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Phase II Study of Treatment Selection Based Upon Tumor Thymidylate Synthase Expression in Previously Untreated Patients With Metastatic Colorectal Cancer


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Colorectal Cancer

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Trial Information

Phase II Study of Treatment Selection Based Upon Tumor Thymidylate Synthase Expression in Previously Untreated Patients With Metastatic Colorectal Cancer


OBJECTIVES:

- Compare the response rate (complete and partial), progression-free survival, and
overall survival of patients with previously untreated metastatic or locally recurrent
colorectal adenocarcinoma with high vs low thymidylate synthase (TS) expression treated
with fluorouracil, leucovorin calcium, oxaliplatin, and bevacizumab or irinotecan,
oxaliplatin, and bevacizumab.

- Compare the toxicity of these regimens in these patients.

- Correlate gene expression with response rates in patients treated with these regimens.

- Correlate gene expression with toxicity of these regimens in these patients.

- Correlate dihydropyrimidine dehydrogenase, thymidine phosphorylase, and mammalian
excision repair cross complementary protein expression with antitumor response in
patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
thymidylate synthase (TS) expression levels (high vs low or indeterminate). Patients with
high TS expression are randomized to 1 of 2 treatment arms (arms I or II). Patients with low
or indeterminate TS expression are assigned to arm III.

- Arm I: Patients receive bevacizumab IV over 30-90 minutes followed by oxaliplatin IV
over 2 hours and irinotecan IV over 90 minutes on days 1 and 15.

- Arm II: Patients receive bevacizumab and oxaliplatin as in arm I, leucovorin calcium IV
over 2 hours, and fluorouracil IV over 5 minutes and then continuously over 46 hours on
days 1 and 15.

- Arm III: Patients receive bevacizumab, oxaliplatin, leucovorin calcium, and
fluorouracil as in arm II.

In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease
progression.

Patients are followed up every 3 months for 2 years and then every 6 months for 2 years from
the date of study registration.

PROJECTED ACCRUAL: A total of 117-246 patients (40-72 in arm I, 40-72 in arm II, 37-102 in
arm III) will be accrued for this study within 14-23 months.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of colorectal adenocarcinoma

- Metastatic or locally recurrent disease

- Measurable disease

- At least 2 formalin-fixed paraffin embedded core needle biopsies OR fine needle
aspirate containing a minimum of 3 clusters of malignant cells and fixed tissue from
the previous biopsy

- If no tissue samples are available the patient must be willing to undergo biopsy
of a metastatic site

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

Hepatic

- PT (INR) ≤ 1.5 unless patient is receiving full-dose anticoagulants AND the following
criteria are met:

- In-range INR (usually between 2 and 3) AND on a stable dose of warfarin or low
molecular weight heparin

- No active bleeding or pathological condition that is associated with a high risk
of bleeding

- PTT < 1.5 times upper limit of normal (ULN)

- ALT and AST < 3 times ULN

- Bilirubin ≤ 1.5 times ULN

- No hepatic disease that would preclude study therapy

Renal

- Creatinine ≤ 1.8 mg/dL

- Meets 1 of the following criteria:

- Protein negative on urine dipstick

- Urine protein/creatinine ratio < 1.0

- Less than 2 g protein on 24-hour urine collection

- No renal disease that would preclude study therapy

Cardiovascular

- No arterial thromboembolic events within the past 6 months, including the following:

- Transient ischemic attack

- Cerebrovascular accident

- Unstable angina pectoris

- Myocardial infarction

- Patients with a history of hypertension must meet the following criteria:

- Blood pressure < 150/90 mm Hg

- Stable regimen of anti-hypertensive therapy

- No symptomatic arrhythmia

- No symptomatic congestive heart failure

- No clinically significant peripheral artery disease

- No New York Heart Association class III or IV heart disease

- No other cardiovascular disease that would preclude study therapy

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after study
participation

- Prior non-colorectal malignancies are allowed provided the following criteria are
met:

- No current clinical evidence of persistent or recurrent disease

- No active therapy for non-colorectal malignancy, including hormonal therapy

- No serious nonhealing wound, ulcer, or bone fracture within the past 28 days

- No significant traumatic injury within the past 28 days

- No neuropathy ≥ grade 2

- No other nonmalignant systemic disease that would preclude study therapy

- No ongoing or active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

- No prior chemotherapy for metastatic disease

- Adjuvant therapy completed at least 12 months before first evidence of
metastasis allowed

Endocrine therapy

- Not specified

Radiotherapy

- Not specified

Surgery

- More than 28 days since prior major surgery

- More than 28 days since prior open biopsy

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Response rate (complete response [CR] and partial response [PR]) as measured by RECIST

Safety Issue:

No

Principal Investigator

Neal J. Meropol, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Fox Chase Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000398096

NCT ID:

NCT00098787

Start Date:

July 2005

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • recurrent colon cancer
  • stage IV colon cancer
  • recurrent rectal cancer
  • stage IV rectal cancer
  • adenocarcinoma of the colon
  • adenocarcinoma of the rectum
  • Colorectal Neoplasms

Name

Location

CCOP - Missouri Valley Cancer ConsortiumOmaha, Nebraska  68131
Veterans Affairs Medical Center - Atlanta (Decatur)Decatur, Georgia  30033
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
Aurora Presbyterian HospitalAurora, Colorado  80012
Boulder Community HospitalBoulder, Colorado  80301-9019
Penrose Cancer Center at Penrose HospitalColorado Springs, Colorado  80933
CCOP - Colorado Cancer Research ProgramDenver, Colorado  80224-2522
Porter Adventist HospitalDenver, Colorado  80210
Presbyterian - St. Luke's Medical CenterDenver, Colorado  80218
St. Joseph HospitalDenver, Colorado  80218
Rose Medical CenterDenver, Colorado  80220
Swedish Medical CenterEnglewood, Colorado  80110
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical CenterGrand Junction, Colorado  81502
Sky Ridge Medical CenterLone Tree, Colorado  80124
Hope Cancer Care Center at Longmont United HospitalLongmont, Colorado  80502
St. Mary - Corwin Regional Medical CenterPueblo, Colorado  81004
North Suburban Medical CenterThornton, Colorado  80229
Mercy Medical Center - Sioux CitySioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLPSioux City, Iowa  51101
St. Luke's Regional Medical CenterSioux City, Iowa  51104
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
MeritCare BemidjiBemidji, Minnesota  56601
Fairview Ridges HospitalBurnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy HospitalCoon Rapids, Minnesota  55433
Fairview Southdale HospitalEdina, Minnesota  55435
Mercy and Unity Cancer Center at Unity HospitalFridley, Minnesota  55432
Hutchinson Area Health CareHutchinson, Minnesota  55350
HealthEast Cancer Care at St. John's HospitalMaplewood, Minnesota  55109
Hennepin County Medical Center - MinneapolisMinneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern HospitalMinneapolis, Minnesota  55407
St. Francis Cancer Center at St. Francis Medical CenterShakopee, Minnesota  55379
Park Nicollet Cancer CenterSt. Louis Park, Minnesota  55416
Regions Hospital Cancer Care CenterSt. Paul, Minnesota  55101
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
CCOP - MeritCare HospitalFargo, North Dakota  58122
Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
MetroHealth Cancer Care Center at MetroHealth Medical CenterCleveland, Ohio  44109
St. Rita's Medical CenterLima, Ohio  45801
Natalie Warren Bryant Cancer Center at St. Francis HospitalTulsa, Oklahoma  74136
Sanford Cancer Center at Sanford USD Medical CenterSioux Falls, South Dakota  57117-5039
Avera Cancer InstituteSioux Falls, South Dakota  57105
Memorial Hospital of South BendSouth Bend, Indiana  46601
CCOP - ColumbusColumbus, Ohio  43206
CCOP - Northern Indiana CR ConsortiumSouth Bend, Indiana  46601
Saint Joseph Regional Medical CenterSouth Bend, Indiana  46617
CCOP - Scott and White HospitalTemple, Texas  76508
University of Florida Shands Cancer CenterGainesville, Florida  32610-0232
Winship Cancer Institute of Emory UniversityAtlanta, Georgia  30322
McCreery Cancer Center at Ottumwa RegionalOttumwa, Iowa  52501
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Adena Regional Medical CenterChillicothe, Ohio  54601
Doctors Hospital at Ohio HealthColumbus, Ohio  43228
Riverside Methodist Hospital Cancer CareColumbus, Ohio  43214
Grady Memorial HospitalDelaware, Ohio  43015
Fairfield Medical CenterLancaster, Ohio  43130
Strecker Cancer Center at Marietta Memorial HospitalMarietta, Ohio  45750
Licking Memorial Cancer Care Program at Licking Memorial HospitalNewark, Ohio  43055
Community Hospital of Springfield and Clark CountySpringfield, Ohio  45505
Genesis - Good Samaritan HospitalZanesville, Ohio  43701
Swedish-American Regional Cancer CenterRockford, Illinois  61104-2315
Indiana University Melvin and Bren Simon Cancer CenterIndianapolis, Indiana  46202-5289
Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicago, Illinois  60611
Decatur Memorial Hospital Cancer Care InstituteDecatur, Illinois  62526
Elkhart General HospitalElkhart, Indiana  46515
Howard Community HospitalKokomo, Indiana  46904
Lakeland Regional Cancer Care Center - St. JosephSt. Joseph, Michigan  49085
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital MarltonMarlton, New Jersey  08053
Mount Carmel Health - West HospitalColumbus, Ohio  43222
Morgan Cancer Center at Lehigh Valley Hospital - Cedar CrestAllentown, Pennsylvania  18105
Fox Chase Cancer Center - PhiladelphiaPhiladelphia, Pennsylvania  19111-2497
Hematology Oncology Associates - SkokieSkokie, Illinois  60076
Hematology and Oncology AssociatesChicago, Illinois  60611
North Shore Oncology and Hematology Associates, Limited - LibertyvilleLibertyville, Illinois  60048
Center for Cancer Therapy at LaPorte Hospital and Health ServicesLa Porte, Indiana  46350
Immanuel Medical CenterOmaha, Nebraska  68122
Creighton University Medical CenterOmaha, Nebraska  68131-2197
Bryn Mawr HospitalBryn Mawr, Pennsylvania  19010
Lankenau Cancer Center at Lankenau HospitalWynnewood, Pennsylvania  19096
St. Anthony Central HospitalDenver, Colorado  80204-1335
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
Cancer Resource Center - LincolnLincoln, Nebraska  68510
Saint Joseph HospitalChicago, Illinois  60657
Cancer Care and Hematology Specialists of Chicagoland - NilesNiles, Illinois  60714
William N. Wishard Memorial HospitalIndianapolis, Indiana  46202
Lakeside Cancer Specialists, PLLCSaint Joseph, Michigan  49085
Willmar Cancer Center at Rice Memorial HospitalWillmar, Minnesota  56201
Alegant Health Cancer Center at Bergan Mercy Medical CenterOmaha, Nebraska  68124
Grant Medical Center Cancer CareColumbus, Ohio  43215
Knox Community HospitalMount Vernon, Ohio  43050
McGlinn Family Regional Cancer Center at Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
Veterans Affairs Medical Center - IndianapolisIndianapolis, Indiana  46202
Cancer Center of Paoli Memorial HospitalPaoli, Pennsylvania  19301-1792
CCOP - Main Line HealthWynnewood, Pennsylvania  19096
Provena St. Mary's Regional Cancer Center - KankakeeKankakee, Illinois  60901
Minnesota Oncology - MaplewoodMaplewood, Minnesota  55109
Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdale, Minnesota  55422-2900
Lakeview HospitalStillwater, Minnesota  55082
Minnesota Oncology - WoodburyWoodbury, Minnesota  55125
California Cancer Care, Incorporated - GreenbraeGreenbrae, California  94904
Erlanger Cancer Center at Erlanger Hospital - BaronessChattanooga, Tennessee  37403
Lakeside HospitalOmaha, Nebraska  68130
Littleton Adventist HospitalLittleton, Colorado  80122
Parker Adventist HospitalParker, Colorado  80138
New Ulm Medical CenterNew Ulm, Minnesota  56073
Roger Maris Cancer Center at MeritCare HospitalFargo, North Dakota  58122
Southern Ohio Medical Center Cancer CenterPortsmouth, Ohio  45662