Cancer
Conditions
Keywords
esophageal cancer, Locally advanced esophageal cancer
Brief summary
The overall study objective is to evaluate the dose limiting toxicities and the recommended phase II dose of Panitumumab when combined with the standard of care treatment with cisplatin, fluorouracil and radiation in patients with locally advanced esophageal cancer. The investigators will also be assessing the ability of PET (Positron Emission Tomography) imaging to predict the degree of pathologic response. All patients will have a pre-study FDG (F-18 Fluorodeoxyglucose) PET scan and will receive radiation therapy and chemotherapy over a 35 day period. 4-8 weeks post radiation and chemotherapy patients will be restaged with a PET/CT scan. It is anticipated that approximately 30 patients enrolled will undergo an esophagectomy which is considered standard of care post radiation and chemotherapy. The surgery will allow us to compare this study regimen to the historical standard of care (Cisplatin/fluorouracil chemotherapy with radiation therapy).
Interventions
DRUGPanitumumab
dose escalating 1.5mg/kg or 2.5mg/kg weekly during radiation. Cisplatin on Days 1 and 29, Fluorouracil on Days1-4 and Days 29-32.
Sponsors
Amgen
University of Wisconsin, Madison
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Locally Advanced Esophageal cancer (stages T1N1 or T2-4 any N) 2. Histology must be adenocarcinoma or squamous cell carcinoma 3. Must be surgical candidate based on evaluation by a thoracic surgeon 4. must have adequate organ function as defined by routine lab tests
Exclusion criteria
1. Insitu carcinoma 2. prior chemotherapy for esophageal cancer 3. Metastatic (stage IV disease) 4. Tumors \<5cm from the cricopharyngeus muscle, Tumors with \>75% of tumor located within the stomach 5. Active, uncontrolled cardiac disease 6. subjects with \>Grade 2 neuropathies. -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MTD of Panitumumab in Combination With Cisplatin/Fluorouracil and Radiation for Locally Advanced Esophageal Cancer Determined by Number of Participants Experiencing DLT | approximately 18 weeks | Maximum Tolerated Dose (MTD) will be where 0 of 6 patients experienced Dose Limiting Toxicities (DLT) from start until 28 days after the completion of radiation. The investigator considered DLTs related to the treatment to be: grade 4 hematologic toxicity, grade 3 hematologic toxicity lasting \>7 days, any neutropenic fever, all grade 3 non-hematologic toxicities (excluding alopecia and nausea/vomiting/diarrhea if controlled with antiemetics or anti-diarrheal agents), grade 4 lab abnormality (whether symptomatic or asymptomatic), any treatment related to death, any toxicity associated with 1) any single interruption of radiation \>10 treatment days, 2) \>2 interruptions of radiation per course, 3) a delay in completion of radiation by \>14 days beyond planned treatment schedule, 4) inability to deliver \>80% of planned treatment doses, 5) any infield grade 4 toxicity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Response | 20 weeks. | From therapy initiation through 30 days post surgery. 5.5 weeks of XRT/chemo, 4-8weeks post Radiation (XRT)/Chemo subjects to undergo a surgical resection, and study will be completed 4 weeks post surgery with surgical morbidity and mortality information |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the University of Wisconsin Hospital and Clinics between 2010 and 2013.
Participants by arm
| Arm | Count |
|---|---|
| Dose Level 1 Panitumumab/Cisplatin/Fluorouracil and Radiation therapy Panitumumab: dose escalating 1.5mg/kg or 2.5mg/kg weekly during radiation. Cisplatin on Days 1 and 29, Fluorouracil on Days1-4 and Days 29-32.
1.5mg/kg Panitumumab,80mg/m2 cisplatin, 1000mg/m2 5FU | 5 |
| Dose Level -1 Panitumumab/Cisplatin/Fluorouracil and Radiation therapy Panitumumab: dose escalating 1.5mg/kg or 2.5mg/kg weekly during radiation. Cisplatin on Days 1 and 29, Fluorouracil on Days1-4 and Days 29-32.
1.5mg/kg Panitumumab, 60mg/m2 cisplatin, 750mg/m2 5FU | 6 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | Dose Level 1 | Dose Level -1 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 6 Participants |
| Age, Continuous | 60.3 years | 62.6 years | 61.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 6 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 6 Participants | 11 Participants |
| Region of Enrollment United States | 5 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 5 / 5 | 6 / 6 |
| serious Total, serious adverse events | 2 / 5 | 2 / 6 |
Outcome results
Primary
MTD of Panitumumab in Combination With Cisplatin/Fluorouracil and Radiation for Locally Advanced Esophageal Cancer Determined by Number of Participants Experiencing DLT
Maximum Tolerated Dose (MTD) will be where 0 of 6 patients experienced Dose Limiting Toxicities (DLT) from start until 28 days after the completion of radiation. The investigator considered DLTs related to the treatment to be: grade 4 hematologic toxicity, grade 3 hematologic toxicity lasting \>7 days, any neutropenic fever, all grade 3 non-hematologic toxicities (excluding alopecia and nausea/vomiting/diarrhea if controlled with antiemetics or anti-diarrheal agents), grade 4 lab abnormality (whether symptomatic or asymptomatic), any treatment related to death, any toxicity associated with 1) any single interruption of radiation \>10 treatment days, 2) \>2 interruptions of radiation per course, 3) a delay in completion of radiation by \>14 days beyond planned treatment schedule, 4) inability to deliver \>80% of planned treatment doses, 5) any infield grade 4 toxicity
Time frame: approximately 18 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Level 1 | MTD of Panitumumab in Combination With Cisplatin/Fluorouracil and Radiation for Locally Advanced Esophageal Cancer Determined by Number of Participants Experiencing DLT | 2 Participants |
| Dose Level -1 | MTD of Panitumumab in Combination With Cisplatin/Fluorouracil and Radiation for Locally Advanced Esophageal Cancer Determined by Number of Participants Experiencing DLT | 0 Participants |
Comparison: Dose of Pantiumumab (in combination with Cisplatin \& Fluorouracil - see below)
Comparison: Dose of Cisplatin
Comparison: Dose of Fluorourcil
Secondary
Pathologic Response
From therapy initiation through 30 days post surgery. 5.5 weeks of XRT/chemo, 4-8weeks post Radiation (XRT)/Chemo subjects to undergo a surgical resection, and study will be completed 4 weeks post surgery with surgical morbidity and mortality information
Time frame: 20 weeks.
Population: Data was not collected or analyzed for the pathologic response outcome measure.