Irinotecan and Docetaxel in Treating Patients With Refractory Metastatic Breast Cancer

Phase II Trial of Weekly Irinotecan and Docetaxel in Refractory Metastatic Breast Cancer

RATIONALE: Drugs used in chemotherapy, such as irinotecan and docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving irinotecan together with docetaxel works in treating patients with refractory metastatic breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: docetaxel; Drug: irinotecan hydrochloride

Detailed Description

OBJECTIVES:

Primary

• Determine the antitumor activity of irinotecan and docetaxel, in terms of response rate, in patients with refractory metastatic breast cancer.

Secondary

• Determine the toxicity profile of this regimen in these patients.
• Determine the progression-free and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive docetaxel IV over 1 hour followed by irinotecan IV over 1 hour on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) receive 2 additional courses beyond CR.

Patients are followed every 2 months until disease progression and then every 6 months thereafter.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic Scottsdale
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
  • Illinois
    • Aurora, Illinois, United States, 60507
      • Rush-Copley Cancer Care Center
    • Bloomington, Illinois, United States, 61701
      • St. Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Graham Hospital
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Eureka, Illinois, United States, 61530
      • Eureka Community Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Cottage Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Clinic
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Hopedale, Illinois, United States, 61747
      • Hopedale Medical Complex
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates, Limited - West
    • Kewanee, Illinois, United States, 61443
      • Kewanee Hospital
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Normal, Illinois, United States, 61761
      • Community Cancer Center
    • Ottawa, Illinois, United States, 61350
      • Community Hospital of Ottawa
    • Ottawa, Illinois, United States, 61350
      • Oncology Hematology Associates of Central Illinois, PC - Ottawa
    • Pekin, Illinois, United States, 61554
      • Cancer Treatment Center at Pekin Hospital
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peoria, Illinois, United States, 61637
      • OSF St. Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • CCOP - Illinois Oncology Research Association
    • Peoria, Illinois, United States, 61615
      • Oncology Hematology Associates of Central Illinois, PC - Peoria
    • Peru, Illinois, United States, 61354
      • Illinois Valley Community Hospital
    • Spring Valley, Illinois, United States, 61362
      • St. Margaret's Hospital
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center at Carle Foundation Hospital
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • St. Francis Hospital and Health Centers - Beech Grove Campus
    • Michigan City, Indiana, United States, 46360
      • Saint Anthony Memorial Health Centers
    • Richmond, Indiana, United States, 47374
      • Reid Hospital & Health Care Services, Incorporated
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic, PC
    • Cedar Rapids, Iowa, United States, 52402
      • St. Luke's Hospital
    • Cedar Rapids, Iowa, United States, 52403
      • Cedar Rapids Oncology Associates
    • Cedar Rapids, Iowa, United States, 52403
      • Mercy Regional Cancer Center at Mercy Medical Center
    • Des Moines, Iowa, United States, 50309
      • CCOP - Iowa Oncology Research Association
    • Des Moines, Iowa, United States, 50309
      • John Stoddard Cancer Center at Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates at John Stoddard Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates at Mercy Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Cancer Center at Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50307
      • Mercy Capitol Hospital
    • Des Moines, Iowa, United States, 50316-2301
      • John Stoddard Cancer Center at Iowa Lutheran Hospital
    • Ottumwa, Iowa, United States, 52501
      • Ottumwa Regional Health Center Cancer Center
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates, LLP
    • Sioux City, Iowa, United States, 51104
      • St. Luke's Regional Medical Center
    • Sioux City, Iowa, United States, 51104
      • Mercy Medical Center - Sioux City
    • West Des Moines, Iowa, United States, 50266
      • Medical Oncology and Hematology Associates - West Des Moines
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas, PA - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas, PA - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - El Dorado
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas, PA - Kingman
    • Liberal, Kansas, United States, 67901
      • Southwest Medical Center
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas, PA - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas, PA - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas, PA - Pratt
    • Salina, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas, PA - Wellington
    • Wichita, Kansas, United States, 67203
      • Associates in Womens Health, PA - North Review
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas, PA - Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas, PA - Wichita
    • Wichita, Kansas, United States, 67214
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214
      • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas, PA - Winfield
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center at Bixby Medical Center
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Ann Arbor, Michigan, United States, 48106-0995
      • St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital
    • Dearborn, Michigan, United States, 48123-2500
      • Oakwood Cancer Center at Oakwood Hospital and Medical Center
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Jackson, Michigan, United States, 49201
      • Foote Hospital
    • Lambertville, Michigan, United States, 48144
      • Haematology-Oncology Associates of Ohio and Michigan, PC
    • Lansing, Michigan, United States, 48909
      • Sparrow Regional Cancer Center
    • Monroe, Michigan, United States, 48162
      • Community Cancer Center of Monroe
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital System
    • Saginaw, Michigan, United States, 48601
      • Seton Cancer Institute - Saginaw
    • Warren, Michigan, United States, 48093
      • St. John Macomb Hospital
  • Minnesota
    • Alexandria, Minnesota, United States, 56308
    • Bemidji, Minnesota, United States, 56601
      • MeritCare Clinic - Bemidji
    • Brainerd, Minnesota, United States, 56401
      • Brainerd Medical Center
    • Brainerd, Minnesota, United States, 56401
      • St. Joseph's Medical Center
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy and Unity Cancer Center at Mercy Hospital
    • Duluth, Minnesota, United States, 55805
      • CCOP - Duluth
    • Duluth, Minnesota, United States, 55805
      • St. Mary's - Duluth Clinic Cancer Center
    • Duluth, Minnesota, United States, 55805
      • Miller-Dwan Medical Center
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fergus Falls, Minnesota, United States, 56537
    • Fridley, Minnesota, United States, 55432
      • Mercy and Unity Cancer Center at Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Lichfield, Minnesota, United States, 55355
      • Meeker County Memorial Hospital
    • Mankato, Minnesota, United States, 56002
      • Immanuel St. Joseph's Clinic
    • Maplewood, Minnesota, United States, 55109
      • HealthEast Cancer Care at St. John's Hospital
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology, PA at Maplewood Cancer Center
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center - Minneapolis
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute at Abbott-Northwestern Hospital
    • Montevideo, Minnesota, United States, 56265
      • Chippewa County - Montevideo Hospital
    • Robbinsdale, Minnesota, United States, 55422-2900
      • Hubert H. Humphrey Cancer Center at North Memorial Medical Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • Saint Cloud, Minnesota, United States, 56303
      • Coborn Cancer Center
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
    • Sartell, Minnesota, United States, 56377
      • Adult and Pediatric Urology, P.L.L.P.
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Cancer Center
    • St Paul, Minnesota, United States, 55102
      • St. Joseph's Hospital
    • St. Cloud, Minnesota, United States, 56303
      • CentraCare Clinic - River Campus
    • St. Louis Park, Minnesota, United States, 55416
      • Park Nicollet Health Services
    • St. Paul, Minnesota, United States, 55102
      • United Hospital
    • St. Paul, Minnesota, United States, 55101
      • Regions Hospital Cancer Care Center
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Woodbury, Minnesota, United States, 55125
      • Woodwinds Health Campus
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology, PA - Woodbury
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Cancer Resource Center - Lincoln
    • Omaha, Nebraska, United States, 68106
      • CCOP - Missouri Valley Cancer Consortium
    • Omaha, Nebraska, United States, 68122
      • Immanuel Medical Center
    • Omaha, Nebraska, United States, 68124
      • Alegant Health Cancer Center at Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68131-2197
      • Creighton University Medical Center
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Bismarck Cancer Center
    • Bismarck, North Dakota, United States, 58501
      • Cancer Care Center at Medcenter One Hospital
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic, P. C.
    • Bismarck, North Dakota, United States, 58502
      • St. Alexius Medical Center
    • Fargo, North Dakota, United States, 58122
      • CCOP - MeritCare Hospital
    • Fargo, North Dakota, United States, 58122
      • MeritCare Medical Group
  • Ohio
    • Bowling Green, Ohio, United States, 43402
      • Wood County Oncology Center
    • Dayton, Ohio, United States, 45428
      • Veterans Affairs Medical Center - Dayton
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital
    • Dayton, Ohio, United States, 45409
      • David L. Rike Cancer Center at Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Cancer Care Center
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Medical Associates
    • Fremont, Ohio, United States, 43420
      • Fremont Memorial Hospital
    • Kenton, Ohio, United States, 43326
      • Kenton Oncology, Incorporated
    • Kettering, Ohio, United States, 45429
      • Charles F. Kettering Memorial Hospital
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Maumee, Ohio, United States, 43537
      • Northwest Ohio Oncology Center
    • Maumee, Ohio, United States, 43537
      • St. Luke's Hospital
    • Middletown, Ohio, United States, 45044
      • Middletown Regional Hospital
    • Oregon, Ohio, United States, 43616
      • St. Charles Mercy Hospital
    • Oregon, Ohio, United States, 43616
      • Toledo Clinic - Oregon
    • Sandusky, Ohio, United States, 44870
      • Firelands Regional Medical Center
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care, Incorporated
    • Sylvania, Ohio, United States, 43560
      • Flower Hospital Cancer Center
    • Tiffin, Ohio, United States, 44883
      • Mercy Hospital of Tiffin
    • Toledo, Ohio, United States, 43608
      • St. Vincent Mercy Medical Center
    • Toledo, Ohio, United States, 43606
      • Toledo Hospital
    • Toledo, Ohio, United States, 43614
      • Medical University of Ohio Cancer Center
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic, Incorporated - Main Clinic
    • Toledo, Ohio, United States, 43623
      • CCOP - Toledo Community Hospital
    • Troy, Ohio, United States, 45373-1300
      • UVMC Cancer Care Center at Upper Valley Medical Center
    • Wauseon, Ohio, United States, 43567
      • Fulton County Health Center
    • Wright-Patterson Afb, Ohio, United States, 45433-5529
      • United States Air Force Medical Center - Wright-Patterson
    • Xenia, Ohio, United States, 45385
      • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at St. Francis Hospital
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822-0001
      • Geisinger Medical Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Cancer Center at Allegheny General Hospital
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group - Scenery Park
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sioux Valley Hospital and University of South Dakota Medical Center
    • Sioux Falls, South Dakota, United States, 57105
      • Medical X-Ray Center, PC
  • Wisconsin
    • Fond du Lac, Wisconsin, United States, 54935
      • Central Wisconsin Cancer Program at Agnesian HealthCare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the breast

  • Metastatic disease
• Previously treated with chemotherapy in the adjuvant setting and/or for metastatic disease

• At least one unidimensionally measurable lesion

  • At least 20 mm by CT scan or MRI OR at least 10 mm by spiral CT scan
  • Superficial clinical lesions (e.g., skin nodules or palpable lymph nodes) are allowed
  • Lesions on chest x-ray are allowed provided they are clearly defined and surrounded by aerated lung

  • The following are not considered measurable:

    • Bone lesions
    • Ascites
    • Leptomeningeal disease
    • Pleural/pericardial effusion
    • Inflammatory breast disease
    • Lymphangitis cutis/pulmonis
    • Cystic lesions
• No known CNS metastases unless controlled by prior surgery and/or radiotherapy

• Hormone receptor status:

  • Estrogen receptor (ER) and/or progesterone receptor (PR) status known

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Granulocyte count ≥ 1,500/mm^3
• Hemoglobin ≥ 8.0 g/dL
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ upper limit of normal (ULN)

• Meets 1 of the following criteria:

  • AST or ALT ≤ ULN AND alkaline phosphatase ≤ 5 times ULN
  • Alkaline phosphatase ≤ ULN AND AST or ALT ≤ 5 times ULN
  • AST or ALT ≤ 1.5 times ULN AND alkaline phosphatase ≤ 2.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No myocardial infarction within the past 180 days
• No congestive heart failure
• No unstable angina
• No clinically significant pericardial effusion or arrhythmias

Other

• No active, unresolved infection
• No prior severe hypersensitivity reaction to docetaxel, irinotecan, or any drug formulated with polysorbate 80
• No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No grade 1 or greater sensory or motor neuropathy
• No other concurrent severe condition that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior trastuzumab (Herceptin®) required for HER-2-positive patients (unless contraindicated)

Chemotherapy

• See Disease Characteristics
• More than 14 days since prior chemotherapy
• No more than 2 prior chemotherapy regimens for metastatic disease

• No prior irinotecan or docetaxel for metastatic disease

  • Docetaxel as adjuvant therapy allowed
• No other concurrent chemotherapy

Endocrine therapy

• Prior hormonal therapy required for patients with ER- and/or PR-positive tumors (unless contraindicated)

Radiotherapy

• See Disease Characteristics
• At least 30 days since prior radiotherapy
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• At least 3 weeks since prior major surgery and recovered

Other

• More than 7 days since prior parenteral antibiotic therapy
• No other concurrent experimental drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: docetaxel + irinotecan; Patients receive docetaxel IV over 1 hour followed by irinotecan IV over 1 hour on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) receive 2 additional courses beyond CR. Patients are followed every 2 months until disease progression and then every 6 months thereafter.

Drug: docetaxel; Drug: irinotecan hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Confirmed tumor response as measured by RECIST criteria	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	Up to 5 years
Distribution of progression times	Up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Tan WW, Hillman DW, Salim M, Northfelt DW, Anderson DM, Stella PJ, Niedringhaus R, Bernath AM, Gamini SS, Palmieri F, Perez EA. N0332 phase 2 trial of weekly irinotecan hydrochloride and docetaxel in refractory metastatic breast cancer: a North Central Cancer Treatment Group (NCCTG) Trial. Ann Oncol. 2010 Mar;21(3):493-497. doi: 10.1093/annonc/mdp328. Epub 2009 Jul 22. Erratum In: Ann Oncol. 2018 Oct 1;29(10):2150.
• Tan WW, Hillman D, Salim M, et al.: N0332 phase II trial of weekly irinotecan and docetaxel in refractory metastatic breast cancer: a North Central Cancer Treatment Group trial. [Abstract] Breast Cancer Res Treat 106 (1): A-1087, S71-2, 2007.

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: March 8, 2004
• First Submitted That Met QC Criteria: March 8, 2004
• First Posted (Estimate): March 9, 2004

Study Record Updates

• Last Update Posted (Estimate): December 13, 2016
• Last Update Submitted That Met QC Criteria: December 9, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer; male breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Docetaxel; Irinotecan
• Other Study ID Numbers: NCCTG-N0332; NCI-2012-02579 (Registry Identifier: CTRP (Clinical Trials Reporting System)); CDR0000354417 (Registry Identifier: PDQ (Physician Data Query))