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

• Sponsor: Accelerated Community Oncology Research Network (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01182610
• Collaborator: Amgen (Industry)
• Enrollment: 1
• Location: 1
• Arm: 1
• Duration (Months): 11
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gastroesophageal Adenocarcinoma; Adenocarcinoma of the Distal Esophagus; Adenocarcinomas of the Gastroesophageal Junction; Adenocarcinoma of the Proximal Stomach	Drug: Panitumumab; Drug: Paclitaxel; Drug: Carboplatin; Drug: 5FU	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Pre-operative Panitumumab, Paclitaxel, Carboplatin and Continuous Infusion 5FU in the Treatment of Potentially Resectable Gastroesophageal Adenocarcinoma
• Study Start Date: Apr 1, 2011
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Panitumumab; Panitumumab 9mg/kg on Days 1, 22, and 43; Other Names: Vectibix ; Drug: Paclitaxel; Paclitaxel 200mg/m2 on Days 1 and 22; Other Names: Taxol ; Drug: Carboplatin; Carboplatin AUC=6 on Days 1 and 22; Other Names: Paraplatin, CBDCA ; Drug: 5FU; 5FU 225mg/m2/day on Days 1-15 and 22-36; Other Names: 5-fluorouracil

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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.

4. Survival [2-year survival from first dose of panitumumab]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clopton Clinic	Jonesboro	Arkansas	United States	72401

Sponsors and Collaborators

• Accelerated Community Oncology Research Network
• Amgen

Investigators

• Principal Investigator: Robert Hermann, MD, Accelerated Community Oncology Research Network

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Accelerated Community Oncology Research Network
• ClinicalTrials.gov Identifier: NCT01182610
• Other Study ID Numbers: ACORN ARCHESO0611
• First Posted: Aug 17, 2010
• Last Update Posted: Dec 3, 2012
• Last Verified: Nov 1, 2012

• Additional relevant MeSH terms: Adenocarcinoma; Paclitaxel; Carboplatin; Fluorouracil; Panitumumab

Study Results

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 Detail	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.

Arm/Group Title	Treatment Group
Arm/Group Description	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
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment Group
Arm/Group Description	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
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	1 100%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73 (0)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	1 100%
Region of Enrollment (participants) [Number]
United States	1 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Group
Arm/Group Description	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
Measure Participants	0

2. Secondary Outcome

Title	Pathologic Response Rate
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Group
Arm/Group Description	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
Measure Participants	0

3. Secondary Outcome

Title	Resection Rate of Surgery
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Group
Arm/Group Description	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
Measure Participants	0

4. Secondary Outcome

Title	Thirty-day Surgical Mortality
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Group
Arm/Group Description	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
Measure Participants	0

5. Secondary Outcome

Title	Survival
Time Frame	2-year survival from first dose of panitumumab

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Group
Arm/Group Description	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
Measure Participants	0

Adverse Events

Time Frame	Adverse events collected beginning on day 1 of study treatment through the End of Treatment visit (30 days post-operative, 6 weeks from last treatment administration if treatment failure, or 30 days from last dose of study treatment if early withdrawal).
Adverse Event Reporting Description	Systematic Assessment- subjects were assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Arm/Group Title	Treatment Group: Panitumumab, Paclitaxel, Carboplatin and 5FU
Arm/Group Description	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
All Cause Mortality
	Treatment Group: Panitumumab, Paclitaxel, Carboplatin and 5FU
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment Group: Panitumumab, Paclitaxel, Carboplatin and 5FU
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Blood and lymphatic system disorders
Neutropenia	1/1 (100%)
Gastrointestinal disorders
Diarrhoea	1/1 (100%)
General disorders
Mucosal inflammation	1/1 (100%)
Other (Not Including Serious) Adverse Events
	Treatment Group: Panitumumab, Paclitaxel, Carboplatin and 5FU
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Blood and lymphatic system disorders
Anaemia	1/1 (100%)
Neutropenia	1/1 (100%)
Thrombocytopenia	1/1 (100%)
Eye disorders
Abnormal sensation in eye	1/1 (100%)
Gastrointestinal disorders
Abdominal pain	1/1 (100%)
Diarrhoea	1/1 (100%)
Dry mouth	1/1 (100%)
Dysphagia	1/1 (100%)
Nausea	1/1 (100%)
Stomatitis	1/1 (100%)
Vomiting	1/1 (100%)
General disorders
Fatigue	1/1 (100%)
Generalised oedema	1/1 (100%)
Mucosal inflammation	1/1 (100%)
Pyrexia	1/1 (100%)
Investigations
Weight Decreased	1/1 (100%)
Metabolism and nutrition disorders
Decreased appetite	1/1 (100%)
Hypoalbuminemia	1/1 (100%)
Hypocalcaemia	1/1 (100%)
Hypokalaemia	1/1 (100%)
Nervous system disorders
Depressed level of consiciousness	1/1 (100%)
Dizziness	1/1 (100%)
Dysgeusia	1/1 (100%)
Neuralgia	1/1 (100%)
Paraesthesia	1/1 (100%)
Syncope	1/1 (100%)
Psychiatric disorders
Anxiety	1/1 (100%)
Delirium	1/1 (100%)
Depression	1/1 (100%)
Insomnia	1/1 (100%)
Renal and urinary disorders
Urinary retention	1/1 (100%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/1 (100%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform	1/1 (100%)
Exfoliative rash	1/1 (100%)
Vascular disorders
Hypotension	1/1 (100%)

Limitations/Caveats

This study was closed due to notification and preliminary results from a trial including panitumumab as part of combination chemotherapy for gastroesophageal cancer. The study was closed by mutual consent from the PI, Sponsor, and Funder.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Prior to publication or presentation of Sponsored Research results, Researcher agrees to provide Amgen 60 days to review a manuscript and 15 days to review any poster presentation, abstract or other written or oral materials derived from a Study. If Amgen requests in writing, the Researcher shall withhold material an additional 60 days. Amgen reserves the right to remove confidential information from any publications. The Researcher shall reference Amgen's support of the Study in any material.