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Esophageal CancerPhase 2NCT00520091

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

A Phase 2 study testing CPT- 11, Cisplatin and Celecoxib in people with Esophageal Cancer, run by UNC Lineberger Comprehensive Cancer Center.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Esophageal Cancer
What is being tested?
CPT- 11, Cisplatin and Celecoxib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
No sites listed yet
Study dates
Mar 2005to Sep 2010
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

About this study

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

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.

Read the 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.

Being tested
CPT- 11, Cisplatin, Celecoxib, Radiation, Surgery
Keywords
adenocarcinoma of the esophagus, squamous cell carcinoma of the esophagus, stage II esophageal cancer, stage III esophageal cancer, stage IV esophageal cancer
Medical subject headings
Esophageal Neoplasms, Adenocarcinoma Of Esophagus, Esophageal Squamous Cell Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CPT- 11Drug

    Also called Irinotecan

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

  • CisplatinDrug

    Also called Cis-diammine-dichloro-platinum

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

  • CelecoxibDrug

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

  • RadiationRadiation

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

  • SurgeryProcedure or surgery

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

Study groups in NCT00520091
Study groupRoleWhat they receive
Cohort 1Active comparatorInduction chemotherapy and chemoradiation without celecoxib
Receives: Drug: CPT- 11; Drug: Cisplatin; Radiation: Radiation; Procedure: Surgery
Cohort 2ExperimentalInduction chemotherapy and chemoradiation with celecoxib
Receives: Drug: CPT- 11; Drug: Cisplatin; Drug: Celecoxib; Radiation: Radiation; Procedure: Surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 5 weeks

  2. 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

    Measured: 4 years

Secondary outcomes (5)

  1. Number of subjects experiencing adverse events

    Adverse events/toxicity will graded per the CTCAE criteria

    Measured: 30 days post radiation

  2. Median overall survival of patients with resectable disease

    Follow up for survival will occur at 3 month intervals during the first two years, then every 6 months during years 3 and 4.

    Measured: 4 years

  3. Formation of prostaglandin E2 (PGE2) in tumor tissue

    The ability of celecoxib to decrease formation of prostaglandin E2 (PGE2) in tumor tissue will be analyzed using a Wilcoxon signed rank test on the difference (log scale) of the pre- and post-treatment tumor concentrations of PGE2

    Measured: 12 weeks

  4. Downstream effects of inhibition of cyclooxygenase 2 function

    A difference in location of the mRNA expression of the two cohorts will be tested for using the Wilcoxon rank sum test. A difference in the immunohistochemistry staining of the two cohorts will be tested for using polytomous logistic regression

    Measured: 12 weeks

  5. Response Rate

    Radiographic repsonse will be measured using RECIST critera in patients with unresectable esophageal cancer.

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Aug 2007 (estimated)
  2. Study startMar 2005
  3. Primary completionNov 2006
  4. Study completionSep 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00520091
Sponsor's protocol ID
LCCC 0203
Other IDs
CDR0000561610
Status last verified
May 2012
First submitted
21 Aug 2007
Last updated
18 May 2012
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CPT- 11, Cisplatin and Celecoxib in people with Esophageal Cancer, run by UNC Lineberger Comprehensive Cancer Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 May 2012. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rates of cellular apoptosis and proliferation (time frame: 5 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00520091.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2012.

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