Chemotherapy, Radiation Therapy and Immunotherapy Prior to Surgery in Operable Esophageal Cancer

• Sponsor: SCRI Development Innovations, LLC (Other)
• Overall Status: Completed
• CT.gov ID: NCT00393068
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 62
• Locations: 9
• Arm: 1
• Duration (Months): 53.9
• Patients Per Site: 6.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to see if adding two targeted drugs (bevacizumab and erlotinib) further improves the response to chemotherapy (5-FU, paclitaxel, carboplatin) and radiation therapy in patients with operable esophageal cancer.

Side effects (toxicity) information will also be collected.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Cancer	Drug: Erlotinib; Drug: Bevacizumab; Drug: Paclitaxel; Drug: Carboplatin; Drug: 5-FU; Procedure: Radiation therapy; Procedure: Surgery	Phase 2

Detailed Description

Surgical removal has been the standard treatment for operable esophageal cancer. However, recent studies have shown improved results when patients receive a short course of chemotherapy and radiation therapy prior to surgery.

Prior to surgery study treatment will be given over a 6 weeks (Days 1-42) period. Beginning Day 1 and continuing through Day 35 patients will receive a continuous infusion of 5-FU by vein. A small portable pump will be used to administer this drug into a tube that has been surgically inserted into the patient's vein. On Day 1 and 22 patients will also receive the drugs paclitaxel, carboplatin and bevacizumab by vein. Erlotinib is given by mouth beginning on Day 1 and continuing through Day 45. Patients will receive radiation therapy daily, Monday through Friday, beginning Day 1-35 (approximately 5 weeks).

Surgery will be performed approximately 12-14 weeks after beginning this combined treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Preoperative Concurrent Chemotherapy/Radiation Therapy Plus Bevacizumab/Erlotinib in the Treatment of Localized Esophageal Cancer
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment Prior to surgery study treatment will be given over a 6 weeks (Days 1-42) period. Beginning Day 1 and continuing through Day 35 patients will receive a continuous infusion of 5-FU by vein. A small portable pump will be used to administer this drug into a tube that has been surgically inserted into the patient's vein. On Day 1 and 22 patients will also receive the drugs paclitaxel, carboplatin and bevacizumab by vein. Erlotinib is given by mouth beginning on Day 1 and continuing through Day 45. Patients will receive radiation therapy daily, Monday through Friday, beginning Day 1-35 (approximately 5 weeks). Surgery will be performed approximately 12-14 weeks after beginning this combined treatment.

Drug: Erlotinib; Erlotinib; Other Names: Tarceva ; Drug: Bevacizumab; Bevacizumab; Other Names: Avastin ; Drug: Paclitaxel; Paclitaxel; Other Names: Taxol ; Drug: Carboplatin; Carboplatin; Other Names: Paraplatin ; Drug: 5-FU; 5-FU; Other Names: Fluorouracil ; Procedure: Radiation therapy; Radiation therapy; Procedure: Surgery; Surgery

Outcome Measures

Primary Outcome Measures

1. Pathologic Complete Response (pCR) Rate [18 months]

   pCR was defined as no residual viable cancer found at the primary site or regional lymph nodes upon pathologic review of the surgical specimen for patients who went to surgical resection.

Secondary Outcome Measures

1. Overall Survival [32 months]

   Overall Survival (OS) is defined as the time interval from the start of treatment until death. Patients who remained alive were censored at the date of their last tumor assessment.

2. Progression-Free Survival [36 months]

   Progression-free survival (PFS) was defined as the interval from the date of first treatment until the date of disease progression or death, whichever occurred first. Patients who did not progress were censored at the date of their last tumor assessment.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Clinically confirmed esophageal or gastroesophageal junction cancer stage I, II or III

• No prior treatment for esophageal cancer

• Must be surgical candidate based on stage and location of disease

• Measurable or evaluable disease

• Able to be up and perform self care

• Adequate liver, renal function and bone marrow function

• Patients will have to have a central venous access device placed

• Able to give written informed consent.

• Age 18 or older

Exclusion Criteria:

• Stage IV disease

• Prior cancer treatment for advanced cancer in the last 5 years

• Pregnant or lactating women

• History of stroke, transient ischemic attacks, or acute MI within the past 6 months or any other serious cardiovascular disease

• History of neurological disease

• Recent history of blood in the sputum or vomitus

• Non-healing wounds, ulcer or long bone fractures

• History of bleeding problems or coagulation problems

• History of abdominal fistula, gi perforation or intrabdominal abscess within 6 months

• History of uncontrolled hypertension

Please note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have. You can then decide if you wish to participate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Florida Cancer Specialists	Fort Myers	Florida	United States	33901
2	Integrated Community Oncology Network	Jacksonville	Florida	United States	32256
3	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
4	Consultants in Blood Disorders and Cancer	Louisville	Kentucky	United States	40207
5	Hematology Oncology Associates of Northern NJ	Morristown	New Jersey	United States	07960
6	Aultman Hospital	Canton	Ohio	United States	44710
7	Oncology Hematology Care	Cincinnati	Ohio	United States	45242
8	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee	United States	37404
9	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37023

Sponsors and Collaborators

• SCRI Development Innovations, LLC
• Genentech, Inc.

Investigators

• Principal Investigator: John D Hainsworth, MD, SCRI Development Innovations, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

• Bendell JC, Meluch A, Peyton J, Rubin M, Waterhouse D, Webb C, Burris HA 3rd, Hainsworth JD. A phase II trial of preoperative concurrent chemotherapy/radiation therapy plus bevacizumab/erlotinib in the treatment of localized esophageal cancer. Clin Adv Hematol Oncol. 2012 Jul;10(7):430-7.

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT00393068
• Other Study ID Numbers: SCRI GI 91
• First Posted: Oct 26, 2006
• Last Update Posted: Mar 2, 2022
• Last Verified: Feb 1, 2022

• Additional relevant MeSH terms: Esophageal Neoplasms; Paclitaxel; Bevacizumab; Carboplatin; Fluorouracil; Erlotinib Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Treatment
Arm/Group Description	Prior to surgery study treatment will be given over a 6 weeks (Days 1-42) period. Beginning Day 1 and continuing through Day 35 patients will receive a continuous infusion of 5-FU by vein. A small portable pump will be used to administer this drug into a tube that has been surgically inserted into the patient's vein. On Day 1 and 22 patients will also receive the drugs paclitaxel, carboplatin and bevacizumab by vein. Erlotinib is given by mouth beginning on Day 1 and continuing through Day 45. Patients will receive radiation therapy daily, Monday through Friday, beginning Day 1-35 (approximately 5 weeks). Surgery will be performed approximately 12-14 weeks after beginning this combined treatment.
Period Title: Overall Study
STARTED	62
COMPLETED	44
NOT COMPLETED	18

Baseline Characteristics

Arm/Group Title	Treatment
Arm/Group Description	Prior to surgery study treatment will be given over a 6 weeks (Days 1-42) period. Beginning Day 1 and continuing through Day 35 patients will receive a continuous infusion of 5-FU by vein. A small portable pump will be used to administer this drug into a tube that has been surgically inserted into the patient's vein. On Day 1 and 22 patients will also receive the drugs paclitaxel, carboplatin and bevacizumab by vein. Erlotinib is given by mouth beginning on Day 1 and continuing through Day 45. Patients will receive radiation therapy daily, Monday through Friday, beginning Day 1-35 (approximately 5 weeks). Surgery will be performed approximately 12-14 weeks after beginning this combined treatment.
Overall Participants	62
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64
Sex: Female, Male (Count of Participants)
Female	5 8.1%
Male	57 91.9%
Region of Enrollment (participants) [Number]
United States	62 100%

Outcome Measures

1. Primary Outcome

Title	Pathologic Complete Response (pCR) Rate
Description	pCR was defined as no residual viable cancer found at the primary site or regional lymph nodes upon pathologic review of the surgical specimen for patients who went to surgical resection.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	Prior to surgery study treatment will be given over a 6 weeks (Days 1-42) period. Beginning Day 1 and continuing through Day 35 patients will receive a continuous infusion of 5-FU by vein. A small portable pump will be used to administer this drug into a tube that has been surgically inserted into the patient's vein. On Day 1 and 22 patients will also receive the drugs paclitaxel, carboplatin and bevacizumab by vein. Erlotinib is given by mouth beginning on Day 1 and continuing through Day 45. Patients will receive radiation therapy daily, Monday through Friday, beginning Day 1-35 (approximately 5 weeks). Surgery will be performed approximately 12-14 weeks after beginning this combined treatment.
Measure Participants	62
Count of Participants [Participants]	18 29%

2. Secondary Outcome

Title	Overall Survival
Description	Overall Survival (OS) is defined as the time interval from the start of treatment until death. Patients who remained alive were censored at the date of their last tumor assessment.
Time Frame	32 months

Outcome Measure Data

Analysis Population Description

All patients receiving a dose of study drug.

Arm/Group Title	Treatment
Arm/Group Description	Prior to surgery study treatment will be given over a 6 weeks (Days 1-42) period. Beginning Day 1 and continuing through Day 35 patients will receive a continuous infusion of 5-FU by vein. A small portable pump will be used to administer this drug into a tube that has been surgically inserted into the patient's vein. On Day 1 and 22 patients will also receive the drugs paclitaxel, carboplatin and bevacizumab by vein. Erlotinib is given by mouth beginning on Day 1 and continuing through Day 45. Patients will receive radiation therapy daily, Monday through Friday, beginning Day 1-35 (approximately 5 weeks). Surgery will be performed approximately 12-14 weeks after beginning this combined treatment.
Measure Participants	62
Median (95% Confidence Interval) [months]	30.16

3. Secondary Outcome

Title	Progression-Free Survival
Description	Progression-free survival (PFS) was defined as the interval from the date of first treatment until the date of disease progression or death, whichever occurred first. Patients who did not progress were censored at the date of their last tumor assessment.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

All patients receiving a dose of study drug.

Arm/Group Title	Treatment
Arm/Group Description	Prior to surgery study treatment will be given over a 6 weeks (Days 1-42) period. Beginning Day 1 and continuing through Day 35 patients will receive a continuous infusion of 5-FU by vein. A small portable pump will be used to administer this drug into a tube that has been surgically inserted into the patient's vein. On Day 1 and 22 patients will also receive the drugs paclitaxel, carboplatin and bevacizumab by vein. Erlotinib is given by mouth beginning on Day 1 and continuing through Day 45. Patients will receive radiation therapy daily, Monday through Friday, beginning Day 1-35 (approximately 5 weeks). Surgery will be performed approximately 12-14 weeks after beginning this combined treatment.
Measure Participants	62
Median (95% Confidence Interval) [months]	28.58

Adverse Events

Time Frame	32 months
Arm/Group Title	Treatment
Arm/Group Description	Prior to surgery study treatment will be given over a 6 weeks (Days 1-42) period. Beginning Day 1 and continuing through Day 35 patients will receive a continuous infusion of 5-FU by vein. A small portable pump will be used to administer this drug into a tube that has been surgically inserted into the patient's vein. On Day 1 and 22 patients will also receive the drugs paclitaxel, carboplatin and bevacizumab by vein. Erlotinib is given by mouth beginning on Day 1 and continuing through Day 45. Patients will receive radiation therapy daily, Monday through Friday, beginning Day 1-35 (approximately 5 weeks). Surgery will be performed approximately 12-14 weeks after beginning this combined treatment.
All Cause Mortality
	Treatment
	Affected / at Risk (%)	# Events
Total	29/62 (46.8%)
Serious Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	38/62 (61.3%)
Blood and lymphatic system disorders
Leukocytes	2/62 (3.2%)	2
Cardiac disorders
Supraventricular arrhythmia - atrial fibrillation	2/62 (3.2%)	2
Tachycardia	1/62 (1.6%)	1
Gastrointestinal disorders
Colitis	1/62 (1.6%)	1
Dehydration	10/62 (16.1%)	10
Diarrhea	3/62 (4.8%)	3
Esophagitis	5/62 (8.1%)	6
Ileus	1/62 (1.6%)	1
Mucositis	1/62 (1.6%)	1
Nausea	1/62 (1.6%)	1
GI - Other	1/62 (1.6%)	1
Malnutrition	1/62 (1.6%)	1
Hemorrhage - GI	1/62 (1.6%)	1
General disorders
Fever	1/62 (1.6%)	1
Fatigue	1/62 (1.6%)	1
Death	3/62 (4.8%)	3
Infections and infestations
Febrile Neutropenia	6/62 (9.7%)	6
Sepsis	1/62 (1.6%)	1
Infection	1/62 (1.6%)	2
Nervous system disorders
Syncope	1/62 (1.6%)	1
Confusion	1/62 (1.6%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/62 (1.6%)	1
ARDS	1/62 (1.6%)	1
Surgical and medical procedures
Intraop Injury - Abdominal	2/62 (3.2%)	2
Intraop Injury - Esophagus	1/62 (1.6%)	1
Vascular disorders
Peripheral Arterial Ischemia	1/62 (1.6%)	1
Thrombosis/Thrombus/Embolism	1/62 (1.6%)	1
Other (Not Including Serious) Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	59/62 (95.2%)
Blood and lymphatic system disorders
Leukocytes	40/62 (64.5%)	40
Neutrophils	27/62 (43.5%)	27
Platelets	5/62 (8.1%)	5
Anemia	4/62 (6.5%)	4
Gastrointestinal disorders
Mucositis - Oral Cavity	26/62 (41.9%)	26
Dehydration	19/62 (30.6%)	19
Diarrhea	17/62 (27.4%)	17
Esophagitis	17/62 (27.4%)	17
Anorexia	10/62 (16.1%)	10
Nausea	4/62 (6.5%)	4
Hemorrhage - GI	3/62 (4.8%)	3
General disorders
Fatigue	9/62 (14.5%)	9
Skin and subcutaneous tissue disorders
Rash	9/62 (14.5%)	9
Vascular disorders
Thrombosis/Thrombus/Embolism	4/62 (6.5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The sponsor can review/embargo results communications prior to public release for a period that is >60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.