Gastroesophageal Adenocarcinoma, Adenocarcinoma of the Distal Esophagus, Adenocarcinomas of the Gastroesophageal Junction, Adenocarcinoma of the Proximal Stomach
Conditions
Brief summary
This is an open-label, Phase II, single-stage study evaluating the use of panitumumab, paclitaxel, carboplatin and 5FU as an induction regimen in subjects with gastroesophageal adenocarcinoma. The expectation is that this combination will both increase potential overall survival by incorporating novel biologic therapy in the neoadjuvant setting and decrease potential surgical mortality by eliminating pre-operative radiation therapy.
Interventions
DRUGPanitumumab
Panitumumab 9mg/kg on Days 1, 22, and 43
DRUGPaclitaxel
Paclitaxel 200mg/m2 on Days 1 and 22
DRUGCarboplatin
Carboplatin AUC=6 on Days 1 and 22
DRUG5FU
5FU 225mg/m2/day on Days 1-15 and 22-36
Sponsors
Amgen
Accelerated Community Oncology Research Network
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
* Biopsy-proven adenocarcinoma of the distal esophagus, gastroesophageal junction, or proximal stomach (within 5cm of gastroesophageal junction) * No prior treatment for this disease * AJCC (American Joint Committee on Cancer) clinical stage II to IVA, potentially resectable disease * Measurable disease per RECIST 1.0 criteria * Medically fit for surgery; surgical consultation is encouraged prior to initiation of treatment * ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1 * Male or female; aged equal to or greater than 18 years * Life expectancy of greater than 3 months * Good organ, metabolic, bone marrow, and pulmonary function as specified in the protocol * Functioning central venous access device prior to treatment initiation * Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for at least 6 months following the last administration of panitumumab * Ability to understand and the willingness to sign a written IRB (Institutional Review Board) approved informed consent
Exclusion criteria
* Prior treatment for this disease * History of another primary cancer except curatively treated in situ cervical cancer, curatively resected nonmelanoma skin cancer, or other primary solid tumor curatively treated with no active disease present and no treatment administered for at least 5 years prior to enrollment * History or known presence of central nervous system metastases * History of allergic reactions attributed to compounds similar chemical or biologic composition to panitumumab, paclitaxel, carboplatin, or 5FU * Prior anti-EGFr-antibody therapy or treatment with small molecule EGFr inhibitors * Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved proteins/antibodies within 30 days prior to enrollment * Chronic use of immunosuppressive agents with the exception of corticosteroids * Any investigational agent or therapy within 30 days prior to enrollment * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * History of interstitial lung disease, e.g., pneumonitis or pulmonary fibrosis or any evidence of interstitial lung disease on baseline chest CT scan * History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with study participation or investigational product(s) administration or may interfere with the interpretation of the results * Unwilling or unable to comply with study requirements * Female who tests positive for serum or urine pregnancy test or is breast feeding * Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection * Major surgery within 28 days or minor surgery within 7 days prior to treatment. Placement of a central venous access device less than one day prior to treatment start * Male or female of childbearing potential (women who are post-menopausal less than 52 weeks, not surgically sterilized, or not abstinent) not consenting to use adequate contraception prior to study entry and for at least 6 months following the last administration of panitumumab * Arterial ischemic event (myocardial infarction, stroke) within 3 months prior to enrollment * Ongoing therapeutic anticoagulation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | From the start of study treatment until restaging evaluation performed between days 36 to 43 | The primary endpoint is overall response rate (ORR) as determined per RECIST guidelines version 1.1 from baseline and restaging scans conducted between Days 36 to 43. Response is defined as the occurrence of either Complete Response (CR) or Partial Response (PR) as best response. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. A PR is defined as at least a 30% decrease in the sum of diameters of the target lesions taking as reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Response Rate | At time of surgery (between days 50 to 64) | The patient will be scored as having had a pathologic complete response (pCR) if the routine histologic examination of the resected specimen shows no residual invasive cancer by standard hematoxylin and eosin (H&E) examination. |
| Resection Rate of Surgery | At time of surgery (between days 50 to 64) | The patient will be scored as having an R0 resection, if no invasive cancer is detected involving the margins of the resection by routine microscopic hematoxylin and eosin (H&E)examination, and the operative report indicates complete resection with no residual disease. The patient will be scored as having an R1 resection, if invasive cancer is detected involving the margins of resection by routine microscopic hematoxylin and eosin (H&E) examination, and the operative report indicates complete resection with no residual disease. The patient will be scored as having an R2 resection, if the operative report indicates incomplete resection or gross residual disease. |
| Thirty-day Surgical Mortality | From date of surgery to 30 days after date of surgery | All subjects who have undergone surgical resection will be followed for a 30-day postoperative safety evaluation. Death from any cause within 30 days of the date of surgery will be considered a surgical mortality death. |
| Survival | 2-year survival from first dose of panitumumab | — |
Countries
United States
Participant flow
Recruitment details
10 sites associated with Accelerated Coummunity Oncology Research Network, Inc. (ACORN) or Georgia Center for Oncology Research and Education (GA-CORE)participated in this study. Enrollment started in May 2011 and was closed in November 2011 due to toxicities observed in a similar trial.
Pre-assignment details
Informed consent was obtained from the subject. The Subject underwent a screening period of up to 35 days during which pre-study assessments were completed.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group Panitumumab 9mg/kg on Days 1, 22, and 43
Paclitaxel 200mg/m2 on Days 1 and 22
Carboplatin AUC=6 on Days 1 and 22
5FU 225mg/m2/day on Days 1-15 and 22-36
Treatment group : Panitumumab 9mg/kg on Days 1, 22, and 43
Paclitaxel 200mg/m2 on Days 1 and 22
Carboplatin AUC=6 on Days 1 and 22
5FU 225mg/m2/day on Days 1-15 and 22-36 | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Treatment Group |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age Continuous | 73 years STANDARD_DEVIATION 0 |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Response Rate
The primary endpoint is overall response rate (ORR) as determined per RECIST guidelines version 1.1 from baseline and restaging scans conducted between Days 36 to 43. Response is defined as the occurrence of either Complete Response (CR) or Partial Response (PR) as best response. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. A PR is defined as at least a 30% decrease in the sum of diameters of the target lesions taking as reference the baseline sum diameters.
Time frame: From the start of study treatment until restaging evaluation performed between days 36 to 43
Population: This study was closed due to a notification letter (November 1, 2011) and preliminary results from another trial that included panitumumab as part of combination chemotherapy for gastroesophageal cancer. The study was closed by mutual consent from the Principal Investigator, Sponsor, and Funder.
Secondary
Pathologic Response Rate
The patient will be scored as having had a pathologic complete response (pCR) if the routine histologic examination of the resected specimen shows no residual invasive cancer by standard hematoxylin and eosin (H&E) examination.
Time frame: At time of surgery (between days 50 to 64)
Population: This study was closed due to a notification letter (November 1, 2011) and preliminary results from another trial that included panitumumab as part of combination chemotherapy for gastroesophageal cancer. The study was closed by mutual consent from the Principal Investigator, Sponsor, and Funder.
Secondary
Resection Rate of Surgery
The patient will be scored as having an R0 resection, if no invasive cancer is detected involving the margins of the resection by routine microscopic hematoxylin and eosin (H&E)examination, and the operative report indicates complete resection with no residual disease. The patient will be scored as having an R1 resection, if invasive cancer is detected involving the margins of resection by routine microscopic hematoxylin and eosin (H&E) examination, and the operative report indicates complete resection with no residual disease. The patient will be scored as having an R2 resection, if the operative report indicates incomplete resection or gross residual disease.
Time frame: At time of surgery (between days 50 to 64)
Population: This study was closed due to a notification letter (November 1, 2011) and preliminary results from another trial that included panitumumab as part of combination chemotherapy for gastroesophageal cancer. The study was closed by mutual consent from the Principal Investigator, Sponsor, and Funder.
Secondary
Survival
Time frame: 2-year survival from first dose of panitumumab
Population: This study was closed due to a notification letter (November 1, 2011) and preliminary results from another trial that included panitumumab as part of combination chemotherapy for gastroesophageal cancer. The study was closed by mutual consent from the Principal Investigator, Sponsor, and Funder.
Secondary
Thirty-day Surgical Mortality
All subjects who have undergone surgical resection will be followed for a 30-day postoperative safety evaluation. Death from any cause within 30 days of the date of surgery will be considered a surgical mortality death.
Time frame: From date of surgery to 30 days after date of surgery
Population: This study was closed due to a notification letter (November 1, 2011) and preliminary results from another trial that included panitumumab as part of combination chemotherapy for gastroesophageal cancer. The study was closed by mutual consent from the Principal Investigator, Sponsor, and Funder.