Esophageal Adenocarcinoma, Gastric Adenocarcinoma
Conditions
Keywords
gastric, esophageal, panitumumab
Brief summary
A pilot study to determine the safety of using perioperative panitumumab with EOX (epirubicin, oxaliplatin, and capecitabine) in patients with adenocarcinoma of the esophagus and stomach.
Interventions
DRUGpanitumumab, epirubicin, oxaliplatin, xeloda
pilot study
Sponsors
Massachusetts General Hospital
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
* Patients must have histologically or cytologically confirmed diagnosis of adenocarcinoma of the stomach, gastroesophageal junction, or lower third of the esophagus, AJCC stage II-IIIB (gastric) or IIA-IVA (esophageal). M1a disease will be included, but not T4 lesions. * No prior radiation or chemotherapy including anti-EGFR or vascular endothelial growth factor (VEGF) antibody or tyrosine kinase inhibitor treatments. * All patients must have staging endoscopic ultrasound (EUS) prior to enrollment. * Men or Women \>18 years of Age * ECOG performance status \<2 (Karnofsky \>60%, see Appendix A). * Cardiac ejection fraction \>45% by echocardiogram or MUGA scan. * Must be able to either swallow pills or have gastrostomy tube in place for administration of enteral medications. * Patients must have normal organ, metabolic and marrow function as defined below: * Hematologic function, as follows: * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L * Platelet count ≥ 100 x 109/L * Hemoglobin ≥ 9.0 g/dL * Renal function, as follows: * Creatinine \< or = 1.5 mg/dL x ULN Hepatic function, as follows: * Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT)\< or = 3 x ULN * Total bilirubin \< 1.5 x ULN Metabolic function, as follows: * Magnesium ≥ lower limit of normal * Calcium \< or = lower limit of normal -Human IgG is known to cross the placental barrier; therefore, Panitumumab may be transmitted from the mother to the developing fetus. In women of childbearing potential, appropriate contraceptive measures must be used during treatment with panitumumab and for 6 months following the last dose of panitumumab. If panitumumab is used during pregnancy or if the patient becomes pregnant while receiving this drug, she should be apprised of the potential risk for loss of the pregnancy or potential hazard to the fetus. 3.1.10 Ability to understand and the willingness to sign and date a written IEC/IRB approved informed consent form.
Exclusion criteria
* Evidence of distant metastatic disease. * T4 tumor on initial staging studies. * History of another primary cancer, except: * Curatively treated in situ cervical cancer * Curatively resected non-melanoma skin cancer * Other primary solid tumor curatively treated with no known active disease present and no treatment administered for ³ 5 years prior to enrollment * Relative or absolute contraindications to surgery which in the opinion of the investigator make the patient a poor candidate for surgical resection. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to panitumumab or other agents used in study. * Subjects requiring chronic use of immunosuppressive agents (e.g., methotrexate, cyclosporine). * 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 the study participation or investigational product(s) administration or may interfere with the interpretation of the results. * Subject unwilling or unable to comply with study requirements. * Women who test positive for serum or urine pregnancy test \< 72 hours before randomization or are breast feeding. * Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection. * Major surgery with 28 days or minor surgery within 14 days of study enrollment. * Men or women of child-bearing potential (women who are post-menopausal \< 52 weeks, not surgically sterilized, or not abstinent) not consenting to use adequate contraception (per institutional standard of care) during the course of the study and after the last investigational product(s) administration (24 weeks for women, 4 weeks for men). * Subjects with \> grade 1 neuropathy at baseline. * Contraindication to port-a-cath placement.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | after 3 cycles of pre-operative chemotherapy (approx 21 days per cycle) | Safety and tolerability were measured by assessing the number of participants able to complete 3 cycles of pre-operative chemotherapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| R0 Resection Rate | time of surgery = after 3 cycles (approx 63 days) of pre-operative EOX-P chemotherapy | percentage of participants who have microscopically negative margins (no tumor at/near the edge of what is resected) at the time of surgical resection |
| Progression-Free Survival | up to 72 months | measured from the first day of treatment to the day when conclusive evidence of new disease is found |
| Pathologic Complete Response Rate | at surgical resection, after 3 cycles pre-operative chemotherapy (approx 63 days) | For patients who undergo complete resection, those who have no evidence of residual viable tumor in the surgical specimen will be declared to have achieved a complete pathologic response (pCR), and the overall percentage of patients with pCR will be determined. |
| Overall Survival | duration from enrollment to death (up to 6 years) | Overall survival (OS) is the duration from start of treatment to time of death from any cause. |
Countries
United States
Participant flow
Recruitment details
Between June 2008 and July 2010, 17 patients with adenocarcinoma of the stomach were accrued to the protocol at the MGH and Dana Farber Cancer Institute.
Participants by arm
| Arm | Count |
|---|---|
| Epirubicin, Oxaliplatin, Capecitabine, Panitumumab Treatment Panitumumab in Combination with Epirubicin, Oxaliplatin and Capecitabine (EOX-P) | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lack of Efficacy | 5 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Epirubicin, Oxaliplatin, Capecitabine, Panitumumab Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 59 years |
| Region of Enrollment United States | 17 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 17 |
| serious Total, serious adverse events | 6 / 17 |
Outcome results
Primary
Safety and Tolerability
Safety and tolerability were measured by assessing the number of participants able to complete 3 cycles of pre-operative chemotherapy
Time frame: after 3 cycles of pre-operative chemotherapy (approx 21 days per cycle)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epirubicin, Oxaliplatin, Capecitabine, Panitumumab Treatment | Safety and Tolerability | 14 participants |
Secondary
Overall Survival
Overall survival (OS) is the duration from start of treatment to time of death from any cause.
Time frame: duration from enrollment to death (up to 6 years)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epirubicin, Oxaliplatin, Capecitabine, Panitumumab Treatment | Overall Survival | NA months |
Secondary
Pathologic Complete Response Rate
For patients who undergo complete resection, those who have no evidence of residual viable tumor in the surgical specimen will be declared to have achieved a complete pathologic response (pCR), and the overall percentage of patients with pCR will be determined.
Time frame: at surgical resection, after 3 cycles pre-operative chemotherapy (approx 63 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epirubicin, Oxaliplatin, Capecitabine, Panitumumab Treatment | Pathologic Complete Response Rate | 0 participants |
Secondary
Progression-Free Survival
measured from the first day of treatment to the day when conclusive evidence of new disease is found
Time frame: up to 72 months
Population: We enrolled 17 patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epirubicin, Oxaliplatin, Capecitabine, Panitumumab Treatment | Progression-Free Survival | 27.2 months | Standard Deviation 24.2 |
Secondary
R0 Resection Rate
percentage of participants who have microscopically negative margins (no tumor at/near the edge of what is resected) at the time of surgical resection
Time frame: time of surgery = after 3 cycles (approx 63 days) of pre-operative EOX-P chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epirubicin, Oxaliplatin, Capecitabine, Panitumumab Treatment | R0 Resection Rate | 52.9 percentage of participants |