Efficacy and Safety of OncoGel™ Added to Chemotherapy and Radiation Before Surgery in Subjects With Esophageal Cancer

Phase 2

Terminated

Conditions: Esophageal Cancer
Adenocarcinoma of the Esophagus
Squamous Cell Carcinoma

Interventions: Drug: OncoGel (Paclitaxel gel)
Drug: cisplatin
Drug: 5-FU
Radiation: radiation therapy
Procedure: esophageal resection

Registration Number: NCT00573131

Lead Sponsor: Boston Scientific Corporation

Brief Summary: OncoGel is a new experimental drug delivery system that allows the slow continuous release of paclitaxel (an approved intravenous anticancer drug), from a gel (ReGel) over a long period of time. The gel will disappear in 4 to 6 weeks as it releases the paclitaxel.

The protocol is directed towards evaluating the efficacy and safety of paclitaxel delivered as a local, intralesional treatment when used in combination with chemotherapy (cisplatin and 5-FU) and radiation therapy before surgery.

Detailed Description: The primary objective of this study is to evaluate the efficacy of OncoGel given in combination with standard chemotherapy (cisplatin and 5-FU) and radiation therapy in patients with previously untreated, resectable, local or local-regional adenosarcoma or squamous cell carcinoma.

All patients will receive IV cisplatin on Day 1 and Day 29 and IV 5-FU given continuously for 96 hours starting on Day 1 and Day 29. All patients will also receive out-patient radiation therapy for 28 treatments once per day for 5 1/2 weeks starting on Day 1.

Patients randomized to the OncoGel treatment group will have the OncoGel dose injected into their esophageal tumors during an endoscopic procedure just before starting systemic chemotherapy and radiation therapy.

All patients will have CT scans for tumor measurements before starting chemotherapy and 12 weeks later after completion of the radiation therapy and both cycles of chemotherapy.

During the chemotherapy and radiation therapy, physical exams, vital signs, routine blood tests will be performed. Patients will also be asked about their quality of life and ability to swallow.

In-patient surgery will be scheduled 4 to 6 weeks after completion of chemotherapy and radiation therapy. The resected esophagus and lymph nodes will be evaluated for the presence of residual tumor.

Patients will be followed at months 4, 5, 6, and then every 3 Months thereafter for survival and esophageal cancer status and treatment until the last patient enrolled has completed their Month 12 visit.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 137

Inclusion Criteria

Histologically or cytologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus. Stage T2-T3, N any, M0 (no evidence of disseminated cancer except regional involvement which may be designated as "M1a"). No evidence of metastatic disease
Medically able to tolerate major abdominal and/or thoracic surgery
Able to undergo EUS procedure and pass EUS probe through esophageal lumen
Able to receive concurrent systemic chemotherapy (cisplatin and 5-FU) and RT
Clinical management plan includes esophagectomy after completion of two courses of chemoradiation therapy
Karnofsky Performance Status of ≥ 60
Minimum life expectancy of 4 months
Hematologic function
- Absolute neutrophil count (ANC) ≥ 1500/mm3
- Platelet count ≥ 100,000/mm3
- Hemoglobin ≥ 9 g/dL
Hepatic function:
- Total bilirubin < 1.5 X upper limit of normal (ULN)
- AST and ALT < 3 X ULN
- Albumin ≥ 3.0 g/dL or ≥ 2.0 g/dL if the lower level is considered by the investigator to be due to nutritional depletion
Serum creatinine < 1.5 mg/dL and/or creatinine clearance ≥ 65 mL/min
≥ 18 years old
If female, must be non-pregnant, nonlactating, of non-childbearing potential, or using adequate birth control
Capable of understanding and agreeing to fulfill the requirements of the protocol
Sign the IRB/EC approved consent form

Exclusion Criteria

History of anaphylaxis to planned CT contrast agent
Prior esophageal stent insertion, laser, or photodynamic therapy
Prior chest RT or major esophageal surgery
Any prior receipt of cytotoxic chemotherapeutic agents
Prior receipt of other cancer treatments (ie, Chelation therapy), vaccines, or biological response modifiers/growth factors (ie, GM-CSF, IL-2) within the past 4 weeks.
Prior malignancy unless disease free for ≥ 3 years. Note: basal cell/squamous carcinoma of the skin, in situ cervical or breast carcinoma, or superficial transitional cell bladder carcinoma will be allowed. Subjects with a history of low risk prostatic carcinoma (ie, clinical stage 1 or 2a, Gleason score < or = 6 and PSA <10 ng/mL at diagnosis) will be allowed
Significant currently active systemic diseases including uncontrolled diabetes, severe heart disease (New York Heart Association Class III or IV), uncontrolled hypertension, myocardial infarction within 3 months, severe bronchial obstruction, uncontrolled seizure disorder, or peripheral neuropathy greater than CTCAE grade 1
Allergies to any of the active or inactive components of OncoGel (ie, allergies to degradable PLGA [poly(lactide-co-glycolide) sutures])
Receipt of an investigational drug or device within 30 days prior to signing informed consent
Any medical condition or other circumstance that, in the Investigator's opinion, would prevent completion of the study, interfere with analysis of the study results, or potentially adversely affect subject safety
Known esophageal varices

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1	cisplatin	OncoGel, radiation therapy and systemic chemotherapy (cisplatin plus 5-FU) prior to surgical resection.
Group 1	OncoGel (Paclitaxel gel)	OncoGel, radiation therapy and systemic chemotherapy (cisplatin plus 5-FU) prior to surgical resection.
Group 1	esophageal resection	OncoGel, radiation therapy and systemic chemotherapy (cisplatin plus 5-FU) prior to surgical resection.
Group 1	radiation therapy	OncoGel, radiation therapy and systemic chemotherapy (cisplatin plus 5-FU) prior to surgical resection.
Group 2	radiation therapy	Radiation therapy and systemic chemotherapy (cisplatin plus 5-FU) prior to surgical resection.
Group 2	esophageal resection	Radiation therapy and systemic chemotherapy (cisplatin plus 5-FU) prior to surgical resection.
Group 1	5-FU	OncoGel, radiation therapy and systemic chemotherapy (cisplatin plus 5-FU) prior to surgical resection.
Group 2	cisplatin	Radiation therapy and systemic chemotherapy (cisplatin plus 5-FU) prior to surgical resection.
Group 2	5-FU	Radiation therapy and systemic chemotherapy (cisplatin plus 5-FU) prior to surgical resection.

Primary Outcome Measures

Name	Time	Method
Overall Tumor Response at the Primary Tumor Site Based on Measurement of Primary Tumor Volume (Excluding Involved Lymph Nodes) by Spiral CT	Screening and Week 12	Per the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and by Spiral CT assessment: Complete Response (CR) is the disappearance of all target lesions; Partial Response (PR) is a \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (20): University of California San Diego
🇺🇸
San Diego, California, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
University of Chicago Medical Center
🇺🇸
Chicago, Illinois, United States
Indiana University Medical Center
🇺🇸
Indianapolis, Indiana, United States
University of Kansas Medical Center
🇺🇸
Kansas City, Kansas, United States
Thomas Jefferson University
🇺🇸
Philadelphia, Pennsylvania, United States
Baylor University Medical Center
🇺🇸
Dallas, Texas, United States
Digestive Health Specialists of Tyler, Texas
🇺🇸
Tyler, Texas, United States
University Hospital Brno
🇨🇿
Brno, Czechia
Hospital Jablonec nad Nisou
🇨🇿
Jablonec nad Nisou, Czechia
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University of California San Diego
🇺🇸San Diego, California, United States