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

Phase 2

Completed

• Conditions: Recurrent Small Intestine Cancer; Small Intestine Adenocarcinoma
• Interventions: Drug: capecitabine; Drug: irinotecan hydrochloride; Drug: oxaliplatin

• Registration Number: NCT00433550
• Lead Sponsor: Alliance for Clinical Trials in Oncology

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2007-02-08
• Study First Submitted QC: 2007-02-08
• Study First Posted: 2007-02-12
• Study Start: 2007-05
• Primary Completion: 2014-12
• Study Completion: 2016-05
• Results First Submitted: 2017-02-15
• Status Verified: 2017-07
• Results First Submitted QC: 2017-07-25
• Last Update Submitted: 2017-07-25
• Results First Posted: 2017-08-24
• Last Update Posted: 2017-08-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1 (6/6 UGT1A1 genotype)	capecitabine	Patients receive irinotecan hydrochloride IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and capecitabine PO BID on days 2-15
Group 2 (6/7 UGT1A1 genotype)	irinotecan hydrochloride	Patients receive irinotecan hydrochloride as in group 1. They also receive oxaliplatin and capecitabine as in group 1 but at lower doses.
Group 2 (6/7 UGT1A1 genotype)	oxaliplatin	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)	capecitabine	Patients receive irinotecan hydrochloride, oxaliplatin, and capecitabine as in group 1 but at lower doses.
Group 3 (7/7 UGT1A1 genotype)	irinotecan hydrochloride	Patients receive irinotecan hydrochloride, oxaliplatin, and capecitabine as in group 1 but at lower doses.
Group 1 (6/6 UGT1A1 genotype)	oxaliplatin	Patients receive irinotecan hydrochloride IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and capecitabine PO BID on days 2-15
Group 3 (7/7 UGT1A1 genotype)	oxaliplatin	Patients receive irinotecan hydrochloride, oxaliplatin, and capecitabine as in group 1 but at lower doses.
Group 1 (6/6 UGT1A1 genotype)	irinotecan hydrochloride	Patients receive irinotecan hydrochloride IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and capecitabine PO BID on days 2-15
Group 2 (6/7 UGT1A1 genotype)	capecitabine	Patients receive irinotecan hydrochloride as in group 1. They also receive oxaliplatin and capecitabine as in group 1 but at lower doses.

Primary Outcome Measures

Name	Time	Method
Confirmed Tumor Response Rate (Proportion of Participants With Complete Response)	36 weeks	Evaluated using RECIST version 1.0. Confirmed tumor response rate was defined as achieving partial response (PR) or complete response (CR) in two consecutive assessments at least 6 weeks apart. CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. The confirmed response rate is reported as the number of participants with confirmed responses divided by the number of evaluated participants.

Secondary Outcome Measures

Name	Time	Method
Time to Treatment Failure	Up to 2 years	Time to treatment failure is defined to be the time from the date of registration to the date at which the patient is removed from treatment due to progression, toxicity, or refusal. If the patient is considered to have had a major treatment violation or is taken off study as a non-protocol failure, the patient will be censored on the date they are removed from treatment. Time to treatment failure will be analyzed using Kaplan-Meier methods.
Overall Survival	Up to 2 years	Overall survival will be defined as the time from registration to death. Patients lost to follow-up for this endpoint will be censored at the date of last contact (i.e., last known alive). The distribution of overall survival will be estimated using Kaplan-Meier methodology.
Progression Free Survival	Up to 2 years	Time to disease progression is defined as the time from registration to the earlier of documentation of disease progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The distribution of time to progression will be estimated using Kaplan-Meier methodology.
Duration of Response	Up to 2 years	Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented. Duration of response will be analyzed using Kaplan-Meier methods.

Trial Locations

Locations (115)

Medcenter One Hospital Cancer Care Center; 🇺🇸 Bismarck, North Dakota, United States

Regions Hospital Cancer Care Center; 🇺🇸 Saint Paul, Minnesota, United States

Toledo Hospital; 🇺🇸 Toledo, Ohio, United States

Ridgeview Medical Center; 🇺🇸 Waconia, Minnesota, United States

Willmar Cancer Center at Rice Memorial Hospital; 🇺🇸 Willmar, Minnesota, United States

St. Anne Mercy Hospital; 🇺🇸 Toledo, Ohio, United States

St. Vincent Healthcare Cancer Care Services; 🇺🇸 Billings, Montana, United States

Toledo Clinic, Incorporated - Main Clinic; 🇺🇸 Toledo, Ohio, United States

Altru Cancer Center at Altru Hospital; 🇺🇸 Grand Forks, North Dakota, United States

United Hospital; 🇺🇸 Saint Paul, Minnesota, United States

St. Francis Cancer Center at St. Francis Medical Center; 🇺🇸 Shakopee, Minnesota, United States

Northwest Ohio Oncology Center; 🇺🇸 Maumee, Ohio, United States

Lima Memorial Hospital; 🇺🇸 Lima, Ohio, United States

Minnesota Oncology - Woodbury; 🇺🇸 Woodbury, Minnesota, United States

St. James Healthcare Cancer Care; 🇺🇸 Butte, Montana, United States

Medical University of Ohio Cancer Center; 🇺🇸 Toledo, Ohio, United States

Hematology Oncology Center; 🇺🇸 Elyria, Ohio, United States

Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center; 🇺🇸 Green Bay, Wisconsin, United States

St. Alexius Medical Center Cancer Center; 🇺🇸 Bismarck, North Dakota, United States

Lakeview Hospital; 🇺🇸 Stillwater, Minnesota, United States

CCOP - Montana Cancer Consortium; 🇺🇸 Billings, Montana, United States

Billings Clinic - Downtown; 🇺🇸 Billings, Montana, United States

Wood County Oncology Center; 🇺🇸 Bowling Green, Ohio, United States

Toledo Clinic - Oregon; 🇺🇸 Oregon, Ohio, United States

Mercy Hospital of Tiffin; 🇺🇸 Tiffin, Ohio, United States

Green Bay Oncology, Limited - Oconto Falls; 🇺🇸 Oconto Falls, Wisconsin, United States

St. Vincent Hospital Regional Cancer Center; 🇺🇸 Green Bay, Wisconsin, United States

Green Bay Oncology, Limited at St. Mary's Hospital; 🇺🇸 Green Bay, Wisconsin, United States

Fredericksburg Oncology, Incorporated; 🇺🇸 Fredericksburg, Virginia, United States

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital; 🇺🇸 Minneapolis, Minnesota, United States

CCOP - Wichita; 🇺🇸 Wichita, Kansas, United States

Cancer Center of Kansas, PA - Winfield; 🇺🇸 Winfield, Kansas, United States

Cedar Rapids Oncology Associates; 🇺🇸 Cedar Rapids, Iowa, United States

Mercy Regional Cancer Center at Mercy Medical Center; 🇺🇸 Cedar Rapids, Iowa, United States

St. Luke's Regional Medical Center; 🇺🇸 Sioux City, Iowa, United States

Siouxland Hematology-Oncology Associates, LLP; 🇺🇸 Sioux City, Iowa, United States

Mercy Medical Center - Sioux City; 🇺🇸 Sioux City, Iowa, United States

Cancer Center of Kansas, PA - Chanute; 🇺🇸 Chanute, Kansas, United States

Cancer Center of Kansas, PA - Dodge City; 🇺🇸 Dodge City, Kansas, United States

Cancer Center of Kansas, PA - El Dorado; 🇺🇸 El Dorado, Kansas, United States

Cancer Center of Kansas - Fort Scott; 🇺🇸 Fort Scott, Kansas, United States

Cancer Center of Kansas-Independence; 🇺🇸 Independence, Kansas, United States

Cancer Center of Kansas, PA - Kingman; 🇺🇸 Kingman, Kansas, United States

Lawrence Memorial Hospital; 🇺🇸 Lawrence, Kansas, United States

Cancer Center of Kansas, PA - Liberal; 🇺🇸 Liberal, Kansas, United States

Cancer Center of Kansas, PA - Newton; 🇺🇸 Newton, Kansas, United States

Cancer Center of Kansas, PA - Parsons; 🇺🇸 Parsons, Kansas, United States

Cancer Center of Kansas, PA - Salina; 🇺🇸 Salina, Kansas, 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

Hickman Cancer Center at Bixby Medical Center; 🇺🇸 Adrian, Michigan, United States

Oakwood Cancer Center at Oakwood Hospital and Medical Center; 🇺🇸 Dearborn, Michigan, 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

Van Elslander Cancer Center at St. John Hospital and Medical Center; 🇺🇸 Grosse Pointe Woods, Michigan, United States

Dickinson County Healthcare System; 🇺🇸 Iron Mountain, Michigan, United States

Sparrow Regional Cancer Center; 🇺🇸 Lansing, Michigan, United States

Foote Memorial Hospital; 🇺🇸 Jackson, Michigan, United States

St. Mary Mercy Hospital; 🇺🇸 Livonia, Michigan, United States

Community Cancer Center of Monroe; 🇺🇸 Monroe, Michigan, United States

Mercy Memorial Hospital - Monroe; 🇺🇸 Monroe, Michigan, United States

St. Joseph Mercy Oakland; 🇺🇸 Pontiac, Michigan, United States

Mercy Regional Cancer Center at Mercy Hospital; 🇺🇸 Port Huron, Michigan, United States

Fairview Ridges Hospital; 🇺🇸 Burnsville, Minnesota, United States

St. John Macomb Hospital; 🇺🇸 Warren, Michigan, United States

St. Joseph's Medical Center; 🇺🇸 Brainerd, Minnesota, United States

Mercy and Unity Cancer Center at Mercy Hospital; 🇺🇸 Coon Rapids, Minnesota, United States

Essentia Health - Duluth Clinic; 🇺🇸 Duluth, Minnesota, United States

CCOP - Duluth; 🇺🇸 Duluth, Minnesota, United States

Miller - Dwan Medical Center; 🇺🇸 Duluth, Minnesota, United States

HealthEast Cancer Care at St. John's Hospital; 🇺🇸 Maplewood, Minnesota, United States

Mercy and Unity Cancer Center at Unity Hospital; 🇺🇸 Fridley, Minnesota, United States

Fairview Southdale Hospital; 🇺🇸 Edina, Minnesota, United States

Hutchinson Area Health Care; 🇺🇸 Hutchinson, Minnesota, United States

Minnesota Oncology - Maplewood; 🇺🇸 Maplewood, Minnesota, United States

Hennepin County Medical Center - Minneapolis; 🇺🇸 Minneapolis, Minnesota, United States

Humphrey Cancer Center at North Memorial Outpatient Center; 🇺🇸 Robbinsdale, Minnesota, United States

CCOP - Metro-Minnesota; 🇺🇸 Saint Louis Park, Minnesota, United States

Park Nicollet Cancer Center; 🇺🇸 Saint Louis Park, Minnesota, United States

Benefis Sletten Cancer Institute; 🇺🇸 Great Falls, Montana, United States

Kalispell Regional Medical Center; 🇺🇸 Kalispell, Montana, United States

Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center; 🇺🇸 Hartford, Connecticut, United States

Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center; 🇺🇸 Boise, Idaho, United States

Rapid City Regional Hospital; 🇺🇸 Rapid City, South Dakota, United States

St. Peter's Hospital; 🇺🇸 Helena, Montana, United States

Montana Cancer Center at St. Patrick Hospital and Health Sciences Center; 🇺🇸 Missoula, Montana, United States

Bozeman Deaconess Cancer Center; 🇺🇸 Bozeman, Montana, United States

Montana Cancer Specialists at Montana Cancer Center; 🇺🇸 Missoula, Montana, United States

Hematology-Oncology Centers of the Northern Rockies - Billings; 🇺🇸 Billings, Montana, United States

Saint Joseph Mercy Cancer Center; 🇺🇸 Ann Arbor, Michigan, United States

CCOP - Michigan Cancer Research Consortium; 🇺🇸 Ann Arbor, Michigan, United States

Mayo Clinic Cancer Center; 🇺🇸 Rochester, Minnesota, United States

Seton Cancer Institute at Saint Mary's - Saginaw; 🇺🇸 Saginaw, Michigan, United States

St. Charles Mercy Hospital; 🇺🇸 Oregon, Ohio, United States

Bay Area Cancer Care Center at Bay Area Medical Center; 🇺🇸 Marinette, Wisconsin, United States

Holy Family Memorial Medical Center Cancer Care Center; 🇺🇸 Manitowoc, Wisconsin, United States

Green Bay Oncology, Limited - Sturgeon Bay; 🇺🇸 Sturgeon Bay, Wisconsin, United States

Mid Dakota Clinic, PC; 🇺🇸 Bismarck, North Dakota, United States

St. Mary's Hospital Medical Center - Green Bay; 🇺🇸 Green Bay, Wisconsin, United States

St. Nicholas Hospital; 🇺🇸 Sheboygan, Wisconsin, United States

CCOP - Iowa Oncology Research Association; 🇺🇸 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

John Stoddard Cancer Center at Iowa Lutheran Hospital; 🇺🇸 Des Moines, Iowa, United States

Via Christi Cancer Center at Via Christi Regional Medical Center; 🇺🇸 Wichita, Kansas, United States

St. Vincent Mercy Medical Center; 🇺🇸 Toledo, Ohio, United States

Community Cancer Center; 🇺🇸 Elyria, Ohio, United States

Cancer Center of Kansas, PA - Pratt; 🇺🇸 Pratt, Kansas, United States

Flower Hospital Cancer Center; 🇺🇸 Sylvania, Ohio, United States

Fulton County Health Center; 🇺🇸 Wauseon, Ohio, United States