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

Sponsored by:	Protherics
Information provided by:	Protherics
ClinicalTrials.gov Identifier:	NCT00573131

Purpose

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.

Condition	Intervention	Phase
Esophageal Cancer Adenocarcinoma of the Esophagus Squamous Cell Carcinoma	Drug: OncoGel (Paclitaxel gel) Drug: cisplatin Drug: 5-FU Radiation: radiation therapy Procedure: esophageal resection	Phase II

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders

Drug Information available for: Cisplatin Paclitaxel Fluorouracil

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind (Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
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

Further study details as provided by Protherics:

Primary Outcome Measures:

Overall tumor response at the primary tumor site based on measurement of primary tumor volume (excluding involved lymph nodes) by spiral CT [ Time Frame: Screening and Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall tumor response at the primary tumor site based on measurement of the longest diameter and largest cross-sectional area of the primary tumor (excluding involved lymph nodes) by spiral CT [ Time Frame: Screening and Week 12 ] [ Designated as safety issue: No ]
Presence and viability of cancer in resection samples (eg, Pathologic complete response (pCR), Pathologic microscopic residual disease (pCRmicro), R0, R1, R2 resections [ Time Frame: After Week 12 and surgical resection ] [ Designated as safety issue: No ]
Absence of metastatic disease at Week 12 (prior to surgery) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Ability to undergo surgical resection [ Time Frame: After Week 12 ] [ Designated as safety issue: No ]
Adverse events including radiation and chemotherapy-related toxicities, and changes in clinical laboratory measurements [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Patient survival [ Time Frame: at least 1 year ] [ Designated as safety issue: No ]
Change from baseline in dysphagia [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Change in quality of life [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Change in Karnofsky and/or ECOG performance status [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	124
Study Start Date:	December 2007
Estimated Study Completion Date:	March 2009
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

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

Arms

Assigned Interventions

Group 1: Experimental

OncoGel, radiation therapy and systemic chemotherapy (cisplatin plus 5-FU) prior to surgical resection.

Drug: OncoGel (Paclitaxel gel)

6.3 mg/mL tumor volume, injected into the esophagus during endoscopy, once, before starting chemoradiotherapy

Drug: cisplatin

75 mg/m2 IV (in the vein) once on Day 1 and Day 29

Drug: 5-FU

1000 mg/m2/day, IV (in the vein) for 4 days (96 hours) for two cycles starting on Day 1 and Day 29

Radiation: radiation therapy

50.4 Gy, given in 28 treatments, once per day for 5 1/2 weeks

Procedure: esophageal resection

Removal of esophagus after completion of chemotherapy and radiation therapy

Group 2: Active Comparator

Radiation therapy and systemic chemotherapy (cisplatin plus 5-FU) prior to surgical resection.

Drug: cisplatin

75 mg/m2 IV (in the vein) once on Day 1 and Day 29

Drug: 5-FU

1000 mg/m2/day, IV (in the vein) for 4 days (96 hours) for two cycles starting on Day 1 and Day 29

Radiation: radiation therapy

50.4 Gy, given in 28 treatments, once per day for 5 1/2 weeks

Procedure: esophageal resection

Removal of esophagus after completion of chemotherapy and radiation therapy

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00573131

Contacts

Contact: Kimberly L Fowler, BA	1-360-874-7595	kimberly.fowler@chiltern.com
Contact: Ozlem Turan, BS	1-760-707-5042	ozlem.turan@chiltern.com

Locations

United States, California
St. Vincent Medical Center	Recruiting
Los Angeles, California, United States, 90057
Contact: Buu Nguyen 213-483-8464 buu_tng@yahoo.com
Contact: Ruby Morris 1-213-483-8464 rmorris@wisemanoncology.com
Principal Investigator: Charles Wiseman, MD
University of California San Diego	Recruiting
San Diego, California, United States, 92093
Contact: Sheryl Diaz 858-822-1847 s1diaz@ucsd.edu
Contact: Sue Ann Castro +1 858 822 5353 scastro@ucsd.edu
Principal Investigator: Tony R Reid, MD PhD
United States, Illinois
University of Chicago Medical Center	Recruiting
Chicago, Illinois, United States, 60637
Contact: Kenisha Allen, RN, OCN 773-834-3137 kallen@medicine.bsd.uchicago.edu
Contact: Livia Szeto 773-834-3137 lszeto@medicine.bsd.uchicago.edu
Principal Investigator: Victoria Villaflor, MD
United States, Indiana
Indiana University Medical Center	Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Maria Poulin 317-274-1113 mmpoulin@iupui.edu
Principal Investigator: John DeWitt, MD
United States, Louisiana
Willis-Knighton Cancer Center	Recruiting
Shreveport, Louisiana, United States, 71103
Contact: Roberta Johnson 318-212-8671 rjohnson1@wkhs.com
Principal Investigator: Sanford Katz, MD
United States, Texas
Digestive Health Specialists of Tyler, Texas	Recruiting
Tyler, Texas, United States, 75701
Contact: Deborah Nelson 903-597-2314 deborahn@dhstyler.com
Principal Investigator: Aaron DuVall, MD
Baylor University Medical Center	Recruiting
Dallas, Texas, United States, 75246
Contact: Mary Sams, RN, MN 214-820-9901 MarySams@BaylorHealth.edu
Principal Investigator: Damien Mallat, MD
Belgium
University Hospital of Ghent	Recruiting
Ghent, Belgium, 9000
Contact: Marc Peeters, MD +32 9 332 2371 marc.peeters@ugent.be
Contact: Tine Derre +32 9 332 5125 tine.derre@ugent.be
Principal Investigator: Marc Peeters, MD
Clinique Saint Joseph	Recruiting
Liege, Belgium, 4000
Contact: Annick Deflandre 32 4 224 89 60 annick.deflandre@chc.be
Principal Investigator: Gauthier Demolin, MD
Czech Republic
University Hospital Brno	Active, not recruiting
Brno, Czech Republic, 62500
University Hospital Motol	Active, not recruiting
Praha, Czech Republic, 150 06
Hospital Jablonec nad Nisou	Recruiting
Jablonec nad Nisou, Czech Republic, 466 60
Contact: Vladimir Nosek, MD +420 483 345 540 nosek@nemjbc.cz
Principal Investigator: Vladimir Nosek, MD
University Hospital Olomouc	Recruiting
Olomouc, Czech Republic, 775 20
Contact: Vomackova +420 588 443 335 cestmir.neoral@fnol.cz
Principal Investigator: Cestmir Neoral, MD CSc
Massaryk's Hospital in Usti nad Labem	Recruiting
Usti nad Labem, Czech Republic, 401 13
Contact: Jiri Stehlik, MD 420 477112 643 jiri.stehlik@mnul.cz
Principal Investigator: Jiri Stehlik, MD
India
Tata Memorial Hospital	Recruiting
Mumbai, India, 400012
Contact: Amol Aher, MS +93 24322082 draaher@yahoo.co.in / hotmail.com
Principal Investigator: CS Pramesh, MS
India, Karnataka
Kidwai Memorial Institute of Oncology	Recruiting
Bangalore, Karnataka, India, 560029
Contact: Shiva Kumar, MS +91 9844127862 skumar_mch@yahoo.co.in
Principal Investigator: S. Krishnamurthy, MS , MCH
India, Kerala
Amrita Institute of Medical Sciences	Recruiting
Kochi, Kerala, India, 682026
Contact: Dinesh Balakrishnan, MS, DNB +91 9846121474 dineshb@aims.amrita.edu
Contact: V G Prasad, BSc +91 9946883997 prasadvg@aims.amrita.edu
Principal Investigator: Puneet Dhar, MS, MCH
India, Maharashtra
Bombay Hospital & Medical Research Centre	Recruiting
Mumbai, Maharashtra, India, 400020
Contact: Beena Pathak +91 9324295628 beena.pathak@gmail.com
Contact: Virendra Rajpurohit, MS +91 9833177678 drvirendra@gmail.com
Principal Investigator: Sanjay Sharma, MS
India, Pune
Deenanath Mangeshkar Hospital	Recruiting
Erandwane, Pune, India, 411004
Contact: Amol Bapaye, MS 91 20 40151163 amolbapaye@vsnl.com
Principal Investigator: Amol Bapaye, MS
India, Tamil Nadu
Meenakshi Mission Hospital and Research Centre	Recruiting
Madurai, Tamil Nadu, India, 625107
Contact: Vinoth Kumar, B.Sc. +91 9842021886 vinothkumar_convey@rediffmail.com
Principal Investigator: Ramesh Ardhanari, MS , MCH
Poland
Samodzielny Publiczny Szpital Kliniczny	Recruiting
Lublin, Poland, 20-081
Contact: Tomasz Skoczylas, MD +48 695 621 774 tomskocz@yahoo.com
Principal Investigator: Grzegorz Wallner, Prof
Samodzielnego Publicznego Szpitala Klinicznego	Recruiting
Szczecin, Poland, 70-111
Contact: Marek Kaminski, MD +48 601 55 38 55 kammar.zs@gmail.com
Principal Investigator: Marek Kaminski, MD

Sponsors and Collaborators

Protherics

Investigators

Study Director:

Nancy L Elstad, MS

Protherics

More Information

Responsible Party:	Protherics ( Nancy Elstad/Head of Clinical Development )
Study ID Numbers:	PR016-CLN-pro003
Study First Received:	December 11, 2007
Last Updated:	December 4, 2008
ClinicalTrials.gov Identifier:	NCT00573131
Health Authority:	United States: Food and Drug Administration; Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment; Czech Republic: State Institute for Drug Control; India: Drugs Controller General of India; Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

Keywords provided by Protherics:

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

Study placed in the following topic categories:

Digestive System Neoplasms
Esophageal disorder
Gastrointestinal Diseases
Esophageal Neoplasms
Squamous cell carcinoma
Carcinoma
Epidermoid carcinoma
Digestive System Diseases
Cisplatin
Paclitaxel

Fluorouracil
Head and Neck Neoplasms
Carcinoma, squamous cell
Gastrointestinal Neoplasms
Esophageal Diseases
Neoplasms, Squamous Cell
Carcinoma, Squamous Cell
Adenocarcinoma
Esophageal neoplasm
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

Mitosis Modulators
Tubulin Modulators
Antimitotic Agents
Antineoplastic Agents, Phytogenic
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009