Efficacy and Safety of OncoGel™ Added to Chemotherapy and Radiation Before Surgery in Subjects With Esophageal Cancer
Condition: Esophageal Cancer; Adenocarcinoma of the Esophagus; Squamous Cell Carcinoma
MeSH terms: Carcinoma, Squamous Cell; Esophageal Neoplasms
Intervention: OncoGel (Paclitaxel gel); cisplatin; 5-FU; radiation therapy; esophageal resection
Intervention description: 6.3 mg/mL tumor volume, injected into the esophagus during endoscopy, once, before starting chemoradiotherapy; 75 mg/m2 IV (in the vein) once on Day 1 and Day 29; 1000 mg/m2/day, IV (in the vein) for 4 days (96 hours) for two cycles starting on Day 1 and Day 29; 50.4 Gy, given in 28 treatments, once per day for 5 1/2 weeks; Removal of esophagus after completion of chemotherapy and radiation therapy
Intervention MeSH terms: Paclitaxel; Cisplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 137.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Esophageal cancer; Localized esophageal cancer; Operable esophageal cancer; Loco-regional esophageal cancer; Esophagectomy; Phase 2; Paclitaxel; Tumor; Local; Chemotherapy; radiation therapy; surgery; OncoGel; Squamous cell carcinoma of the esophagus

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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

          2. Medically able to tolerate major abdominal and/or thoracic surgery

          3. Able to undergo EUS procedure and pass EUS probe through esophageal lumen

          4. Able to receive concurrent systemic chemotherapy (cisplatin and 5-FU) and RT

          5. Clinical management plan includes esophagectomy after completion of two courses of
             chemoradiation therapy

          6. Karnofsky Performance Status of ≥ 60

          7. Minimum life expectancy of 4 months

          8. Hematologic function

               -  Absolute neutrophil count (ANC) ≥ 1500/mm3

               -  Platelet count ≥ 100,000/mm3

               -  Hemoglobin ≥ 9 g/dL

          9. 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

         10. Serum creatinine < 1.5 mg/dL and/or creatinine clearance ≥ 65 mL/min

         11. ≥ 18 years old

         12. If female, must be non-pregnant, nonlactating, of non-childbearing potential, or using
             adequate birth control

         13. Capable of understanding and agreeing to fulfill the requirements of the protocol

         14. Sign the IRB/EC approved consent form

        Exclusion Criteria:

          1. History of anaphylaxis to planned CT contrast agent

          2. Prior esophageal stent insertion, laser, or photodynamic therapy

          3. Prior chest RT or major esophageal surgery

          4. Any prior receipt of cytotoxic chemotherapeutic agents

          5. 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.

          6. 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

          7. 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

          8. Allergies to any of the active or inactive components of OncoGel (ie, allergies to
             degradable PLGA [poly(lactide-co-glycolide) sutures])

          9. Receipt of an investigational drug or device within 30 days prior to signing informed
             consent

         10. 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

         11. Known esophageal varices