Pilot Study Celecoxib Added to Induction Chemotherapy and Neo-Adjuvant Chemo-Radiotherapy for Esophageal Cancer

Condition(s) targeted: Esophageal Cancer

Intervention: Celecoxib (Drug); radiation (Procedure); irinotecan (Drug); Cisplatin (Drug)

Phase: N/A

Status: No longer recruiting

Sponsored by: UNC Lineberger Comprehensive Cancer Center

Official(s) and/or principal investigator(s):
Bert O'Neil, MD, Principal Investigator, Affiliation: The University of North Carolina at Chapel Hill

The purpose of this research study is to determine the safety of adding celecoxib (Celebrex), an anti-inflammatory medication, to a standard program of pre-surgical (neo-adjuvant) chemotherapy and radiation therapy. We believe that celecoxib and other anti-inflammatory drugs have effects on cancer cells which might make chemotherapy and radiation more effective in killing cancer.

Official title: LCCC 0203: 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

Study design: Interventional, Treatment, Non-Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

To measure the rates of cellular apoptosis and proliferation in esophageal cancers from biopsy samples pre-study and during chemoradiation with and without celecoxib therapy.

To assess the safety of the addition of daily celecoxib to patients treated with neo-adjuvant chemoradiation.

Secondary outcome:

To quantitate expression of cyclooxygenase 2 and formation of prostaglandin E2 in esophageal carcinomas.

To assess the ability of celecoxib to decrease formation of prostaglandin E2 (PGE2) in tumor tissue by measuring pre- and post-treatment tumor concentrations of PGE2.

To quantitate downstream effects of inhibition of cyclooxygenase 2 function in the setting of treatment with chemotherapy.

To assess the rate of complete pathologic remission in the subgroup of patients with resectable esophageal cancer treated with induction chemotherapy and chemoradiation (with or without celecoxib).

To measure the radiographic response rate in patients with unresectable esophageal cancer.

Detailed description: This study is a two-part trial in which ten patients will receive a program of chemotherapy alone (for five weeks), followed by chemotherapy and radiation simultaneously (for five weeks), followed by surgical removal of the esophagus if this is possible. A second group of 15 patients will receive celecoxib (an anti-inflammatory medication) in addition to receiving the same treatment program as those patients in the first group.

Minimum age: 18 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Age 18 or older and able to provide informed consent

- Untreated, biopsy-proven squamous cell carcinoma or adenocarcinoma of the esophagus. Lesions including the gastroesophageal junction will be included provided the tumor involves less than 2cm of gastric cardia.

- Clinically staged II to IV disease who would receive chemoradiation either for preoperative or palliative indications.

- Clinical Status: ECOG performance status 0-2; life expectancy greater than 3 months; adequate nutrition; non-pregnant.

- Prior treatment: Greater than one week shall have elapsed since any major surgery.

- Laboratory requirements: WBC ≥ 4000/ul; Plt ≥ 100,000/ul; Serum creatinine < 1. 5 mg/dl; Bilirubin < 1. 5 mg/dl within two weeks of the start of therapy

- Informed consent: Patients must be told of the investigational nature of the study and must sign a written informed consent.

- Patients should be evaluated by a medical oncologist, radiation oncologist, and surgeon, and felt to be a suitable candidate for trimodality therapy.

- Patients who have had a prior malignancy are also eligible if they have been free of disease for 5 or more years.

Exclusion Criteria:

- No prior chemotherapy or radiotherapy is allowed.

- No treatment with a COX-2 inhibitor (selective or non-selective) within 30 days of the planned start of therapy.

- No serious medical or psychiatric illnesses which would prevent informed consent or otherwise limit survival to less than two years.

- History of refractory congestive heart failure or cardiomyopathy.

- No prior or concomitant malignancy is allowed other than curatively treated carcinoma in situ of the cervix, basal cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder.

- History of known NSAID-induced gastrointestinal bleeding or current history of peptic ulcer disease.

- Active coronary artery disease, history of MI within 3 months of treatment or history of CVA within 3 months of treatment.

- No concurrent use of seizure medications.

- No concurrent use of amifostine or other such agents.

- Patients with tracheoesophageal fistula found on bronchoscopy are excluded.

University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina 27599, United States

UNC Lineberger Comprehensive Cancer Center clinical trials page

Starting date: March 2005
Last updated: November 30, 2006