Irinotecan, Oxaliplatin, and Capecitabine as First-Line Therapy in Treating Patients With Metastatic or Unresectable Locally Advanced Small Bowel Cancer

Small Intestine Adenocarcinoma Clinical Trial

Official title:

A Phase II Trial of Pharmacogenetic-Based Dosing of Irinotecan, Oxaliplatin, and Capecitabine as First-Line Therapy for Advanced Small Bowel Adenocarcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00433550
• Other study ID #: NCCTG-N0543
• Secondary ID: NCI-2009-00650CD
• Status: Active, not recruiting
• Phase: Phase 2
• First received: February 8, 2007
• Last updated: August 12, 2016
• Start date: May 2007

Study information

• Verified date: August 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well giving irinotecan hydrochloride together with oxaliplatin and capecitabine works as first-line therapy in treating patients with metastatic or unresectable locally advanced small bowel cancer. Drugs used in chemotherapy, such as irinotecan hydrochloride, oxaliplatin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

Description:

PRIMARY OBJECTIVE:

To assess the confirmed tumor response of the combination of oxaliplatin, irinotecan (irinotecan hydrochloride), and capecitabine in patients with advanced adenocarcinoma of the small bowel when dosed according to UGT1A1 genotype.

SECONDARY OBJECTIVES:

1. To assess the toxicity of this regimen in these groups of patients.

2. To gain preliminary data on whether microsatellite instability influences outcome within this arm.

3. To gain preliminary data on whether evidence of celiac disease may affect toxicity and outcome.

4. To gain preliminary data on whether site of tumor origin (duodenal, jejunal, or ileal) affects response or survival.

OUTLINE: Patients are assigned to 1 of 3 treatment groups based on UGT1A1 genotype.

GROUP 1 (6/6 UGT1A1 genotype): Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes and oxaliplatin IV over 2 hours on day 1 and capecitabine orally (PO) twice daily (BID) on days 2-15.

GROUP 2 (6/7 UGT1A1 genotype): Patients receive irinotecan hydrochloride as in group 1. They also receive oxaliplatin and capecitabine as in group 1 but at lower doses.

GROUP 3 (7/7 UGT1A1 genotype): Patients receive irinotecan hydrochloride, oxaliplatin, and capecitabine as in group 1 but at lower doses.

In all groups, treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

After the completion of study treatment, patients are followed every 6 weeks for 2 years and then periodically thereafter.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 33
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Confirmation UDP glucuronosyltransferase 1 family, polypeptide A complex locus (UGT1A1) TA indel genotype of 6/6, 6/7, or 7/7 after pre-registration but prior to registration

• Patient willingness to provide a serum sample for analysis for celiac disease (tissue transglutaminase antibodies)

• Small bowel adenocarcinoma, either metastatic or locally advanced and not surgically resectable; NOTE: periampullary carcinoma and appendiceal cancer are not eligible

• Histologic or cytologic confirmation of adenocarcinoma consistent with small bowel origin; biopsy can be of primary tumor or can be from a metastatic site if there is a primary small bowel tumor currently or previously present

• Measurable disease; for patients with lesions >= 1 cm but < 2 cm, spiral computed tomography (CT) scan imaging must be used for tumor assessments

• Life expectancy >= 12 weeks

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

• >= 4 weeks since prior major surgery to time of registration

• >= 2 weeks from completion of any radiation treatment

• Absolute neutrophil count (ANC) >= 1,500/mm^3

• Platelets >= 100,000/mm^3

• Serum glutamic oxaloacetic transaminase (SGOT) =< 5 x upper normal limit (UNL); =< 2.5 x UNL if no liver metastases

• Total bilirubin:

• For 6/6 patients: =< upper limit of normal (ULN)

• For 6/7 or 7/7 patients: =< 2.0 x ULN

• Hemoglobin >= 9.0 g/dL

• Creatinine =< 1.5 x UNL (if > 1.5 x UNL, calculated creatinine clearance should be checked.; if it is > 60 mL/min, then the patient is eligible for the study)

• Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only

Exclusion Criteria

• Prior chemotherapy regimen for advanced small bowel cancer (prior adjuvant chemotherapy with fluorouracil (5FU)/leucovorin is permitted if last dose was administered >= 3 months prior to registration); prior oxaliplatin or irinotecan use as adjuvant therapy is not permitted

• Prior radiotherapy to > 25% of bone marrow

• Active or uncontrolled infection

• Evidence of serious intercurrent illness (e.g., unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia)

• Pregnant women; women of child-bearing potential and men must agree to use adequate contraception (diaphragm, birth control pills, injections, foams, intrauterine device [IUD], or abstinence, etc.) for the duration of study participation; if a woman becomes pregnant or suspects that she is pregnant while participating in this study, she should inform her treating physician immediately and all study treatment discontinued

• Nursing women; breast-feeding should be discontinued when the mother is treated with these agents

• Men or women of childbearing potential who are unwilling to employ adequate contraception

• Current evidence of other malignancy besides small bowel adenocarcinoma, with exception of non-melanoma skin cancer

• Known central nervous system metastases or carcinomatous meningitis

• Preexisting sensory neuropathy >= grade 2 from any cause interfering with function

• Concurrent therapy with sorivudine, brivudine, lamivudine, or stavudine

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Intestinal Neoplasms
• Recurrent Small Intestine Cancer
• Small Intestine Adenocarcinoma

Intervention

Drug:
• capecitabine
given orally
• irinotecan hydrochloride
given IV
• oxaliplatin
given IV

Locations

Country	Name	City	State
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota
United States	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	St. Joseph's Medical Center	Brainerd	Minnesota
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	CCOP - Duluth	Duluth	Minnesota
United States	Essentia Health - Duluth Clinic	Duluth	Minnesota
United States	Miller - Dwan Medical Center	Duluth	Minnesota
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Community Cancer Center	Elyria	Ohio
United States	Hematology Oncology Center	Elyria	Ohio
United States	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	St. Peter's Hospital	Helena	Montana
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Dickinson County Healthcare System	Iron Mountain	Michigan
United States	Foote Memorial Hospital	Jackson	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas
United States	Lima Memorial Hospital	Lima	Ohio
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology - Maplewood	Maplewood	Minnesota
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	St. Nicholas Hospital	Sheboygan	Wisconsin
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Regions Hospital Cancer Care Center	St. Paul	Minnesota
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Anne Mercy Hospital	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	St. John Macomb Hospital	Warren	Michigan
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Minnesota Oncology - Woodbury	Woodbury	Minnesota

Sponsors (4)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI), Pfizer, Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed tumor response		36 weeks	No
Secondary	Overall survival		Up to 2 years	No
Secondary	Time to disease progression		Up to 2 years	No
Secondary	Duration of response		Up to 2 years	No
Secondary	Time to treatment failure		Up to 2 years	No