Blood counts must meet the following criteria:

    • ANC greater than or equal to 1200/mm3
    • Platelet count greater than or equal to 100,000/mm3
    • Hemoglobin greater than or equal to 10 g/dL
  • Serum creatinine less than or equal to ULN for the lab
  • Adequate hepatic function by these criteria:

    • Total bilirubin less than or equal to the ULN for the lab unless the patient has a bilirubin elevation greater than ULN to 1.5 x ULN resulting from Gilbert's disease or similar syndrome due to slow conjugation of bilirubin; and
    • Alkaline phosphatase less than or equal to 2.5 x ULN; and
    • AST less than or equal to 1.5 x ULN for the lab.
  • If skeletal pain present or alkaline phosphatase greater than ULN (but less than or equal to 2.5 x ULN), bone scan or PET scan must not demonstrate metastatic disease
  • If AST or alkaline phosphatase greater than ULN , liver imaging (CT, MRI or PET scan) must not demonstrate definitive metastatic disease and the requirements in criterion for hepatic function must be met
  • Able to swallow oral medications

Exclusion criteria:

  • FNA alone to diagnose the primary tumor
  • Excisional biopsy or lumpectomy was performed prior to randomization
  • Surgical axillary staging procedure prior to randomization. Exceptions: 1) FNA or core biopsy of an axillary node for any patient, and 2) although not recommended, a pre-neoadjuvant therapy SN biopsy for patients with clinically negative axillary nodes.
  • Tumors clinically staged as T4
  • Ipsilateral cN2b or cN3 disease (Patients with cN1 or cN2a disease are eligible)
  • Definitive clinical or radiologic evidence of metastatic disease
  • Synchronous bilateral invasive breast cancer
  • Requirement for chronic use of any of the medications or substances specified in the protocol
  • Treatment including RT, chemotherapy, and/or targeted therapy for the currently diagnosed breast cancer prior to randomization
  • Any sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy, etc. (These patients are eligible if therapy is discontinued prior to randomization)
  • Continued therapy with any hormonal agent such as raloxifene, tamoxifen, or other SERM. (Patients are eligible only if these medications are discontinued prior to randomization)
  • Prior history of breast cancer, including DCIS (Patients with a history of LCIS are eligible)
  • Prior therapy with anthracyclines, taxanes, trastuzumab, or lapatinib for any malignancy
  • Other malignancies unless the patient is considered to be disease-free for 5 or more years prior to randomization and is deemed by her physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
  • Cardiac disease that would preclude the use of the drugs included in the B-41 treatment regimens. This includes but is not confined to:

    • Active cardiac disease:

      • angina pectoris requiring the use of anti-anginal medication;
      • ventricular arrhythmias except for benign premature ventricular contractions controlled by medication;
      • conduction abnormality requiring a pacemaker;
      • supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; and
      • clinically significant valvular disease.
    • History of cardiac disease:

      • myocardial infarction;
      • congestive heart failure; or
      • cardiomyopathy.
  • Uncontrolled hypertension, defined as blood pressure greater than 150/90 mm/Hg on antihypertensive therapy
  • History of or current symptomatic interstitial pneumonitis or pulmonary fibrosis or definitive evidence of interstitial pneumonitis or pulmonary fibrosis described on CT or chest x-ray in asymptomatic patients
  • Sensory/motor neuropathy greater than or equal to grade 2, as defined by the NCI's CTCAE v3.0
  • Malabsorption syndrome, ulcerative colitis, resection of the stomach or small bowel, or other disease significantly affecting gastrointestinal function
  • Other non-malignant systemic disease that would preclude treatment with any of the treatment regimens or would prevent required follow-up
  • Conditions that would prohibit administration of corticosteroids
  • Administration of any investigational agents within 30 days before randomization
  • Pregnancy or lactation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00486668

  Hide Study Locations
Locations
United States, Alabama
MBCCOP, Gulf Coast
Mobile, Alabama, United States, 36608
United States, California
Scripps Cancer Center-San Diego
La Jolla, California, United States, 92037
Pacific Shores Medical Group
Long Beach, California, United States, 90813
University of California, Irvine Medical Center
Long Beach, California, United States, 90801
St. Joseph Hospital
Orange, California, United States, 92868
Desert Regional Medical Center Comprehensive Cancer Center
Palm Springs, California, United States, 92262
Stanford University Medical Center
Palo Alto, California, United States, 94304
Sutter Medical Center
Sacramento, California, United States, 95816
Kaiser Permanente-San Diego
San Diego, California, United States, 92120
Santa Rosa Memorial Hospital
Santa Rosa, California, United States, 95403
Kaiser Permanente-Vallejo
Vallejo, California, United States, 94589
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
Memorial Hospital
Colorado Springs, Colorado, United States, 80909
CCOP-Colorado Cancer Research Prog. Inc.(Administrative Only)
Denver, Colorado, United States, 80224
Kaiser Permanente-Franklin
Denver, Colorado, United States, 80205
Kaiser Permanente Rock Creek
Lafayette, Colorado, United States, 80026
United States, Connecticut
Hartford Hospital
Hartford, Connecticut, United States, 06102
Eastern Connecticut Hematology & Oncology Associates
Norwich, Connecticut, United States, 06360
United States, District of Columbia
Sibley Memorial Hospital
Washington, District of Columbia, United States, 20016
United States, Florida
MD Anderson Cancer Center
Orlando, Florida, United States, 32806
United States, Georgia
Phoebe Putney Memorial Hospital
Albany, Georgia, United States, 31701
MBCCOP, Medical College of Georgia Research Institute
Augusta, Georgia, United States, 30912
United States, Hawaii
University of Hawaii
Honolulu, Hawaii, United States, 96813
Kaiser Permanente Hawaii - Moanalua Med Center
Honolulu, Hawaii, United States, 96819
United States, Idaho
Kootenai Cancer Center
Coeur D'Alene, Idaho, United States, 83814
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
Decatur Memorial Hospital
Decatur, Illinois, United States, 62526
Cancer Institute at Alexian Brothers Hospital Network
Elk Grove, Illinois, United States, 60007
Edward Hospital
Naperville, Illinois, United States, 60566
Edward Cancer Center Plainfield
Plainfield, Illinois, United States, 60585
CCOP, Central Illinois
Springfield, Illinois, United States, 62526
CCOP, Carle Cancer Center
Urbana, Illinois, United States, 61801
United States, Indiana
St. Vincent Hospital and Health Care Center
Indianapolis, Indiana, United States, 46260
CCOP, Northern Indiana Cancer Research Consortium
South Bend, Indiana, United States, 46601
United States, Iowa
CCOP, Des Moines, IA
Des Moines, Iowa, United States, 52501
University of Iowa
Iowa City, Iowa, United States, 52242
CCOP, Sioux Community Cancer consortium
Sioux City, Iowa, United States, 51101
United States, Kansas
CCOP, Wichita KS
Wichita, Kansas, United States, 67214
United States, Kentucky
University of Kentucky Medical Center
Lexington, Kentucky, United States, 40536
NortonHealtcare Inc.
Louisville, Kentucky, United States, 40202
United States, Louisiana
CCOP, Ochsner Clinic Foundation
New Orleans, Louisiana, United States, 70121
United States, Maryland
Franklin Square Hospital Center
Baltimore, Maryland, United States, 21237
Greater Baltimore Medical Center
Baltimore, Maryland, United States, 21204
United States, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
United States, Michigan
CCOP, Michigan Cancer Research Consortium
Ann Arbor, Michigan, United States, 48106
Henry Ford Hospital
Detroit, Michigan, United States, 48202
Henry Ford Health System
Detroit, Michigan, United States, 48202
CCOP, Grand Rapids Clnical Oncology Program
Grand Rapids, Michigan, United States, 49503
CCOP, Kalamazoo, MI
Kalamazoo, Michigan, United States, 49007
Michigan State University - Breslin Cancer Center
Lansing, Michigan, United States, 48910
CCOP, William Beaumont Hospital
Royal Oak, Michigan, United States, 48073
Providence Hospital - Southfield
Southfield, Michigan, United States, 48075-9975
United States, Minnesota
Hennepin County Medical Center
Minneapolis, Minnesota, United States, 55415
CCOP, Metro-Minnesota
Minneapolis, Minnesota, United States, 55416
United States, Missouri
University of Missouri-Ellis Fischel
Columbia, Missouri, United States, 65203
CCOP, Kansas City (Administrative Only)
Kansas City, Missouri, United States, 64131
CCOP, Ozark Health Ventures LLC
Springfield, Missouri, United States, 65804
CCOP, Heartland Cancer Research
St. Louis, Missouri, United States, 63131
Saint Louis UniversityHealth Sciences Center
St. Louis, Missouri, United States, 63110
United States, Montana
CCOP, Montana Cancer Consortium
Billings, Montana, United States, 59101
United States, Nebraska
CCOP, Missouri Valley Consortium
Omaha, Nebraska, United States, 74136
United States, New Jersey
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
Newark Beth Israel Medical Center
Newark, New Jersey, United States, 07112
United States, New York
New York Oncology Hematology PC-Albany
Albany, New York, United States, 12206
Cancer Center at Glens Falls Hospital
Glens Falls, New York, United States, 12801
CCOP, Hematology-Oncology Associates of CNY
Syracuse, New York, United States, 13057
United States, North Carolina
Alamance Regional Medical Center
Burlington, North Carolina, United States, 27215
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 28302
CCOP, Southeast Cancer Control Consortium
Charlotte, North Carolina, United States, 28203
Alamance Regional Medical Center - Off site Clinic
Mebane, North Carolina, United States, 27302
Wake Forest University School of Medicine
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Akron City Hospital
Akron, Ohio, United States, 44304
Aultman Hospital
Canton, Ohio, United States, 44710
Case Western Reserve/University Hospitals-Ireland Cancer Cntr.
Cleveland, Ohio, United States, 44106
CCOP, Columbus, OH
Columbus, Ohio, United States, 43215
Ohio State University
Columbus, Ohio, United States, 43017
CCOP, Dayton, OH
Dayton, Ohio, United States, 45429
United States, Oklahoma
CCOP, Oklahoma
Tulsa, Oklahoma, United States, 74136
United States, Pennsylvania
Lehigh Valley Hospital
Allentown, Pennsylvania, United States, 18105
Geisinger Clinic
Danville, Pennsylvania, United States, 17882-2170
Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Albert Einstein Healthcare Network
Philadelphia, Pennsylvania, United States, 19141-3098
NSABP Foundation, Inc.
Pittsburgh, Pennsylvania, United States, 15212
Allegheny General Hospital/Allegheny-Singer Research Institute
Pittsburgh, Pennsylvania, United States, 15212
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States, 15224
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Mercy Hospital
Scranton, Pennsylvania, United States, 18501
Reading Hospital & Medical Center
West Reading, Pennsylvania, United States, 19612
CCOP, Main Line Health
Wynnewood, Pennsylvania, United States, 19096
United States, South Carolina
CCOP, Upstate Carolina
Spartanburg, South Carolina, United States, 29303
United States, South Dakota
Sanford Cancer Center
Souix Falls, South Dakota, United States, 57104
United States, Tennessee
Thompson Cancer Survival Center-Dowell Springs
Knoxville, Tennessee, United States, 37909
United States, Texas
Joe Arrington Cancer Research & Treatment Center
Lubbock, Texas, United States, 79410
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
United States, Virginia
MBCCOP, Virginia Commonwealth University
Richmond, Virginia, United States, 23298
United States, Washington
CCOP, Virginia Mason
Seattle, Washington, United States, 99519
Puget Sound Oncology Consortium
Seattle, Washington, United States, 98109
CCOP, Northwest
Tacoma, Washington, United States, 83706
United States, West Virginia
West Virginia University Hospitals Inc.
Morgantown, West Virginia, United States, 26506-9162
Camden-Clark Memorial Hospital
Parkersburg, West Virginia, United States, 26101
Wheeling Hospital
Wheeling, West Virginia, United States, 26003
United States, Wisconsin
CCOP, Marshfield Clinic
Marshfield, Wisconsin, United States, 54449
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, Ontario
Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Royal Victoria Hospital
Montreal, Quebec, Canada, H3A 1A1
University of Montreal Hospital Group
Montreal, Quebec, Canada
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
St. Mary's Hospital Center
Montreal, Quebec, Canada, H3T 1M5
Centre Hospitalier Affilie Universitaire De Quebec, Hospital du St-Sacrement
Quebec City, Quebec, Canada, G1S 4L8
Puerto Rico
MBCCOP, San Juan, Puerto Rico
San Juan, Puerto Rico, 00936
Sponsors and Collaborators
National Surgical Adjuvant Breast and Bowel Project (NSABP)
GlaxoSmithKline
Investigators
Principal Investigator: Norman Wolmark, MD NSABP Foundation, Inc.
  More Information

Publications:
Responsible Party: National Surgical Adjuvant Breast and Bowel Project (NSABP)
ClinicalTrials.gov Identifier: NCT00486668     History of Changes
Other Study ID Numbers: NSABP B-41
Study First Received: June 13, 2007
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by National Surgical Adjuvant Breast and Bowel Project (NSABP):
HER2 positive breast cancer
invasive breast cancer
lapatinib
neoadjuvant
NSABP
paclitaxel
trastuzumab
doxorubicin
cyclophosphamide

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Liposomal doxorubicin
Trastuzumab
Lapatinib
Doxorubicin
Paclitaxel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on July 31, 2014