PET Scan Imaging in Assessing Response in Patients With Esophageal Cancer Receiving Combination Chemotherapy

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIBiomarker/Laboratory analysis, Diagnostic, Natural history/Epidemiology, TreatmentActive18 and overNCI, OtherCDR0000698428
CALGB-80803, NCT01333033

Trial Description

Summary

RATIONALE: PET scans done during chemotherapy may help doctors assess a patient's response to treatment and help plan the best treatment.

PURPOSE: This randomized phase II trial is studying PET scan imaging in assessing response in patients with esophageal cancer receiving combination chemotherapy.

Further Study Information

OBJECTIVES:

Primary

  • To induce a complete pathologic response (pCR) rate of 20% in positron emission tomography (PET) scan non-responders treated with either induction FOLFOX or carboplatin/paclitaxel, who then crossover to the other regimen during radiotherapy.

Secondary

  • To compare PET/CT response between induction treatment arms.
  • To compare pCR between induction treatment arms among PET/CT scan responders.
  • To directly compare pCR between induction treatment arms among non-responders if both treatment regimens are found to be efficacious.
  • To determine 8-month progression-free survival (PFS) in PET/CT scan responders, and in non-responders treated with alternative crossover chemoradiotherapy.
  • Estimate the PFS and overall survival (OS) curves, overall and among PET responders and PET/CT non-responders by induction treatment.
  • To determine the rate of postoperative anastomotic leak after neoadjuvant chemotherapy followed by chemoradiation.
  • To evaluate immunohistochemistry and RT-PCR of ERCC1, and genetic polymorphisms of ERCC1, XPD, and XRCC1.
  • To evaluate status and levels of methylation of nine candidate biomarker genes as well as expression levels of selected specific microRNAs, which will be correlated with chemoradiation response.
  • To compare the quality of life (QOL) of responders and nonresponders (as determined by PET/CT scanning) to presurgical treatment for esophageal cancer, in terms of global QOL, physical symptoms, physical functioning, and emotional well-being.
  • To examine the association between OS and QOL in esophageal cancer patients treated with chemotherapy, chemoradiation therapy, and surgery.

OUTLINE: This is a multicenter study. Patients are stratified according to T-stage (T1-2 vs T3-4) and nodal status (N0 vs N+). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive modified FOLFOX-6 therapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously on days 1-5. Treatment repeats every 14 days for 3 courses. Patients then undergo PET/CT scan. Patients with responsive disease (tumor metabolic activity decreased by ≥ 35%) receive 3 additional courses of FOLFOX-6 therapy and undergo concurrent radiotherapy (RT) (3D-conformal or intensity-modulated) once daily, 5 days a week, for approximately 6 weeks. Patients without responsive disease (tumor metabolic activity did not decrease by 35%) cross over to arm II during RT.
  • Arm II: Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 1 hour on days 1 and 8. Treatment repeats every 21 days for 2 courses. Patients then undergo PET/CT scan. Patients with responsive disease (tumor metabolic activity decreases ≥ 35%) continue to receive carboplatin IV over 30 minutes and paclitaxel IV over 1 hour once weekly for 5 weeks and undergo RT (3D-conformal or intensity-modulated) once a day, 5 days a week, for approximately 6 weeks. Patients without responsive disease (metabolic activity did not decrease by 35%) cross over to arm I during RT.

Within 4-10 weeks after completion of neoadjuvant chemoradiotherapy, patients undergo surgery at the discretion of the treating team.

Patients may undergo blood sample collection at baseline and periodically during study for correlative studies. Patients may also complete quality-of-life questionnaires at baseline and periodically during study.

After completion of study therapy, patients are followed up periodically for 5 years.

Eligibility Criteria

DISEASE CHARACTERISTICS:

  • Surgically resectable, histologically confirmed esophageal adenocarcinoma, including Siewert gastroesophageal (GE) junction adenocarcinomas Types 1 and 2
  • T1 N1-3 M0 or T2-4 N any M0 as determined by endoscopic ultrasound (EUS) and PET/CT (histologic confirmation of lymph involvement is not required)
  • All patients must have locoregional staging determined by EUS if technically feasible
  • All disease (tumor and nodes) must be both surgically resectable and capable of containment in a radiotherapy field
  • Endoscopy reports should clearly state both the T and N stage
  • No T4 tumor with clear evidence of invasion of the vertebral column, heart, great vessels, or tracheobronchial tree
  • No evidence of distant metastases (as determined by EUS or PET/CT)
  • Patients with cervical, supraclavicular, or other nodal disease that is either not included in the radiation field or is not able to be resected at the time of esophagectomy are not eligible
  • Patient must have pre-resection tissue available for central pathology review
  • Patients must have detectable fluorine-18-labeled deoxyglucose (FDG) uptake on baseline PET/CT scan of primary tumor

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • ANC ≥ 1,500/μL
  • Platelet count ≥ 100,000/μL
  • Hemoglobin ≥ 9 g/dL
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Creatinine clearance ≥ 60 mL/min
  • AST/ALT ≤ 2.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • No prior malignancy within 5 years, with the exception of basal or squamous cell skin cancers, or in situ bladder or cervical cancer
  • Patients with prior malignancy treated with surgery only and disease-free for more than 5 years are eligible
  • No history of severe hypersensitivity reaction to Cremaphor® EL
  • No known contraindication to the use of fluorouracil, taxanes, or platinum compounds

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior thoracic radiotherapy (RT), abdominal RT, or chemotherapy
  • No concurrent epoetin

Trial Contact Information

Trial Lead Organizations/Sponsors

Cancer and Leukemia Group B

  • National Cancer Institute
Karyn A. Goodman, MD, Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01333033
ClinicalTrials.gov processed this data on April 09, 2015

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.