Panitumumab, Paclitaxel, Carboplatin and 5FU in the Treatment of Potentially Resectable Gastroesophageal Adenocarcinoma

Phase 2

Terminated

Conditions: Gastroesophageal Adenocarcinoma
Adenocarcinoma of the Distal Esophagus
Adenocarcinomas of the Gastroesophageal Junction
Adenocarcinoma of the Proximal Stomach

Interventions: Drug: Panitumumab
Drug: Paclitaxel
Drug: Carboplatin
Drug: 5FU

Registration Number: NCT01182610

Lead Sponsor: Accelerated Community Oncology Research Network

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment group	5FU	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	Carboplatin	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	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	Paclitaxel	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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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