Stage IV Pancreatic Cancer
Conditions
Brief summary
This randomized phase I/II trial is studying the side effects and best dose of monoclonal antibody therapy when given together with gemcitabine hydrochloride and erlotinib hydrochloride and to see how well they work compared with giving gemcitabine hydrochloride and erlotinib hydrochloride alone as first-line therapy in treating patients with metastatic pancreatic cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies 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. Giving erlotinib hydrochloride and gemcitabine hydrochloride together with monoclonal antibody therapy may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES: I. To assess the appropriate dose of IMC-A12 (cixutumumab) to use in combination with gemcitabine (gemcitabine hydrochloride) and erlotinib (erlotinib hydrochloride). (Phase I) II. To assess progression-free survival in patients with metastatic pancreatic cancer treated with IMC-A12 plus gemcitabine and erlotinib compared to those treated with gemcitabine plus erlotinib alone. (Phase II) III. To assess overall survival in each of the two treatment arms in this group of patients. (Phase II) IV. To assess the total response probability (confirmed and unconfirmed, complete and partial responses) in each of the two treatment arms in the subset of this group of patients with measurable disease. (Phase II) V. To assess the qualitative and quantitative toxicities in each of the two treatment arms in this group of patients. (Phase II) OUTLINE: This is a multicenter, phase I, dose-escalation study of cixutumumab followed by a randomized, phase II study. Patients are initially enrolled into the phase I portion of the study to determine the recommended phase II dose (RPTD) of cixutumumab. Once the RPTD is determined, patients are enrolled into the phase II portion of the study. PHASE I (LIMITED INSTITUTIONS): Patients receive erlotinib hydrochloride orally (PO) once daily on days 1-28, gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15, and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. PHASE II (ALL SWOG MEMBERS): Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive erlotinib hydrochloride, gemcitabine hydrochloride, and cixutumumab at the RPTD as in phase I. ARM II: Patients receive erlotinib hydrochloride and gemcitabine hydrochloride as in arm I. In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Previously collected tumor tissue is obtained for gene expression analyses by RT-PCR, RNA isolation, and cDNA synthesis. Blood samples are collected periodically for correlative studies. Samples are assessed for the potential relationship between gene expression levels, germline polymorphisms, Ras and P13K mutations and progression-free survival and overall survival. After completion of study treatment, patients are followed every 6 months for up to 3 years.
Interventions
BIOLOGICALcixutumumab
Given IV
DRUGerlotinib hydrochloride
Given PO
DRUGgemcitabine hydrochloride
Given IV
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed pancreatic adenocarcinoma * Stage IV disease (any T, any N, M1 \[distant metastases\]) * Unresectable disease * Histologic diagnosis based on a metastatic site must be compatible with pancreatic cancer * Measurable and/or nonmeasurable disease * No endocrine or neuroendocrine tumors, lymphoma of the pancreas, or ampullary cancer * No macroscopic residual disease post-resection as the only site of disease * No clinically significant ascites * No known brain metastases * Patients with neurologic signs or symptoms must undergo brain imaging studies AND studies must be negative for disease * Zubrod performance status 0-1 * ANC ≥ 1,500/mcL * Platelet count ≥ 100,000/mcL * Hemoglobin ≥ 9 g/dL * Leukocytes ≥ 3,000/mcL * Total bilirubin normal * SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN) * Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min * Fasting serum glucose \< 120 mg/dL or below the ULN * Patients with diabetes mellitus who meet this criterion must be on a stable dietary or therapeutic regimen for this condition * INR ≤ 1.5 and PTT ≤ 5 seconds above ULN * Not pregnant or nursing * Fertile patients must use effective contraception * Willing to submit previously collected tumor tissue specimens * No history of allergic reaction attributed to compounds of similar chemical or biological composition to anti-IGF-1R recombinant monoclonal antibody IMC-A12 * No active acute or chronic infections requiring antibiotics * No significant ongoing cardiac problems, including any of the following: * Myocardial infarction within the past 6 months * Uncontrolled hypertension * Unstable angina * Uncontrolled arrhythmia * Congestive heart failure * No known HIV infection * No other prior malignancy, except for the following: * Adequately treated basal cell or squamous cell skin cancer * Carcinoma in situ of the cervix * Adequately treated stage I or II cancer from which the patient is currently in complete remission * Any other cancer from which the patient has been disease-free for 5 years * At least 14 days since prior surgery * At least 28 days since prior radiotherapy for palliation to metastatic sites * Patient must have other untreated metastatic sites that would qualify them for this protocol * At least 6 months since prior adjuvant chemotherapy * No prior chemotherapy, hormonal therapy, immunotherapy, or chemoradiotherapy for advanced or locally advanced pancreatic cancer, including drugs that target either EGFR or IGFR * No plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or any other type of therapy for treatment of cancer * No prior gemcitabine hydrochloride * No prior chimerized or murine monoclonal antibody therapy * No concurrent CYP3A4 inducers including, but not limited to, any of the following: * Rifampicin * Rifabutin * Rifapentine * Phenytoin * Carbamazepine * Phenobarbital * Hypericum perforatum (St. John's wort) * No concurrent CYP3A4 inhibitors including, but not limited to, any of the following: * Atazanavir * Clarithromycin * Indinavir * Itraconazole * Ketoconazole * Nefazodone * Nelfinavir * Ritonavir * Saquinavir * Telithromycin * Troleandomycin * Voriconazole * Concurrent prophylactic low-dose coumadin or low molecular weight heparin allowed provided coagulation criteria are met * Full-dose anticoagulation allowed provided coagulation criteria are met and are under strict control and monitoring
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose Determination | 28 days | Maximum dose of IMC-A12 (in combination with erlotinib and gemcitabine) at which 3/10 or fewer patients have dose-limiting toxicities (DLT). Toxicities graded according to the NCI Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0). DLT apply only during cycle 1 and should be drug-related (possible, probable, or definite). |
| Progression-Free Survival | Up to 3 years | From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 3 years | From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact. |
| Response | Up to 3 years | Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR. |
| Toxicity | Up to 3 years | Number of patients with Grade 3 through 5 adverse events that are related to study drug. Only adverse events that are possibly, probably or definitely related to study drug are reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ph I: Erlotinib + Gemcitabine + IMC-A12 Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m\^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. | 9 |
| Ph II: Erlotinib + Gemcitabine + IMC-A12 Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m\^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. | 57 |
| Ph II: Erlotinib + Gemcitabine Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m\^2 IV days 1, 8 and 15. One cycle = 28 days. | 59 |
| Total | 125 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 6 | 9 |
| Overall Study | Death | 0 | 6 | 5 |
| Overall Study | Not eligible | 1 | 3 | 5 |
| Overall Study | Not protocol specified | 1 | 4 | 2 |
| Overall Study | Progression/Relapse | 7 | 40 | 36 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 7 |
Baseline characteristics
| Characteristic | Total | Ph I: Erlotinib + Gemcitabine + IMC-A12 | Ph II: Erlotinib + Gemcitabine + IMC-A12 | Ph II: Erlotinib + Gemcitabine |
|---|---|---|---|---|
| Age, Continuous | 63 years | 61 years | 63 years | 64 years |
| Race/Ethnicity, Customized Asian | 5 participants | 1 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Black | 18 participants | 2 participants | 10 participants | 6 participants |
| Race/Ethnicity, Customized Hispanic | 9 participants | 1 participants | 3 participants | 5 participants |
| Race/Ethnicity, Customized Non-Hispanic | 108 participants | 8 participants | 53 participants | 47 participants |
| Race/Ethnicity, Customized Unknown | 2 participants | 0 participants | 1 participants | 7 participants |
| Race/Ethnicity, Customized White | 100 participants | 5 participants | 44 participants | 51 participants |
| Sex: Female, Male Female | 62 Participants | 3 Participants | 34 Participants | 25 Participants |
| Sex: Female, Male Male | 63 Participants | 6 Participants | 23 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 9 | 56 / 57 | 57 / 57 |
| serious Total, serious adverse events | 5 / 9 | 34 / 57 | 33 / 57 |
Outcome results
Primary
Maximum Tolerated Dose Determination
Maximum dose of IMC-A12 (in combination with erlotinib and gemcitabine) at which 3/10 or fewer patients have dose-limiting toxicities (DLT). Toxicities graded according to the NCI Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0). DLT apply only during cycle 1 and should be drug-related (possible, probable, or definite).
Time frame: 28 days
Population: Phase I patients receiving at least three doses of the assigned dose during Cycle 1 or whom developed a DLT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib + Gemcitabine + IMC-A12 | Maximum Tolerated Dose Determination | 6 mg/kg IMC-A12 |
Primary
Progression-Free Survival
From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.
Time frame: Up to 3 years
Population: Eligible patients in the Phase II portion of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib + Gemcitabine + IMC-A12 | Progression-Free Survival | 3.6 months |
| Erlotinib + Gemcitabine | Progression-Free Survival | 3.6 months |
Secondary
Overall Survival
From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Time frame: Up to 3 years
Population: Eligible patients in the Phase II portion of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib + Gemcitabine + IMC-A12 | Overall Survival | 7.0 months |
| Erlotinib + Gemcitabine | Overall Survival | 6.5 months |
Secondary
Response
Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.
Time frame: Up to 3 years
Population: Eligible patients in the Phase II portion of the study with measurable disease and adequate response assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib + Gemcitabine + IMC-A12 | Response | 13.7 percentage of participants |
| Erlotinib + Gemcitabine | Response | 15.3 percentage of participants |
Secondary
Toxicity
Number of patients with Grade 3 through 5 adverse events that are related to study drug. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Up to 3 years
Population: Eligible patients who received any treatment and were assessed for toxicity were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Pain - Head/headache | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Blood | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Hypoxia | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Pain - Eye | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - UTI | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Thrombosis/embolism (vascular access-related) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Pain - Abdomen NOS | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Bil. tree | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | PTT (Partial thromboplastin time) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Blood | 1 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Vomiting | 2 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Opportunistic inf associated w/gt=Gr 2 lymphopenia | 1 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Lung | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Syncope (fainting) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Neutrophils/granulocytes (ANC/AGC) | 3 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Pancreas | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Calcium, serum-low (hypocalcemia) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Neuropathy: sensory | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Skin | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Acidosis (metabolic or respiratory) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Nausea | 4 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - UTI | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Stricture/stenosis (incl anastomotic), Stomach | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Muscle weakness, not d/t neuropathy - body/general | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils -Up aerodig | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Cardiac troponin I (cTnI) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Muscle weakness, not d/t neuropathy - Extrem-lower | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Infection-Other (Specify) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Vision-photophobia | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Mucositis/stomatitis (functional/symp) - Oral cav | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Obstruction, GI - Duodenum | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Left ventricular systolic dysfunction | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Sodium, serum-low (hyponatremia) | 1 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Magnesium, serum-low (hypomagnesemia) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Leukocytes (total WBC) | 1 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Cardiac-ischemia/infarction | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Lymphopenia | 1 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Liver dysfunction/failure (clinical) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Vision-blurred vision | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Lymphatics-Other (Specify) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | SVT and nodal arrhythmia - Atrial fibrillation | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Cardiopulmonary arrest, cause unknown (non-fatal) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Adult respiratory distress syndrome (ARDS) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Rash: erythema multiforme | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Dehydration | 3 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | ALT, SGPT (serum glutamic pyruvic transaminase) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Rash: acne/acneiform | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Ventricular arrhythmia - Ventricular fibrillation | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Rash/desquamation | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Dizziness | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Albumin, serum-low (hypoalbuminemia) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Pulmonary/Upper Respiratory-Other (Specify) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Dysphagia (difficulty swallowing) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Diarrhea | 2 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Potassium, serum-low (hypokalemia) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Dyspnea (shortness of breath) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Uric acid, serum-high (hyperuricemia) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Pneumonitis/pulmonary infiltrates | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Edema: limb | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Alkaline phosphatase | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Pleural effusion (non-malignant) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Edema: trunk/genital | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Weight loss | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Platelets | 2 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Fatigue (asthenia, lethargy, malaise) | 4 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Tremor | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Personality/behavioral | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | GGT (gamma-glutamyl transpeptidase) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Allergic reaction/hypersensitivity | 1 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Pericardial effusion (non-malignant) | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Glucose, serum-high (hyperglycemia) | 2 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | AST, SGOT | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Pancreatic endocrine: glucose intolerance | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Hemoglobin | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Thrombosis/thrombus/embolism | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Pancreas, exocrine enzyme deficiency | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Hypotension | 0 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Anorexia | 1 Participants |
| Erlotinib + Gemcitabine + IMC-A12 | Toxicity | Pain - Muscle | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Stricture/stenosis (incl anastomotic), Stomach | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Hypoxia | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Obstruction, GI - Duodenum | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | ALT, SGPT (serum glutamic pyruvic transaminase) | 9 Participants |
| Erlotinib + Gemcitabine | Toxicity | AST, SGOT | 6 Participants |
| Erlotinib + Gemcitabine | Toxicity | Acidosis (metabolic or respiratory) | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Adult respiratory distress syndrome (ARDS) | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Albumin, serum-low (hypoalbuminemia) | 3 Participants |
| Erlotinib + Gemcitabine | Toxicity | Alkaline phosphatase | 4 Participants |
| Erlotinib + Gemcitabine | Toxicity | Allergic reaction/hypersensitivity | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Anorexia | 7 Participants |
| Erlotinib + Gemcitabine | Toxicity | Bilirubin (hyperbilirubinemia) | 5 Participants |
| Erlotinib + Gemcitabine | Toxicity | Calcium, serum-low (hypocalcemia) | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Cardiac troponin I (cTnI) | 3 Participants |
| Erlotinib + Gemcitabine | Toxicity | Cardiac-ischemia/infarction | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Cardiopulmonary arrest, cause unknown (non-fatal) | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Dehydration | 6 Participants |
| Erlotinib + Gemcitabine | Toxicity | Diarrhea | 3 Participants |
| Erlotinib + Gemcitabine | Toxicity | Dizziness | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Dysphagia (difficulty swallowing) | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Dyspnea (shortness of breath) | 2 Participants |
| Erlotinib + Gemcitabine | Toxicity | Edema: limb | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Edema: trunk/genital | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Fatigue (asthenia, lethargy, malaise) | 16 Participants |
| Erlotinib + Gemcitabine | Toxicity | GGT (gamma-glutamyl transpeptidase) | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Glucose, serum-high (hyperglycemia) | 16 Participants |
| Erlotinib + Gemcitabine | Toxicity | Hemoglobin | 9 Participants |
| Erlotinib + Gemcitabine | Toxicity | Hypotension | 3 Participants |
| Erlotinib + Gemcitabine | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Blood | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - UTI | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Bil. tree | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Blood | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Lung | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Pancreas | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Skin | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - UTI | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils -Up aerodig | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Infection-Other (Specify) | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Left ventricular systolic dysfunction | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Leukocytes (total WBC) | 9 Participants |
| Erlotinib + Gemcitabine | Toxicity | Liver dysfunction/failure (clinical) | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Lymphatics-Other (Specify) | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Lymphopenia | 4 Participants |
| Erlotinib + Gemcitabine | Toxicity | Magnesium, serum-low (hypomagnesemia) | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Mucositis/stomatitis (functional/symp) - Oral cav | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Muscle weakness, not d/t neuropathy - Extrem-lower | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Muscle weakness, not d/t neuropathy - body/general | 5 Participants |
| Erlotinib + Gemcitabine | Toxicity | Nausea | 9 Participants |
| Erlotinib + Gemcitabine | Toxicity | Neuropathy: sensory | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Neutrophils/granulocytes (ANC/AGC) | 21 Participants |
| Erlotinib + Gemcitabine | Toxicity | Opportunistic inf associated w/gt=Gr 2 lymphopenia | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | PTT (Partial thromboplastin time) | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Pain - Abdomen NOS | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Pain - Eye | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Pain - Head/headache | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Pain - Muscle | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Pancreas, exocrine enzyme deficiency | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Pancreatic endocrine: glucose intolerance | 6 Participants |
| Erlotinib + Gemcitabine | Toxicity | Pericardial effusion (non-malignant) | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Personality/behavioral | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Platelets | 16 Participants |
| Erlotinib + Gemcitabine | Toxicity | Pleural effusion (non-malignant) | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Pneumonitis/pulmonary infiltrates | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Potassium, serum-low (hypokalemia) | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Pulmonary/Upper Respiratory-Other (Specify) | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Rash/desquamation | 0 Participants |
| Erlotinib + Gemcitabine | Toxicity | Rash: acne/acneiform | 3 Participants |
| Erlotinib + Gemcitabine | Toxicity | Rash: erythema multiforme | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | SVT and nodal arrhythmia - Atrial fibrillation | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Sodium, serum-low (hyponatremia) | 5 Participants |
| Erlotinib + Gemcitabine | Toxicity | Syncope (fainting) | 3 Participants |
| Erlotinib + Gemcitabine | Toxicity | Thrombosis/embolism (vascular access-related) | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Thrombosis/thrombus/embolism | 4 Participants |
| Erlotinib + Gemcitabine | Toxicity | Tremor | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Uric acid, serum-high (hyperuricemia) | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Ventricular arrhythmia - Ventricular fibrillation | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Vision-blurred vision | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Vision-photophobia | 1 Participants |
| Erlotinib + Gemcitabine | Toxicity | Vomiting | 5 Participants |
| Erlotinib + Gemcitabine | Toxicity | Weight loss | 2 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Pain - Eye | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Hypoxia | 2 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Anorexia | 6 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Pain - Head/headache | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Hypotension | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Vision-blurred vision | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Pain - Muscle | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Hemoglobin | 8 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Thrombosis/embolism (vascular access-related) | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Pancreas, exocrine enzyme deficiency | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Glucose, serum-high (hyperglycemia) | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Allergic reaction/hypersensitivity | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Pancreatic endocrine: glucose intolerance | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | GGT (gamma-glutamyl transpeptidase) | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | ALT, SGPT (serum glutamic pyruvic transaminase) | 4 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Pericardial effusion (non-malignant) | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Fatigue (asthenia, lethargy, malaise) | 12 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Thrombosis/thrombus/embolism | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Personality/behavioral | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Edema: trunk/genital | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Alkaline phosphatase | 3 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Platelets | 7 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Edema: limb | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Vision-photophobia | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Pleural effusion (non-malignant) | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Dyspnea (shortness of breath) | 4 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Tremor | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Pneumonitis/pulmonary infiltrates | 2 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Dysphagia (difficulty swallowing) | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Albumin, serum-low (hypoalbuminemia) | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Potassium, serum-low (hypokalemia) | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Dizziness | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | AST, SGOT | 3 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Pulmonary/Upper Respiratory-Other (Specify) | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Diarrhea | 2 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Uric acid, serum-high (hyperuricemia) | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Dehydration | 5 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Adult respiratory distress syndrome (ARDS) | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Rash: acne/acneiform | 2 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Cardiopulmonary arrest, cause unknown (non-fatal) | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Weight loss | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Liver dysfunction/failure (clinical) | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Rash: erythema multiforme | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Lymphatics-Other (Specify) | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Leukocytes (total WBC) | 5 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Cardiac-ischemia/infarction | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Lymphopenia | 5 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Left ventricular systolic dysfunction | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Ventricular arrhythmia - Ventricular fibrillation | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Magnesium, serum-low (hypomagnesemia) | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Infection-Other (Specify) | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | SVT and nodal arrhythmia - Atrial fibrillation | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Mucositis/stomatitis (functional/symp) - Oral cav | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils -Up aerodig | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Cardiac troponin I (cTnI) | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Muscle weakness, not d/t neuropathy - Extrem-lower | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - UTI | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Acidosis (metabolic or respiratory) | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Muscle weakness, not d/t neuropathy - body/general | 3 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Skin | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Sodium, serum-low (hyponatremia) | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Nausea | 6 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Pancreas | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Calcium, serum-low (hypocalcemia) | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Neuropathy: sensory | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Lung | 2 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Rash/desquamation | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Neutrophils/granulocytes (ANC/AGC) | 10 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Obstruction, GI - Duodenum | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Blood | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Stricture/stenosis (incl anastomotic), Stomach | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Opportunistic inf associated w/gt=Gr 2 lymphopenia | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Bil. tree | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | PTT (Partial thromboplastin time) | 0 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - UTI | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Vomiting | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Pain - Abdomen NOS | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Blood | 1 Participants |
| Ph II: Erlotinib + Gemcitabine | Toxicity | Syncope (fainting) | 0 Participants |