Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by National Cancer Institute (NCI)
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01333033
First received: April 7, 2011
Last updated: February 15, 2013
Last verified: February 2013

April 7, 2011
February 15, 2013
September 2011
June 2017   (final data collection date for primary outcome measure)
pCR rate of PET/CT non-responders within each induction treatment group [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01333033 on ClinicalTrials.gov Archive Site
  • PET/CT response between treatment arms [ Designated as safety issue: No ]
  • pCR rate among induction treatment PET/CT scan responders [ Designated as safety issue: No ]
  • PFS and OS at 8 months [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
PET Scan Imaging in Assessing Response in Patients With Esophageal Cancer Receiving Combination Chemotherapy
Randomized Phase II Trial of PET Scan-Directed Combined Modality Therapy in Esophageal Cancer

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.

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.

Interventional
Phase 2
Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Cancer
  • Drug: FOLFOX regimen
    Given IV
  • Drug: carboplatin
    Given IV
  • Drug: fluorouracil
    Given IV
  • Drug: leucovorin calcium
    Given IV
  • Drug: oxaliplatin
    Given IV
  • Drug: paclitaxel
    Given IV
  • Experimental: 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.
    Interventions:
    • Drug: FOLFOX regimen
    • Drug: fluorouracil
    • Drug: leucovorin calcium
    • Drug: oxaliplatin
  • Experimental: 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.
    Interventions:
    • Drug: carboplatin
    • Drug: paclitaxel
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
204
Not Provided
June 2017   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
United States
 
NCT01333033
CDR0000698428, CALGB-80803
Not Provided
Monica M. Bertagnolli, Cancer and Leukemia Group B
Cancer and Leukemia Group B
National Cancer Institute (NCI)
Principal Investigator: Karyn A. Goodman, MD Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP