Colorectal Cancer
Conditions
Keywords
stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cediranib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving irinotecan together with cediranib may kill more tumor cells. PURPOSE: This phase II clinical trial is studying how well giving irinotecan together with cediranib works in treating patients with metastatic colorectal cancer that did not respond to previous oxaliplatin, fluoropyrimidine, and bevacizumab.
Detailed description
OBJECTIVES: Primary * To determine the proportion of patients who are free from progression at 12 weeks from the start of second-line therapy. Secondary * To determine objective response rate. * To determine overall survival. * To further define the dosing and safety profile of irinotecan hydrochloride and cediranib. OUTLINE: This is a multicenter study. Patients receive irinotecan hydrochloride IV over 90 minutes on days 1 and 8 and oral cediranib once daily on days 1-21. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up every 3 months for up to 2 years from study entry.
Interventions
DRUGcediranib maleate
DRUGirinotecan hydrochloride
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically documented metastatic colorectal cancer * The site of the primary lesion must be or have been confirmed endoscopically, surgically, or radiologically to have been in the colon or rectum * Patients with a history of histologically proven colorectal cancer treated by surgical resection and who develop radiological or clinical evidence of metastatic cancer do not require additional histological or cytological confirmation of metastatic disease unless either of the following are true: * An interval of greater than five years has elapsed between the primary surgery and the development of metastatic disease * The primary cancer was stage I * Must have measurable disease, defined as in at least one dimension (longest dimension to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan * Lesions that are considered nonmeasurable include the following: * Bone lesions * Leptomeningeal disease * Ascites * Pleural/pericardial effusion * Lymphangitis cutis/pulmonis * Abdominal masses that are not confirmed and followed by imaging techniques * Cystic lesions * Must have received one and only one prior regimen for metastatic disease containing oxaliplatin, a fluoropyrimidine, and bevacizumab * Patients who discontinue oxaliplatin due to toxicity are eligible provided they progressed on the fluoropyrimidine component with or without bevacizumab * No known brain metastases PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * ANC ≥ 1,500/μL * Platelet count ≥ 100,000/μL * Hemoglobin ≥ 8 g/dL * Leukocytes ≥ 3,000/mm³ * Calculated creatinine clearance \> 50 mL/min * ALT/AST ≤ 2.5 times upper limit of normal (ULN) * Urine protein \< 1+ protein OR protein \< 1g by 24-hour urine collection and urine protein:creatinine ratio \< 1.0 * Total bilirubin normal * Not pregnant or nursing * Negative pregnancy test * No known end-stage liver disease or active hepatitis * No colonic or small bowel disorders (e.g., inflammatory bowel disease, Crohn's disease, ulcerative colitis) that predispose to diarrhea in which the symptoms are uncontrolled as indicated by baseline pattern of \> 3 watery or soft stools daily in patients without a colostomy or ileostomy * Patients with a colostomy or ileostomy may be entered at investigator discretion * History of hypertension allowed provided it is well controlled (BP \< 150/90 mm Hg) on a regimen of antihypertensive therapy * No concurrent congestive heart failure (New York Heart Association class III or IV) * No significant history of bleeding events or gastrointestinal (GI) perforation * Patients with a history of significant bleeding episodes (e.g., hemoptysis, upper or lower GI bleeding) within 3 months prior to beginning treatment are not eligible unless the source of bleeding has been surgically resected * Patients with a history of GI perforation within 12 months prior to beginning treatment are not eligible * No arterial thrombotic events within 6 months before beginning treatment, including any of the following: * Transient ischemic attack * Cerebrovascular accident * Unstable angina or angina requiring surgical or medical intervention within the past 6 months * Myocardial infarction * No serious or nonhealing wound, ulcer, or bone fracture * Patients with clinically significant peripheral artery disease (i.e., claudication on ambulating less than one block) or any other arterial thrombotic event within 6 months are also ineligible * QTc interval ≤ 470 msec * No personal or family history of long QT syndrome. PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Must have recovered from all acute toxicities of prior therapy for metastatic disease except peripheral neuropathy * At least 6 weeks between the last dose of bevacizumab and the first dose of cediranib * Prior pelvic irradiation is allowed (as long as the measurable lesion is outside the radiotherapy field) * Completed any major surgery ≥ 4 weeks from start of treatment and completed any minor surgery ≥ 1 week prior to start of treatment * Insertion of a vascular access device is not considered major or minor surgery from the standpoint of protocol eligibility * Patients must have fully recovered from the procedure and have a fully healed incision * Patients on full-dose anticoagulation (e.g., warfarin) are eligible provided that both of the following criteria are met: * The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or is on a stable dose of low molecular weight heparin * The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices) * Patients receiving anti-platelet agents are eligible * Patients who are on daily prophylactic aspirin or anticoagulation for atrial fibrillation are eligible * The use of agents with strong proarrhythmic potential is not permitted during the study * Patients who received treatment on CALGB-C80405 and whose treatment failed are eligible for this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Patients Who Are Progression-free at 12 Weeks From the Start of Second-line Therapy | at 12 weeks | The 12 week progression-free rate was defined as the percentage of patients that were alive and progression-free 12 weeks after start of second-line therapy. Disease progression was assessed per modified RECIST criteria, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, in either primary or nodal lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Response Rate | Up to 2 years | The proportion of patients who respond (completely or partially) to each combination regimen will be estimated. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions. |
| Overall Survival | Up to 2 years | Overall Survival (OS) is defined as the time from patient randomization to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method. |
Countries
United States
Participant flow
Recruitment details
Between March 2008 and May 2010, 5 participants were registered.
Participants by arm
| Arm | Count |
|---|---|
| Irinotecan + Cediranib Participants receive irinotecan hydrochloride 125 mg/m\^2 IV over 90 minutes on days 1 and 8 and oral cediranib 20 mg once daily on days 1-21. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Irinotecan + Cediranib |
|---|---|
| Age, Continuous | 69.9 years |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 2 / 4 |
Outcome results
Primary
The Percentage of Patients Who Are Progression-free at 12 Weeks From the Start of Second-line Therapy
The 12 week progression-free rate was defined as the percentage of patients that were alive and progression-free 12 weeks after start of second-line therapy. Disease progression was assessed per modified RECIST criteria, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, in either primary or nodal lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of new lesions.
Time frame: at 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Irinotecan + Cediranib | The Percentage of Patients Who Are Progression-free at 12 Weeks From the Start of Second-line Therapy | 60 percentage of participants |
Secondary
Overall Survival
Overall Survival (OS) is defined as the time from patient randomization to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.
Time frame: Up to 2 years
Population: Study terminated prematurely; due to patient confidentiality concerns this planned analysis was not performed.
Secondary
Radiographic Response Rate
The proportion of patients who respond (completely or partially) to each combination regimen will be estimated. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions.
Time frame: Up to 2 years
Population: Study terminated prematurely; due to patient confidentiality concerns this planned analysis was not performed.