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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized Study of the Efficacy and Safety of OncoGel™ Treatment as an Adjunctive Therapy to Systemic Chemotherapy and Concurrent External Beam Radiation Prior to Surgery in Subjects With Localized or Loco-regional Esophageal Cancer

Conditions
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Esophageal Cancer, Adenocarcinoma of the Esophagus, Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: OncoGel (Paclitaxel gel)
* Drug: cisplatin
* Drug: 5-FU
* Radiation: radiation therapy
* Procedure: esophageal resection


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>OncoGel, radiation therapy and systemic chemotherapy (cisplatin plus 5-FU) prior to surgical resection. | Drug: OncoGel (Paclitaxel gel)<br>* 6.3 mg/mL tumor volume, injected into the esophagus during endoscopy, once, before starting chemoradiotherapy<br>Drug: cisplatin<br>* 75 mg/m2 IV (in the vein) once on Day 1 and Day 29<br>Drug: 5-FU<br>* 1000 mg/m2/day, IV (in the vein) for 4 days (96 hours) for two cycles starting on Day 1 and Day 29<br>Radiation: radiation therapy<br>* 50.4 Gy, given in 28 treatments, once per day for 5 1/2 weeks<br>Procedure: esophageal resection<br>* Removal of esophagus after completion of chemotherapy and radiation therapy<br>|
| Active Comparator: Group 2<br>Radiation therapy and systemic chemotherapy (cisplatin plus 5-FU) prior to surgical resection. | Drug: cisplatin<br>* 75 mg/m2 IV (in the vein) once on Day 1 and Day 29<br>Drug: 5-FU<br>* 1000 mg/m2/day, IV (in the vein) for 4 days (96 hours) for two cycles starting on Day 1 and Day 29<br>Radiation: radiation therapy<br>* 50.4 Gy, given in 28 treatments, once per day for 5 1/2 weeks<br>Procedure: esophageal resection<br>* Removal of esophagus after completion of chemotherapy and radiation therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Tumor Response at the Primary Tumor Site Based on Measurement of Primary Tumor Volume (Excluding Involved Lymph Nodes) by Spiral CT | 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 | Screening and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esophagectomy, Esophageal cancer, Localized esophageal cancer, Operable esophageal cancer, Loco-regional esophageal cancer, Phase 2, Paclitaxel, Tumor, Local, Chemotherapy, radiation therapy, surgery, OncoGel, Squamous cell carcinoma of the esophagus