Clinical trial NCT00667420: Perioperative Panitumumab and Epirubicin, Oxaliplatin and Xeloda (EOX) in Patients With Gastroesophageal Adenocarcinoma
Official title: A Pilot Study of Perioperative Panitumumab in Combination With Epirubicin, Oxaliplatin and Xeloda in Patients With Resectable Gastroesophageal Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Esophageal Adenocarcinoma
Gastric Adenocarcinoma
Keywords: gastric
esophageal
panitumumab
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2008-04-28
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Safety and Tolerability
timeFrame: after 3 cycles of pre-operative chemotherapy (approx 21 days per cycle)
Secondary outcomes:
measure: R0 Resection Rate
timeFrame: time of surgery = after 3 cycles (approx 63 days) of pre-operative EOX-P chemotherapy
measure: Progression-Free Survival
timeFrame: up to 72 months
measure: Pathologic Complete Response Rate
timeFrame: at surgical resection, after 3 cycles pre-operative chemotherapy (approx 63 days)
measure: Overall Survival
timeFrame: duration from enrollment to death (up to 6 years)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: DFCI
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: David P Ryan, MD
role: PRINCIPAL_INVESTIGATOR
References: