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

NCT00520091 | Completed Phase 2 DMC

• 2 other identifiers: LCCC 0203CDR0000561610
• Study Type: interventional
• Target: 14
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Esophageal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Rates of cellular apoptosis and proliferation

  Measure the rates of cellular apoptotis and proliferation in esophageal cancers from biopsy samples pre-study and during chemoradiation with and without celecoxib therapy

  5 weeks

• Rate of pathologic complete remission in patients with resectable disease

  To determine if an acceptable rate of pathologic complete remissions can be achieved in a cohort of patients with potentially resectable esophageal carcinoma

  4 years

Secondary Outcomes (5)

• Number of subjects experiencing adverse events

  30 days post radiation

• Median overall survival of patients with resectable disease

  4 years

• Formation of prostaglandin E2 (PGE2) in tumor tissue

  12 weeks

• Downstream effects of inhibition of cyclooxygenase 2 function

  12 weeks

• Response Rate

  4 years

Study Arms (2)

Cohort 1

ACTIVE COMPARATOR

Induction chemotherapy and chemoradiation without celecoxib

Drug: CPT- 11; Drug: Cisplatin; Radiation: Radiation; Procedure: Surgery

Cohort 2

EXPERIMENTAL

Induction chemotherapy and chemoradiation with celecoxib

Drug: CPT- 11; Drug: Cisplatin; Drug: Celecoxib; Radiation: Radiation; Procedure: Surgery

Interventions

CPT- 11 DRUG

65mg/m2 given on days 1, 8 ,22 and 29 prior to surgery

Also known as: Irinotecan

Cohort 1; Cohort 2

Cisplatin DRUG

Cisplatin 30mg/m2 will be administered on days 1, 8, 22 and 29 prior to surgery

Also known as: Cis-diammine-dichloro-platinum

Cohort 1; Cohort 2

Celecoxib DRUG

400 mg, orally, twice per day beginning on day minus 3 and continue until the end of chemoradiation with CPT-11 and Cisplatin

Cohort 2

Radiation RADIATION

4,500 cGy in 180 cGy fractions 5 days per week, over a period of 5 weeks

Cohort 1; Cohort 2

Surgery PROCEDURE

Surgery will occur prior to chemoradiation therapy for those patients with resectable disease

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Esophageal Neoplasms; Adenocarcinoma Of Esophagus; Esophageal Squamous Cell Carcinoma

Interventions

Irinotecan; Cisplatin; Celecoxib; Radiation; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Physical Phenomena

Study Officials

• Bert H. O'Neil, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2007
• First Posted: August 23, 2007
• Study Start: March 1, 2005
• Primary Completion: November 1, 2006
• Study Completion: September 1, 2010
• Last Updated: May 18, 2012

Record last verified: 2012-05