Pancreatic Cancer
Conditions
Keywords
Irinotecan, Oxaliplatin, Cetuximab, Advanced or metastatic pancreatic cancer
Brief summary
This phase II trial studies the side effects and how well irinotecan hydrochloride, oxaliplatin and cetuximab work in treating patients with unresectable or metastatic pancreatic cancer. Irinotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving irinotecan hydrochloride together with oxaliplatin and cetuximab may kill more tumor cells.
Detailed description
The investigators will evaluate the side effects and how well irinotecan hydrochloride, oxaliplatin and cetuximab work in treating patients with unresectable or metastatic pancreatic cancer. Irinotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving irinotecan hydrochloride together with oxaliplatin and cetuximab may kill more tumor cells.
Interventions
DRUGIrinotecan, oxaliplatin, and cetuximab
Irinotecan at 90 mg/m2 intravenously every two weeks (administered over 60 minutes) + Oxaliplatin at 60 mg/m2 intravenously every two weeks(administered over 60 minutes) + Cetuximab at 250 mg/m2 intravenously every two weeks (administered over 90 minutes). The treatment interval (one cycle) is every 14 days.
Sponsors
New Mexico Cancer Research Alliance
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
1. All patients, 18 years of age or older, with histology proven pancreatic cancer are eligible. 2. Patients must have a life expectancy of at least 12 weeks. 3. Patients must have a Zubrod performance status of 0-2. 4. Patients must sign an informed consent. 5. Patients should have adequate bone marrow function defined by an absolute peripheral granulocyte count of \>= 1,500 or cells/mm3 and platelet count \>= 60,000/mm3 and absence of a regular red blood cell transfusion requirement. 6. Patients should have adequate hepatic function with a total bilirubin \<= 4.0 mg/dl, could be \<= 10 mg/ml if biliary drainage tube is placed and functional in a newly diagnosed patient, and SGOT or SGPT \<= four times the upper limit of normal, and adequate renal function as defined by a serum creatinine \<= 1.5 x upper limit of normal. 7. For patients that had been treated with one of the study medications will be allowed as long as the treatment did not contain more than 2 study medications at the same time. For example, irinotecan and capecitabine combination will be allowed but not irinotecan and cetuximab. Similarly, gemcitabine with cetuximab will be allowed but not gemcitabine, oxaliplatin and cetuximab. Treated with irinotecan alone followed by oxaliplatin will be allowed but not when irinotecan was in combination with oxaliplatin. 8. Patients are allowed to have up to 2 prior treatments. The protocol will also include chemotherapy naïve patients.
Exclusion criteria
1. Patients with symptomatic brain metastases are excluded from this study. 2. Pregnant women or nursing mothers are not eligible for this trial. Patients of child bearing potential must use adequate contraception. 3. Patients may receive no other concurrent chemotherapy or radiation therapy during this trial. 4. Patients with severe medical problems such as uncontrolled diabetes mellitus or cardiovascular disease or active infections are not eligible for this trial. 5. Known hypersensitivity reaction to any of the study medications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | 2 years | ORR is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1). Target lesions are assessed by computerized tomography (CT): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 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. ORR is the percentage of patients who experienced a CR + the percentage of patients who experienced a PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity | 2 years | Toxicity will be evaluated per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Frequency and severity of adverse events will be tabulated using counts of frequently occurring, serious and severe events of interest (i.e. Grade 3 and Grade 4 adverse events, and Serious Adverse Events (SAEs)). |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited at the University of New Mexico Comprehensive Cancer Center between October, 2008, and December, 2014.
Participants by arm
| Arm | Count |
|---|---|
| Irinotecan, Oxaliplatin, and Cetuximab The goal is to administer at least 4 cycles to each patient, but treatment may stop earlier if the treating physician deems stopping to be in the best interest of the patient. Repeated treatment may be given to patients who benefit (either complete or partial response or stabilization of disease)
Irinotecan, oxaliplatin, and cetuximab: Irinotecan at 90 mg/m2 intravenously every two weeks (administered over 60 minutes) + Oxaliplatin at 60 mg/m2 intravenously every two weeks(administered over 60 minutes) + Cetuximab at 250 mg/m2 intravenously every two weeks (administered over 90 minutes).
The treatment interval (one cycle) is every 14 days. | 58 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Patient did not receive study treatment | 2 |
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Irinotecan, Oxaliplatin, and Cetuximab |
|---|---|
| Age, Continuous | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Region of Enrollment United States | 58 participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 56 / 58 |
| serious Total, serious adverse events | 24 / 58 |
Outcome results
Primary
Overall Response Rate (ORR)
ORR is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1). Target lesions are assessed by computerized tomography (CT): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 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. ORR is the percentage of patients who experienced a CR + the percentage of patients who experienced a PR.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Irinotecan, Oxaliplatin, and Cetuximab | Overall Response Rate (ORR) | 6.9 percentage of participants |
Secondary
Toxicity
Toxicity will be evaluated per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Frequency and severity of adverse events will be tabulated using counts of frequently occurring, serious and severe events of interest (i.e. Grade 3 and Grade 4 adverse events, and Serious Adverse Events (SAEs)).
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Hyperbilirubinemia | 3 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Limb Edema | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Gamma-glutamyltransferase Increased | 2 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Alkaline Phosphatase Increased | 4 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Allergic Reaction/Hypersensitivity | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Anorexia | 2 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Ascites | 2 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Aspartate Aminotransferase Increased | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Constipation | 3 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Creatinine Increased | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Hemoglobin Decreased | 2 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Dehydration | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Diarrhea | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 3 Fatigue | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 3 Gastrointestinal Hemorrhage | 2 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Hyperglycemia | 6 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Hypoalbuminemia | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Hypokalemia | 11 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Hyponatremia | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Hypophosphatemia | 3 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Insomnia | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Leukopenia | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Nausea | 3 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Neutropenia | 3 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Pain - Abdomen | 5 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Pain - Bone | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Decreased Respiration | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Rash | 3 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Syncope | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Thrombocytopenia | 2 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Vomiting | 2 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 4 Encephalopathy | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 4 Fatigue | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 4 Gamma-glutamyltransferase Increased | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 4 Hyperglycemia | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 4 Hypokalemia | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 4 Hypothermia | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 4 Pleural Effusion | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 3 Acidosis | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 3 Anorexia | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 3 Ascites | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 3 Bacteremia | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 3 Cholangitis | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 3 Dehydration | 7 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 3 Diarrhea | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 4 Hyperbilirubinemai | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 4 Hyperglycemia | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 3 Hypotension | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 2 Bowel Obstruction | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 3 Bowel Obstruction | 2 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 3 Gholangitis | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 2 Urinary Tract Infection | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 3 Infection of unknown origin | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 5 Intracranial Hemorrhage | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 2 Mental Status Change | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 4 Muscle Weakness | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 3 Nausea | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 2 Abdominal Pain | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 3 Abdominal Pain | 4 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 2 Pulmonary embolus | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 4 Pulmonary Embolus | 2 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 4 Thrombosis | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 3 Vomiting | 3 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 3 Weight Loss | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | Grade 3 Fatigue | 8 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 4 Renal Failure | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 4 Seizure | 1 participants |
| Irinotecan, Oxaliplatin, and Cetuximab | Toxicity | SAE: Grade 2 Sinus tachycardia | 1 participants |