Mucinous Adenocarcinoma of the Colon, Mucinous Adenocarcinoma of the Rectum, Recurrent Colon Cancer, Recurrent Rectal Cancer, Signet Ring Adenocarcinoma of the Colon, Signet Ring Adenocarcinoma of the Rectum, Stage IV Colon Cancer, Stage IV Rectal Cancer
Conditions
Keywords
Metastatic colon cancer
Brief summary
This phase II trial studies how well panitumumab and combination chemotherapy works in treating patients with metastatic colorectal cancer previously treated with combination chemotherapy and bevacizumab. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving panitumumab and combination chemotherapy together may kill more tumor cells
Detailed description
PRIMARY OBJECTIVES: I. To determine the median progression-free survival in patients treated with leucovorin calcium, fluorouracil, and irinotecan hydrochloride (FOLFIRI) and panitumumab for K-ras and NRAS wild-type, metastatic colorectal carcinoma who have already progressed on FOLFIRI + Bevacizumab. SECONDARY OBJECTIVES: I. To determine the frequency and severity of toxicities of the regimens. II. To determine overall response rate. III. To determine the median overall survival and the overall survival rate at 1 year. OUTLINE: Patients receive panitumumab intravenously (IV) over 60-90 minutes, leucovorin calcium IV over 90 minutes, fluorouracil IV continuously over 46 hours, and irinotecan hydrochloride IV over 90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Interventions
BIOLOGICALpanitumumab
Each vial of panitumumab will contain 20 mL of a sterile protein solution containing a 20-mg/mL solution of panitumumab. The vial will contain approximately 400mg of panitumumab and is for single dose use only.
DRUGirinotecan hydrochloride
Diluted with 5% dextrose (D5W) to a total volume of 500 mL and infused intravenously over 90 minutes. Nothing else should be added to the bag. Patients will be given a dose of 180 mg/M2 by intravenous infusion.
DRUGfluorouracil
Administered intravenously. A bolus of 400 mg/m2 to be followed by a continuous infusion over 46 hrs at a dose of 2400mg/m2.
DRUGleucovorin calcium
Leucovorin will be administered at a dose of 200 mg/m2 over 120 minutes prior to the 5-FU bolus. Leucovorin may be run simultaneously with irinotecan infusion via y-site connection.
Sponsors
Amgen
John Hays
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
* Patients with advanced adenocarcinoma of the colon or rectum not curable with surgery or radiotherapy and have been previously treated for their disease with FOLFIRI plus bevacizumab in the first line metastatic setting; patients will only be eligible if their last line of therapy prior to enrolling onto the study was FOLFIRI and bevacizumab received no more than 6 months prior to enrolling in this study; they should have been treated with FOLFIRI plus bevacizumab until disease progression is radiographically documented * Patients' tumors will need to tested for the K-RAS and N-RAS mutation status; only those patients with wild-type or unmutated K-RAS and N-RAS oncogene are eligible to participate in this study * Provide written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice * Prior cetuximab is allowed in the adjuvant but not in the metastatic setting, but must have been completed at least 6 months before starting this trial * Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 * Life expectancy greater than 12 weeks * No active brain metastasis; previously surgically treated or irradiated lesions are allowed if not clinically active * Has a negative serum pregnancy test within 7 days prior to registration (female patients of childbearing potential) * Ability to understand and willingness to sign a written informed consent * No history of severe reactions to fluorouracil (5-FU), irinotecan (irinotecan hydrochloride), or a monoclonal antibody * Leukocytes \>= 3000/uL * Absolute neutrophil count \>= 1500/uL * Platelets \>= 100,000/uL * Hemoglobin \>= 9 mg/dL * Total bilirubin =\< 1.5 X upper limit of normal (ULN) * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3 X ULN (or \< 5 x ULN with liver metastases) * Creatinine clearance (CrCl) \>= 30 ml/min (Cockroft-Gault equation) * Magnesium \>= lower limit of normal * Measurable disease is required according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria * The effects of Panitumumab on the developing human fetus are unknown; for this reason and because monoclonal antibodies as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and up to 6 months after completing therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Exclusion criteria
* Pregnant or lactating women; women of childbearing potential with either a positive or no pregnancy test at baseline; woman or men of childbearing potential not using a reliable and appropriate contraceptive method; (postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential) * Sexually active males unwilling to practice contraception during the study and 6 months beyond * Uncontrolled intercurrent illness including but not limited to clinically significant cardiac disease not well controlled with medication (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias) or myocardial infarction within the last 12 months, and serious concurrent infections * History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan * KRAS or NRAS mutant tumors * Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as \>= Common Toxicity Criteria \[CTC\] grade 2 \[Common Terminology Criteria for Adverse Events (CTCAE) version 4.0\]) * Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) =\< 1 year * Bevacizumab within the last 4 weeks before starting treatment on trial * Patient is more than 6 months since the last dose of FOLFIRI * Patients who have required toxicity related dose reductions of no less than 50% of the original dose of infusional 5-FU and/or irinotecan during the administration of FOLFIRI + bevacizumab * Prior exposure to panitumumab in any setting * Prior exposure to cetuximab in the metastatic (stage IV) setting * Radiotherapy =\< 14 days prior to enrollment; patients must have recovered from all radiotherapy-related toxicities * Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil, leucovorin (leucovorin calcium), irinotecan, or panitumumab * Treatment for other carcinomas within the last three years, except cured non-melanoma skin and treated in-situ cervical cancer * Participation in any investigational drug study within 4 weeks preceding the start of study treatment * Other serious uncontrolled medical conditions that the investigator feels might compromise study participation * Major surgery within 4 weeks of the start of study treatment, without complete recovery * Unwillingness to give written informed consent * Unwillingness to participate or inability to comply with the protocol for the duration of the study * Patients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and those severely immunocompromised will be excluded; however, no patients will be tested for HIV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Time from study day 1 to the time the patient is first recorded as having disease progression or death, assessed up to 3 years | Continuous variables will be expressed by means, standard deviations and 95% confidence intervals. Estimated using the Kaplan-Meier estimator with confidence interval calculated based on the Brookmeyer-Crowley method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Up to 3 years | Frequencies will be computed for discrete data. Toxicities graded per NCI CTCAE v4.0 grade 3, 4, 5 |
| Proportion of Participants With Overall Response Rate, as Described in RECIST v1.1 Criteria | Up to 3 years | — |
| Overall Survival | Time from study day 1 to the date of death or the last date the patient was known to be alive, assessed up to 3 years | Continuous variables will be expressed by means, standard deviations and 95% confidence intervals. Kaplan-Meier estimator will be used. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Panitumumab, Combination Chemotherapy) 5-Fluorouracil, irinotecan, and panitumumab
panitumumab: Given IV
irinotecan hydrochloride: Given IV
fluorouracil: Given IV
leucovorin calcium: Given IV | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Treatment (Panitumumab, Combination Chemotherapy) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 15 / 16 |
| other Total, other adverse events | 16 / 16 |
| serious Total, serious adverse events | 16 / 16 |
Outcome results
Primary
Progression Free Survival (PFS)
Continuous variables will be expressed by means, standard deviations and 95% confidence intervals. Estimated using the Kaplan-Meier estimator with confidence interval calculated based on the Brookmeyer-Crowley method.
Time frame: Time from study day 1 to the time the patient is first recorded as having disease progression or death, assessed up to 3 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment (Panitumumab, Combination Chemotherapy) | Progression Free Survival (PFS) | 255.921 days to progression |
Secondary
Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0
Frequencies will be computed for discrete data. Toxicities graded per NCI CTCAE v4.0 grade 3, 4, 5
Time frame: Up to 3 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Sleep apnea | 6.3 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | White blood cell decreased | 6.3 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Increased ALT | 6.3 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Increased AST | 6.3 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Diarrhea | 6.3 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Fatigue | 12.5 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Gastrointestional disorders | 6.3 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Hypertension | 12.5 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Hypokalemia | 6.3 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Hypomagnesemia | 12.5 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Hyponatremia | 12.5 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Lymphocyte count decreased | 12.5 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Lymphocyte count increased | 6.3 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Mucositis oral | 25 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Neoplasms benign, malignant and unspecified | 6.3 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Neutrophil count decreased | 6.3 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Palmar-plantar erythrodysesthesia syndrome | 6.3 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Pruritus | 6.3 percentage of patients |
| Treatment (Panitumumab, Combination Chemotherapy) | Frequency and Severity of Toxicities of the Regimens, Graded According to the NCI CTCAE v4.0 | Skin and subcutaneous tissue disorders | 6.3 percentage of patients |
Secondary
Overall Survival
Continuous variables will be expressed by means, standard deviations and 95% confidence intervals. Kaplan-Meier estimator will be used.
Time frame: Time from study day 1 to the date of death or the last date the patient was known to be alive, assessed up to 3 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment (Panitumumab, Combination Chemotherapy) | Overall Survival | 471 days |
Secondary
Proportion of Participants With Overall Response Rate, as Described in RECIST v1.1 Criteria
Time frame: Up to 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Panitumumab, Combination Chemotherapy) | Proportion of Participants With Overall Response Rate, as Described in RECIST v1.1 Criteria | 0.1875 proportion of participants |