Clinical trial NCT00573131: Efficacy and Safety of OncoGel™ Added to Chemotherapy and Radiation Before Surgery in Subjects With Esophageal Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Esophageal Cancer
Adenocarcinoma of the Esophagus
Squamous Cell Carcinoma
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
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
First posted: 2007-12-13
Enrollment: 137
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Tumor Response at the Primary Tumor Site Based on Measurement of Primary Tumor Volume (Excluding Involved Lymph Nodes) by Spiral CT
timeFrame: Screening and Week 12
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Tyler
country: United States
facility: Digestive Health Specialists of Tyler, Texas
state: Texas
city: Brno
country: Czechia
facility: University Hospital Brno
city: Jablonec nad Nisou
country: Czechia
facility: Hospital Jablonec nad Nisou
city: Olomouc
country: Czechia
facility: University Hospital Olomouc
city: Praha
country: Czechia
facility: University Hospital Motol
city: Usti nad Labem
country: Czechia
facility: Massaryk's Hospital in Usti nad Labem
city: Bangalore
country: India
facility: Kidwai Memorial Institute of Oncology
state: Karnataka
city: Kochi
country: India
facility: Amrita Institute of Medical Sciences
state: Kerala
city: Mumbai
country: India
facility: Bombay Hospital & Medical Research Centre
state: Maharashtra
city: Erandwane
country: India
facility: Deenanath Mangeshkar Hospital
state: Pune
city: Madurai
country: India
facility: Meenakshi Mission Hospital and Research Centre
state: Tamil Nadu
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny
city: Szczecin
country: Poland
facility: Samodzielnego Publicznego Szpitala Klinicznego
Study officials:
affiliation: Boston Scientific Corporation
name: Kirk D Fowers, PhD
role: STUDY_DIRECTOR
References:
citation: DeWitt JM, Murthy SK, Ardhanari R, DuVall GA, Wallner G, Litka P, Daugherty C, Fowers K. EUS-guided paclitaxel injection as an adjunctive therapy to systemic chemotherapy and concurrent external beam radiation before surgery for localized or locoregional esophageal cancer: a multicenter prospective randomized trial. Gastrointest Endosc. 2017 Jul;86(1):140-149. doi: 10.1016/j.gie.2016.11.017. Epub 2016 Nov 24.