Irinotecan, Cisplatin, and Radiation Therapy With or Without Celecoxib in Treating Patients With Stage II, Stage III, or Stage IV Esophageal Cancer - Full Text View

Sponsor:	UNC Lineberger Comprehensive Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00520091

Purpose

RATIONALE: Drugs used in chemotherapy, such as irinotecan and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving chemotherapy and radiation therapy together with celecoxib may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving irinotecan and cisplatin together with radiation therapy with or without celecoxib works in treating patients with stage II, stage III, or stage IV esophageal cancer.

Condition	Intervention	Phase
Esophageal Cancer	Drug: celecoxib Drug: cisplatin Drug: irinotecan hydrochloride Genetic: TdT-mediated dUTP nick end labeling assay Genetic: gene expression analysis Genetic: protein expression analysis Genetic: reverse transcriptase-polymerase chain reaction Other: immunoenzyme technique Other: immunohistochemistry staining method Other: immunologic technique Other: laboratory biomarker analysis Procedure: biopsy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
Official Title:	A Pilot Study of the Biologic Efficacy and Safety of the Addition of Celecoxib to a Program of Induction Chemotherapy and Neo-Adjuvant Chemo-Radiotherapy for the Treatment of Esophageal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders

Drug Information available for: Cisplatin Irinotecan U 101440E Irinotecan hydrochloride Celecoxib

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Rate of cellular apoptosis and proliferation [ Designated as safety issue: No ]
Rate of pathologic complete remission in patients with resectable disease [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety [ Designated as safety issue: Yes ]
Median overall survival of patients with resectable disease [ Designated as safety issue: No ]
Quantitation of expression of cyclooxygenase (COX)-2 and formation of prostaglandin E2 (PGE2) in esophageal cancer [ Designated as safety issue: No ]
Ability of celecoxib to decrease formation of PGE2 in tumor tissue [ Designated as safety issue: No ]
Quantitation of downstream effects of inhibition of COX-2 function [ Designated as safety issue: No ]
Radiographic response rate in patients with unresectable disease [ Designated as safety issue: No ]

Estimated Enrollment:

34

Detailed Description:

OBJECTIVES:

Primary

To measure the rates of cellular apoptosis and proliferation at baseline and during chemoradiotherapy with and without celecoxib using biopsy samples from patients with stage II, III, or IV esophageal cancer.
To determine if an acceptable rate of pathologic complete remission can be achieved in a subset of patients with potentially resectable esophageal cancer.

Secondary

To assess the safety of the addition of daily celecoxib to chemoradiotherapy.
To estimate the median overall survival in a subset of patients with resectable disease.
To quantitate expression of cyclooxygenase (COX)-2 and formation of prostaglandin E2 (PGE2) in patients with esophageal cancer.
To assess the ability of celecoxib to decrease formation of PGE2 in tumor tissue by measuring pre- and post-treatment tumor concentrations of PGE2.
To quantitate downstream effects of inhibition of COX-2 function in the setting of treatment with chemotherapy.
To measure the radiographic response rate in patients with unresectable esophageal cancer.

OUTLINE: This is a multicenter study. Patients are sequentially enrolled into 1 of 2 treatment groups.

Group 1: Patients receive cisplatin IV over 1 hour and irinotecan hydrochloride IV over 90 minutes on days 1, 8, 22, 29, 43, 50, 64, and 71. Patients also undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 43.
Group 2: Patients receive chemoradiotherapy as in group 1. Patients also receive oral celecoxib twice daily beginning 3 days before the initiation of chemotherapy and continuing until the completion of chemoradiotherapy.

In both groups, patients with potentially resectable disease undergo surgery no more than 12 weeks after completion of chemoradiotherapy.

Endoscopic tumor biopsy specimens are collected at baseline and on day 3 of radiotherapy. Samples are analyzed for cyclooxygenase (COX)-2 gene and protein expression; PGE2 secretion; apoptotic activity; caspase-3 activation; cytochrome c translocation; VEGF mRNA quantitation; and cellular proliferation. Laboratory techniques used include RT-PCR, IHC, enzyme immunoassay, TUNEL assay, colorimetric assay, and northern blotting.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 34 patients (8-10 in group 1 and 24 in group 2) will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Biopsy proven squamous cell carcinoma or adenocarcinoma of the esophagus
- Lesions including the gastroesophageal junction allowed provided the tumor involves less than 2 cm of gastric cardia
Meets 1 of the following criteria:
- Clinical stage II, III, or IV disease AND planning to receive chemoradiotherapy either for preoperative or palliative indications (group 1)
  - Suitable candidate for bimodality (palliative intent) or trimodality (curative intent) therapy
- Clinical stage II or III disease AND candidate to receive chemoradiotherapy for preoperative indication followed by planned esophagectomy or esophagogastrectomy (group 2)
  - Suitable candidate for trimodality (curative intent) therapy
No tracheoesophageal fistula on bronchoscopy

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy > 3 months (group 1)
Not pregnant
Adequate nutrition
WBC ≥ 4,000/μL
ANC ≥ 1,500/μL
Platelet count ≥ 100,000/μL
Serum creatinine ≤ 1.5 mg/dL
Bilirubin ≤ 1.5 mg/dL
No other prior or concurrent malignancy other than curatively treated carcinoma in situ of the cervix; localized prostate cancer that was previously treated with local therapy more than 2 years ago with a PSA of less than 4 ng/mL; basal cell carcinoma of the skin; or superficial transitional cell carcinoma of the bladder
- Patients who have had a prior malignancy are eligible if they have been free of disease for ≥ 5 years
No serious medical or psychiatric illnesses that would preclude giving informed consent or otherwise limit survival to less than 2 years
No history of known NSAID-induced gastrointestinal bleeding
No current peptic ulcer disease
No active coronary artery disease
No myocardial infarction or cerebrovascular accident within the past 3 months
No history of refractory congestive heart failure or cardiomyopathy

PRIOR CONCURRENT THERAPY:

More than 1 week since prior major surgery (group 1)
More than 2 weeks since prior major surgery (group 2)
No prior chemotherapy or radiotherapy
More than 30 days since prior cyclooxygenase-2 inhibitors (selective or non-selective), including, but not limited to, any of the following:
- Acetylsalicylic acid (aspirin)
- Piroxicam
- Diclofenac
- Meloxicam
- Indomethacin
- Fenoprofen
- Sulindac
- Flurbiprofen
- Tolmetin
- Ibuprofen
- Celecoxib
- Ketoprofen
- Rofecoxib
- Ketoprofen ER
- Valdecoxib
- Naproxen
- Meclofenamate
- Oxaprozin
- Mefenamic acid
- Etodolac
- Nabumetone
- Ketorolac
No concurrent seizure medications
No concurrent amifostine or other such agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00520091

Sponsors and Collaborators

UNC Lineberger Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Bert H. O'Neil, MD

UNC Lineberger Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000561610, UNC-LCCC-0203
Study First Received:	August 21, 2007
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00520091 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus
stage II esophageal cancer
stage III esophageal cancer
stage IV esophageal cancer

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Diseases
Antineoplastic Agents
Esophageal Neoplasms
Irinotecan
Physiological Effects of Drugs
Neoplasms by Site
Cisplatin
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Celecoxib
Digestive System Neoplasms

Cyclooxygenase Inhibitors
Enzyme Inhibitors
Camptothecin
Pharmacologic Actions
Neoplasms
Digestive System Diseases
Radiation-Sensitizing Agents
Analgesics, Non-Narcotic
Head and Neck Neoplasms
Gastrointestinal Neoplasms
Peripheral Nervous System Agents
Esophageal Diseases
Antirheumatic Agents
Central Nervous System Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on February 08, 2010