Pancreatic Cancer
Conditions
Keywords
Stage I, II, III pancreatic adenocarcinoma, Radiographically measurable disease
Brief summary
This study is designed to establish the safety and efficacy of a combination of Erbitux (cetuximab)/Gemzar (gemcitabine)/radiation in patients with pancreatic cancer.
Detailed description
The study treatment for this protocol is * Loading dose of Cetuximab 400 mg/m2 * Weekly Cetuximab 250 mg/m2 * Bi-weekly Gemcitabine 50 mg/m2 * Daily Radiation for 28 fractions * CT scan four weeks after completion of treatment * Evaluation by surgeon for resectability
Interventions
DRUGCetuximab/Gemcitabine
Once weekly Cetuximab, twice weekly Gemcitabine for six weeks
PROCEDURERadiotherapy
Daily radiotherapy for 28 days
Sponsors
Dartmouth-Hitchcock Medical Center
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
* Histologic proof of pancreatic adenocarcinoma * Clinical stage I, II, or III disease * Radiographically measurable disease * Tumor tissue for epidermal growth factor receptor (EGFR) status by immunohistochemistry * Signed protocol consent * Karnofsky performance status of at least 70% * Age \> or = to 18 years * Patients must either not be of child bearing potential or have a negative pregnancy test within 72 hours of treatment. * Absolute neutrophil count (ANC) \> 1500; platelets \> 100,000/ul. * Creatinine \< 1.5 x upper limit of normal (ULN) * Bilirubin \< 1.5 x ULN; AST \< 2.5 x ULN.
Exclusion criteria
* Acute hepatitis or known HIV * Active or uncontrolled infection * Significant history of cardiac disease * Prior therapy which affects or targets the EGF pathway * Prior severe infusion reaction to a monoclonal antibody * Any concurrent chemotherapy not indicated in the study protocol or any other investigational agents * Any previous chemotherapy or abdominal or pelvic radiotherapy * No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or malignancy for which the patient has been disease free for five years. * Any severe pre-existing medical or psychiatric condition, which, in the opinion of the attending physician, will interfere with safe and appropriate treatment and follow-up on study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response of Tumor by RECIST 1.0 Criteria | one month post-therapy | Per RECIST Criteria (v. 1.0) and assessed by CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in sum of the longest diameter (SLD)of target lesions at baseline; Progressive Disease (PD), \>=20% increase in the SLD of target lesions at baseline; Stable Disease (SD), Neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Determined to be Resectable (Eligible for Surgery)After Completion of Therapy | 1 month after completion of treatment | Tumor resectability is based on CT scan and as defined by the American Hepato-Pancreato-Biliary Association Convened Consensus Conference on Resectable and Borderline Resectable Pancreatic Cancer (Callery MP, et al. Ann Surg Oncol 2009; 16:1727-1733): no evidence of superior mesenteric vein (SMV) or portal vein (PV)abutment, distortion, tumor thrombus, or venous encasement, and clear fat planes around celiac axis (CA), hepatic artery (HA), and superior mesenteric artery (SMA). |
| Role of Epidermal Growth Factor Receptor (EGFR) Status in Response to Treatment. | One month post-therapy | Tumor was assessed for EGFR status by immunohistochemistry. EGFR positive and EGRF negative tumor types were evaluated and compared for response to treatment. |
| Number of Participants Assessed for Adverse Events | Participants were followed during treatment and for 30 days after completion of treatment | Adverse events assessed using Common Terminology Criteria for Adverse Events version 3.0 |
| Overall Length of Survival After Therapy | Five years post treatment | Length of survival after therapy in all participants enrolled. |
| Pattern of Failure After Therapy | Five years post treatment | Local recurrence, distant recurrence, or both. |
| Disease-Free Survival After Therapy | Five years post treatment | Time to disease progression after therapy. |
Participant flow
Recruitment details
This was a single-institution study of weekly cetuximab, twice-weekly gemcitabine and intensity modulated radiotherapy in patients with pancreatic ductal adenocarcinoma conducted at Dartmouth-Hitchcock.
Participants by arm
| Arm | Count |
|---|---|
| Cetuximab/Gemcitabine/Radiotherapy weekly cetuximab, twice-weekly gemcitabine and intensity modulated radiotherapy | 37 |
| Total | 37 |
Baseline characteristics
| Characteristic | Cetuximab/Gemcitabine/Radiotherapy |
|---|---|
| Age, Continuous >=65 years | 73.1 years |
| Age, Continuous Between 18 and 65 years | 54.7 years |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / — |
| serious Total, serious adverse events | 22 / 33 |
Outcome results
Primary
Objective Response of Tumor by RECIST 1.0 Criteria
Per RECIST Criteria (v. 1.0) and assessed by CT scan: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in sum of the longest diameter (SLD)of target lesions at baseline; Progressive Disease (PD), \>=20% increase in the SLD of target lesions at baseline; Stable Disease (SD), Neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD.
Time frame: one month post-therapy
Population: Completion of treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cetuximab, Gemcitabine, Radiotherapy | Objective Response of Tumor by RECIST 1.0 Criteria | partial response | 10 participants |
| Cetuximab, Gemcitabine, Radiotherapy | Objective Response of Tumor by RECIST 1.0 Criteria | stable disease | 20 participants |
| Cetuximab, Gemcitabine, Radiotherapy | Objective Response of Tumor by RECIST 1.0 Criteria | progressive disease | 3 participants |
Secondary
Disease-Free Survival After Therapy
Time to disease progression after therapy.
Time frame: Five years post treatment
Population: All evaluable participants who completed treatment, and had confirmed progression of disease.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab, Gemcitabine, Radiotherapy | Disease-Free Survival After Therapy | 9.1 months |
Secondary
Number of Participants Assessed for Adverse Events
Adverse events assessed using Common Terminology Criteria for Adverse Events version 3.0
Time frame: Participants were followed during treatment and for 30 days after completion of treatment
Population: All participants were evaluated for toxicity.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab, Gemcitabine, Radiotherapy | Number of Participants Assessed for Adverse Events | 37 participants |
Secondary
Number of Participants Determined to be Resectable (Eligible for Surgery)After Completion of Therapy
Tumor resectability is based on CT scan and as defined by the American Hepato-Pancreato-Biliary Association Convened Consensus Conference on Resectable and Borderline Resectable Pancreatic Cancer (Callery MP, et al. Ann Surg Oncol 2009; 16:1727-1733): no evidence of superior mesenteric vein (SMV) or portal vein (PV)abutment, distortion, tumor thrombus, or venous encasement, and clear fat planes around celiac axis (CA), hepatic artery (HA), and superior mesenteric artery (SMA).
Time frame: 1 month after completion of treatment
Population: Surviving participants who completed therapy and were determined to be resectable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab, Gemcitabine, Radiotherapy | Number of Participants Determined to be Resectable (Eligible for Surgery)After Completion of Therapy | 26 participants |
Secondary
Overall Length of Survival After Therapy
Length of survival after therapy in all participants enrolled.
Time frame: Five years post treatment
Population: All participants enrolled regardless of evaluability for primary outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab, Gemcitabine, Radiotherapy | Overall Length of Survival After Therapy | 17.3 months |
Secondary
Pattern of Failure After Therapy
Local recurrence, distant recurrence, or both.
Time frame: Five years post treatment
Population: All participants who completed treatment and underwent resection
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cetuximab, Gemcitabine, Radiotherapy | Pattern of Failure After Therapy | number of participants with local recurrence only | 2 participants |
| Cetuximab, Gemcitabine, Radiotherapy | Pattern of Failure After Therapy | number of ppts. with local and distant recurrence | 1 participants |
| Cetuximab, Gemcitabine, Radiotherapy | Pattern of Failure After Therapy | number of ppts. with distant disease recurrence | 17 participants |
| Cetuximab, Gemcitabine, Radiotherapy | Pattern of Failure After Therapy | number of ppts. without recurrence or unknown | 5 participants |
Secondary
Role of Epidermal Growth Factor Receptor (EGFR) Status in Response to Treatment.
Tumor was assessed for EGFR status by immunohistochemistry. EGFR positive and EGRF negative tumor types were evaluated and compared for response to treatment.
Time frame: One month post-therapy
Population: All EGFR (-) subjects who completed therapy were evaluated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab, Gemcitabine, Radiotherapy | Role of Epidermal Growth Factor Receptor (EGFR) Status in Response to Treatment. | 33 percent |
| Cetuximab, Gemcitabine, Radiotherapy in EGFR (+) Tumors | Role of Epidermal Growth Factor Receptor (EGFR) Status in Response to Treatment. | 29 percent |