Trial of Panitumumab/Cisplatin/Fluorouracil Combined With Radiation in Esophageal Cancer

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01128387
• Collaborator: Amgen (Industry)
• Enrollment: 11
• Location: 1
• Arms: 2
• Duration (Months): 77
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The overall study objective is to evaluate the dose limiting toxicities and the recommended phase II dose of Panitumumab when combined with the standard of care treatment with cisplatin, fluorouracil and radiation in patients with locally advanced esophageal cancer. The investigators will also be assessing the ability of PET (Positron Emission Tomography) imaging to predict the degree of pathologic response.

All patients will have a pre-study FDG (F-18 Fluorodeoxyglucose) PET scan and will receive radiation therapy and chemotherapy over a 35 day period. 4-8 weeks post radiation and chemotherapy patients will be restaged with a PET/CT scan. It is anticipated that approximately 30 patients enrolled will undergo an esophagectomy which is considered standard of care post radiation and chemotherapy. The surgery will allow us to compare this study regimen to the historical standard of care (Cisplatin/fluorouracil chemotherapy with radiation therapy).

Condition or Disease	Intervention/Treatment	Phase
Cancer	Drug: Panitumumab	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: Dose escalation studyDose escalation study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of Panitumumab/Cisplatin/Fluorouracil Combined With Radiation Preoperatively for Patients With Locally Advanced Esophageal Cancer
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Oct 1, 2016
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Level -1 Panitumumab/Cisplatin/Fluorouracil and Radiation therapy 1.5mg/kg Panitumumab, 60mg/m2 cisplatin, 750mg/m2 5FU (Fluorouracil)	Drug: Panitumumab; dose escalating 1.5mg/kg or 2.5mg/kg weekly during radiation. Cisplatin on Days 1 and 29, Fluorouracil on Days1-4 and Days 29-32.
Experimental: Dose Level 1 Panitumumab/Cisplatin/Fluorouracil and Radiation therapy 1.5mg/kg Panitumumab, 80mg/m2 cisplatin, 1000mg/m2 5FU (Fluorouracil)	Drug: Panitumumab; dose escalating 1.5mg/kg or 2.5mg/kg weekly during radiation. Cisplatin on Days 1 and 29, Fluorouracil on Days1-4 and Days 29-32.

Outcome Measures

Primary Outcome Measures

1. MTD of Panitumumab in Combination With Cisplatin/Fluorouracil and Radiation for Locally Advanced Esophageal Cancer Determined by Number of Participants Experiencing DLT [approximately 18 weeks]

   Maximum Tolerated Dose (MTD) will be where 0 of 6 patients experienced Dose Limiting Toxicities (DLT) from start until 28 days after the completion of radiation. The investigator considered DLTs related to the treatment to be: grade 4 hematologic toxicity, grade 3 hematologic toxicity lasting >7 days, any neutropenic fever, all grade 3 non-hematologic toxicities (excluding alopecia and nausea/vomiting/diarrhea if controlled with antiemetics or anti-diarrheal agents), grade 4 lab abnormality (whether symptomatic or asymptomatic), any treatment related to death, any toxicity associated with 1) any single interruption of radiation >10 treatment days, 2) >2 interruptions of radiation per course, 3) a delay in completion of radiation by >14 days beyond planned treatment schedule, 4) inability to deliver >80% of planned treatment doses, 5) any infield grade 4 toxicity

Secondary Outcome Measures

1. Pathologic Response [20 weeks.]

   From therapy initiation through 30 days post surgery. 5.5 weeks of XRT/chemo, 4-8weeks post Radiation (XRT)/Chemo subjects to undergo a surgical resection, and study will be completed 4 weeks post surgery with surgical morbidity and mortality information

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Locally Advanced Esophageal cancer (stages T1N1 or T2-4 any N)

2. Histology must be adenocarcinoma or squamous cell carcinoma

3. Must be surgical candidate based on evaluation by a thoracic surgeon

4. must have adequate organ function as defined by routine lab tests

Exclusion Criteria:

1. Insitu carcinoma

2. prior chemotherapy for esophageal cancer

3. Metastatic (stage IV disease)

4. Tumors <5cm from the cricopharyngeus muscle, Tumors with >75% of tumor located within the stomach

5. Active, uncontrolled cardiac disease

6. subjects with >Grade 2 neuropathies. -

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• University of Wisconsin, Madison
• Amgen

Investigators

• Principal Investigator: Mark A Ritter, M.D., Ph.D., University of Wisconsin, Madison

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Wisconsin Carbone Cancer Center

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT01128387
• Other Study ID Numbers: H-2009-0214; RO09211; NCI-2011-00735; A533300; SMPH\HUMAN ONCOLOGY\HUMAN ONCO
• First Posted: May 21, 2010
• Last Update Posted: Dec 9, 2019
• Last Verified: Mar 1, 2018

• Keywords provided by University of Wisconsin, Madison: esophageal cancer; Locally advanced esophageal cancer
• Additional relevant MeSH terms: Esophageal Neoplasms; Panitumumab

Study Results

Participant Flow

Recruitment Details	Participants were recruited from the University of Wisconsin Hospital and Clinics between 2010 and 2013.

Arm/Group Title	Dose Level 1	Dose Level -1
Arm/Group Description	Panitumumab/Cisplatin/Fluorouracil and Radiation therapy Panitumumab: dose escalating 1.5mg/kg or 2.5mg/kg weekly during radiation. Cisplatin on Days 1 and 29, Fluorouracil on Days1-4 and Days 29-32. 1.5mg/kg Panitumumab,80mg/m2 cisplatin, 1000mg/m2 5FU (Fluorouracil)	Panitumumab/Cisplatin/Fluorouracil and Radiation therapy Panitumumab: dose escalating 1.5mg/kg or 2.5mg/kg weekly during radiation. Cisplatin on Days 1 and 29, Fluorouracil on Days1-4 and Days 29-32. 1.5mg/kg Panitumumab,60mg/m2 cisplatin, 750mg/m2 5FU
Period Title: Overall Study
STARTED	5	6
COMPLETED	5	5
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Dose Level 1	Dose Level -1	Total
Arm/Group Description	Panitumumab/Cisplatin/Fluorouracil and Radiation therapy Panitumumab: dose escalating 1.5mg/kg or 2.5mg/kg weekly during radiation. Cisplatin on Days 1 and 29, Fluorouracil on Days1-4 and Days 29-32. 1.5mg/kg Panitumumab,80mg/m2 cisplatin, 1000mg/m2 5FU	Panitumumab/Cisplatin/Fluorouracil and Radiation therapy Panitumumab: dose escalating 1.5mg/kg or 2.5mg/kg weekly during radiation. Cisplatin on Days 1 and 29, Fluorouracil on Days1-4 and Days 29-32. 1.5mg/kg Panitumumab, 60mg/m2 cisplatin, 750mg/m2 5FU	Total of all reporting groups
Overall Participants	5	6	11
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 60%	3 50%	6 54.5%
>=65 years	2 40%	3 50%	5 45.5%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	60.3	62.6	61.5
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	5 100%	6 100%	11 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	5 100%	6 100%	11 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	5 100%	6 100%	11 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	5 100%	6 100%	11 100%

Outcome Measures

1. Primary Outcome

Title	MTD of Panitumumab in Combination With Cisplatin/Fluorouracil and Radiation for Locally Advanced Esophageal Cancer Determined by Number of Participants Experiencing DLT
Description	Maximum Tolerated Dose (MTD) will be where 0 of 6 patients experienced Dose Limiting Toxicities (DLT) from start until 28 days after the completion of radiation. The investigator considered DLTs related to the treatment to be: grade 4 hematologic toxicity, grade 3 hematologic toxicity lasting >7 days, any neutropenic fever, all grade 3 non-hematologic toxicities (excluding alopecia and nausea/vomiting/diarrhea if controlled with antiemetics or anti-diarrheal agents), grade 4 lab abnormality (whether symptomatic or asymptomatic), any treatment related to death, any toxicity associated with 1) any single interruption of radiation >10 treatment days, 2) >2 interruptions of radiation per course, 3) a delay in completion of radiation by >14 days beyond planned treatment schedule, 4) inability to deliver >80% of planned treatment doses, 5) any infield grade 4 toxicity
Time Frame	approximately 18 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Level 1	Dose Level -1
Arm/Group Description	Panitumumab/Cisplatin/Fluorouracil and Radiation therapy Panitumumab: dose escalating 1.5mg/kg or 2.5mg/kg weekly during radiation. Cisplatin on Days 1 and 29, Fluorouracil on Days1-4 and Days 29-32. 1.5mg/kg Panitumumab,80mg/m2 cisplatin, 1000mg/m2 5FU	Panitumumab/Cisplatin/Fluorouracil and Radiation therapy Panitumumab: dose escalating 1.5mg/kg or 2.5mg/kg weekly during radiation. Cisplatin on Days 1 and 29, Fluorouracil on Days1-4 and Days 29-32. 1.5mg/kg Panitumumab,60mg/m2 cisplatin, 750mg/m2 5FU
Measure Participants	5	6
Count of Participants [Participants]	2 40%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dose Level 1, Dose Level -1
	Comments	Dose of Pantiumumab (in combination with Cisplatin & Fluorouracil - see below)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Maximum Tolerated Dose
	Estimated Value	1.5
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dose Level 1, Dose Level -1
	Comments	Dose of Cisplatin
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Maximum Tolerated Dose
	Estimated Value	60
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dose Level 1, Dose Level -1
	Comments	Dose of Fluorourcil
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Maximum Tolerated Dose
	Estimated Value	750
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Pathologic Response
Description	From therapy initiation through 30 days post surgery. 5.5 weeks of XRT/chemo, 4-8weeks post Radiation (XRT)/Chemo subjects to undergo a surgical resection, and study will be completed 4 weeks post surgery with surgical morbidity and mortality information
Time Frame	20 weeks.

Outcome Measure Data

Analysis Population Description

Data was not collected or analyzed for the pathologic response outcome measure.

Arm/Group Title	Dose Level 1	Dose Level -1
Arm/Group Description	Panitumumab/Cisplatin/Fluorouracil and Radiation therapy Panitumumab: dose escalating 1.5mg/kg or 2.5mg/kg weekly during radiation. Cisplatin on Days 1 and 29, Fluorouracil on Days1-4 and Days 29-32. 1.5mg/kg Panitumumab,80mg/m2 cisplatin, 1000mg/m2 5FU	Panitumumab/Cisplatin/Fluorouracil and Radiation therapy Panitumumab: dose escalating 1.5mg/kg or 2.5mg/kg weekly during radiation. Cisplatin on Days 1 and 29, Fluorouracil on Days1-4 and Days 29-32. 1.5mg/kg Panitumumab,60mg/m2 cisplatin, 750mg/m2 5FU
Measure Participants	0	0

Adverse Events

Time Frame	Adverse event data were collected for up to 6 years, 3 months.
Adverse Event Reporting Description	Adverse events were collected at weekly visits.
Arm/Group Title	Dose Level 1		Dose Level -1
Arm/Group Description	Panitumumab/Cisplatin/Fluorouracil and Radiation therapy Panitumumab: dose escalating 1.5mg/kg or 2.5mg/kg weekly during radiation. Cisplatin on Days 1 and 29, Fluorouracil on Days1-4 and Days 29-32. 1.5mg/kg Panitumumab,80mg/m2 cisplatin, 1000mg/m2 5FU		Panitumumab/Cisplatin/Fluorouracil and Radiation therapy Panitumumab: dose escalating 1.5mg/kg or 2.5mg/kg weekly during radiation. Cisplatin on Days 1 and 29, Fluorouracil on Days1-4 and Days 29-32. 1.5mg/kg Panitumumab,60mg/m2 cisplatin, 750mg/m2 5FU
All Cause Mortality
	Dose Level 1		Dose Level -1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/6 (0%)
Serious Adverse Events
	Dose Level 1		Dose Level -1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		2/6 (33.3%)
Blood and lymphatic system disorders
Leukocytes	1/5 (20%)		0/6 (0%)
Lymphopenia	1/5 (20%)		0/6 (0%)
Platelets	2/5 (40%)		0/6 (0%)
Cardiac disorders
Conduction	1/5 (20%)		0/6 (0%)
Supraventricular and nodal arrhythmia	0/5 (0%)		1/6 (16.7%)
Gastrointestinal disorders
Colitis	1/5 (20%)		0/6 (0%)
Dehydration	1/5 (20%)		1/6 (16.7%)
Diarrhea	1/5 (20%)		0/6 (0%)
Hemorrhage	2/5 (40%)		0/6 (0%)
General disorders
Alanine Amiotransferase (ALT)	1/5 (20%)		0/6 (0%)
Aspartate Aminotransferase (AST)	1/5 (20%)		0/6 (0%)
Bilirubin	1/5 (20%)		0/6 (0%)
Infections and infestations
Infection	1/5 (20%)		0/6 (0%)
Metabolism and nutrition disorders
Hyperglycemia	1/5 (20%)		0/6 (0%)
Nervous system disorders
CNS cerebrovascular ischemia	0/5 (0%)		1/6 (16.7%)
Renal and urinary disorders
Renal failure	1/5 (20%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Dose Level 1		Dose Level -1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		6/6 (100%)
Blood and lymphatic system disorders
Platelets	2/5 (40%)		4/6 (66.7%)
Leukocytes	3/5 (60%)		6/6 (100%)
Neutrophils (ANC (Absolute Neutrophil Count))	3/5 (60%)		1/6 (16.7%)
Hemoglobin	5/5 (100%)		3/6 (50%)
Lymphopenia	4/5 (80%)		2/6 (33.3%)
Ear and labyrinth disorders
Tinnitus	1/5 (20%)		0/6 (0%)
Gastrointestinal disorders
Dysphagia	4/5 (80%)		5/6 (83.3%)
Mucositis	2/5 (40%)		4/6 (66.7%)
Esophagitis	5/5 (100%)		0/6 (0%)
Dehydration	1/5 (20%)		5/6 (83.3%)
Diarrhea	4/5 (80%)		0/6 (0%)
Constipation	2/5 (40%)		1/6 (16.7%)
Nausea	3/5 (60%)		1/6 (16.7%)
Thrush	0/5 (0%)		2/6 (33.3%)
Dysgeusia	0/5 (0%)		2/6 (33.3%)
Belching	0/5 (0%)		1/6 (16.7%)
Mouth sores	0/5 (0%)		1/6 (16.7%)
Weight loss	0/5 (0%)		2/6 (33.3%)
Anorexia	0/5 (0%)		1/6 (16.7%)
Esophageal pain	0/5 (0%)		1/6 (16.7%)
General disorders
Fatigue	3/5 (60%)		4/6 (66.7%)
Pain	2/5 (40%)		0/6 (0%)
Metabolism and nutrition disorders
Creatinine	2/5 (40%)		2/6 (33.3%)
Hypoamagnesemia	2/5 (40%)		2/6 (33.3%)
Low sodium (hyponatremia)	3/5 (60%)		2/6 (33.3%)
Low calcium (hypocalcemia)	2/5 (40%)		2/6 (33.3%)
Hyperglycemia	0/5 (0%)		1/6 (16.7%)
Hypophosphatemia	0/5 (0%)		2/6 (33.3%)
Nervous system disorders
Neuropothy	1/5 (20%)		0/6 (0%)
Depression	1/5 (20%)		0/6 (0%)
Syncope	0/5 (0%)		1/6 (16.7%)
Renal and urinary disorders
Nocturia	1/5 (20%)		0/6 (0%)
Skin and subcutaneous tissue disorders
Erythema	0/5 (0%)		0/6 (0%)
Acne	3/5 (60%)		5/6 (83.3%)
Alopecia	1/5 (20%)		0/6 (0%)
Rash - Maculopapular	1/5 (20%)		0/6 (0%)

Limitations/Caveats

The Standard of Care changed during this protocol, and the protocol was terminated prematurely.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.