PET Scan Imaging in Assessing Response in Patients With Esophageal Cancer Receiving Combination Chemotherapy
- Conditions
- Adenocarcinoma of the Gastroesophageal JunctionEsophageal Cancer
- Interventions
- Procedure: Positron Emission TomographyProcedure: Computed TomographyRadiation: Radiation Therapy
- Registration Number
- NCT01333033
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 257
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Arm I (FOLFOX regimen) Leucovorin Calcium 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 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 I (FOLFOX regimen) Positron Emission Tomography 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 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 I (FOLFOX regimen) Oxaliplatin 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 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 I (FOLFOX regimen) Radiation Therapy 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 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 I (FOLFOX regimen) Computed Tomography 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 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 (carboplatin + paclitaxel + radiation) Radiation Therapy 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 Arm I (FOLFOX regimen) Fluorouracil 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 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 I (FOLFOX regimen) Paclitaxel 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 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 I (FOLFOX regimen) Carboplatin 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 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 (carboplatin + paclitaxel + radiation) Carboplatin 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 Arm II (carboplatin + paclitaxel + radiation) Paclitaxel 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
- Primary Outcome Measures
Name Time Method Complete Pathological Response (pCR) of PET/CT Non-responders Up to 5 years The primary endpoint of this study is the percentage of PET/CT non-responders within each induction treatment group reporting a pCR. A pCR is defined as having no tumor found on pathology review at surgery in all resected lymph nodes and tissue. All tissues sampled must have NO viable tumor.
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) Among PET/CT Non-responders Within Each Induction Treatment Group Up to 5 years A non-responder was defined as having a PET/CT SUV (standard uptake value) decrease of less than 35% after induction.
Among the patients who completed induction therapy and did not respond, the progression free survival in each arm were compared. PFS will be measured from study entry until documented progression or death from any cause. PFS will be estimated using the method of Kaplan and Meier.PET/CT Response Between Treatment Arms Up to 5 years A PET/CT response to induction therapy is defined as metabolic activity of the tumor decreasing by \>=35%, as measured by maximum standardized uptake value (SUVmax).
pCR Compared Between Induction Treatment Arms Among PET/CT Responders Up to 5 years A PET/CT response to induction therapy is defined as metabolic activity of the tumor decreasing by \>=35%, as\>
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\>\> measured by maximum standardized uptake value (SUVmax). A pCR is defined as having no tumor found on pathology review at surgery in all resected lymph nodes and tissue. All tissues sampled must have NO viable tumor.pCR Compared Among Non-responders Between Induction Treatment Arms if Treatment Regimens Are Found to be Efficacious Up to 5 years A Complete Pathological Response (pCR) is defined as having no tumor found on pathology review at surgery in all resected lymph nodes and tissue. All tissues sampled must have NO viable tumor. A non-responder was defined as having a PET/CT SUV (standard uptake value) decrease of less than 35% after induction.\>
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\>\>\> Among the patients who completed induction therapy and did not respond, the percentage of patients reporting a pCR in each arm were compared.
Trial Locations
- Locations (68)
Diagnostic and Treatment Center
🇺🇸Weston, Wisconsin, United States
Fletcher Allen Health Care - University Health Center Campus
🇺🇸Burlington, Vermont, United States
Saint Joseph's Hospital
🇺🇸Marshfield, Wisconsin, United States
Marshfield Clinic - Weston Center
🇺🇸Weston, Wisconsin, United States
Queen's Cancer Institute at Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
OnCare Hawaii, Incorporated - Lusitana
🇺🇸Honolulu, Hawaii, United States
Kapiolani Medical Center for Women and Children
🇺🇸Honolulu, Hawaii, United States
Straub Clinic and Hospital, Incorporated
🇺🇸Honolulu, Hawaii, United States
OnCare Hawaii, Incorporated - Kuakini
🇺🇸Honolulu, Hawaii, United States
MeritCare Broadway
🇺🇸Fargo, North Dakota, United States
CCOP - MeritCare Hospital
🇺🇸Fargo, North Dakota, United States
Kauai Medical Clinic
🇺🇸Lihue, Hawaii, United States
Kapiolani Medical Center at Pali Momi
🇺🇸'Aiea, Hawaii, United States
Oncare Hawaii, Incorporated - Pali Momi
🇺🇸'Aiea, Hawaii, United States
Kuakini Medical Center
🇺🇸Honolulu, Hawaii, United States
Castle Medical Center
🇺🇸Kailua, Hawaii, United States
University of Mississippi Cancer Clinic
🇺🇸Jackson, Mississippi, United States
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Tunnell Cancer Center at Beebe Medical Center
🇺🇸Lewes, Delaware, United States
Billings Clinic - Downtown
🇺🇸Billings, Montana, United States
Palo Alto Medical Foundation
🇺🇸Palo Alto, California, United States
CCOP - Christiana Care Health Services
🇺🇸Newark, Delaware, United States
Regional Cancer Center at Singing River Hospital
🇺🇸Pascagoula, Mississippi, United States
Cancer Institute of New Jersey at Cooper - Voorhees
🇺🇸Voorhees, New Jersey, United States
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
🇺🇸Spartanburg, South Carolina, United States
Mountainview Medical
🇺🇸Berlin, Vermont, United States
Methodist Estabrook Cancer Center
🇺🇸Omaha, Nebraska, United States
Camino Medical Group - Treatment Center
🇺🇸Mountain View, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
🇺🇸Chicago, Illinois, United States
John H. Stroger, Jr. Hospital of Cook County
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Chicago Cancer Research Center
🇺🇸Chicago, Illinois, United States
CCOP - Illinois Oncology Research Association
🇺🇸Peoria, Illinois, United States
CCOP - Carle Cancer Center
🇺🇸Urbana, Illinois, United States
McFarland Clinic, PC
🇺🇸Ames, Iowa, United States
Union Hospital of Cecil County
🇺🇸Elkton, Maryland, United States
Oncology Hematology Associates of Central Illinois, PC - Peoria
🇺🇸Peoria, Illinois, United States
Siouxland Hematology-Oncology Associates, LLP
🇺🇸Sioux City, Iowa, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Regions Hospital Cancer Care Center
🇺🇸Saint Paul, Minnesota, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸Saint Louis, Missouri, United States
SUNY Upstate Medical University Hospital
🇺🇸Syracuse, New York, United States
NYU Cancer Institute at New York University Medical Center
🇺🇸New York, New York, United States
Presbyterian Cancer Center at Presbyterian Hospital
🇺🇸Charlotte, North Carolina, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Iredell Memorial Hospital
🇺🇸Statesville, North Carolina, United States
Blumenthal Cancer Center at Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Forbes Regional Hospital
🇺🇸Monroeville, Pennsylvania, United States
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Alle-Kiski Medical Center
🇺🇸Natrona Heights, Pennsylvania, United States
Fox Chase Cancer Center CCOP Research Base
🇺🇸Philadelphia, Pennsylvania, United States
Oklahoma University Cancer Institute
🇺🇸Oklahoma City, Oklahoma, United States
UPMC Cancer Centers
🇺🇸Pittsburgh, Pennsylvania, United States
Allegheny Cancer Center at Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Marshfield Clinic - Marshfield Center
🇺🇸Marshfield, Wisconsin, United States
Center for Cancer Treatment & Prevention at Sacred Heart Hospital
🇺🇸Eau Claire, Wisconsin, United States
Marshfield Clinic - Lakeland Center
🇺🇸Minocqua, Wisconsin, United States
Marshfield Clinic - Indianhead Center
🇺🇸Rice Lake, Wisconsin, United States
Marshfield Clinic at Saint Michael's Hospital
🇺🇸Stevens Point, Wisconsin, United States
Saint Michael's Hospital Cancer Center
🇺🇸Stevens Point, Wisconsin, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Saint Joseph Mercy Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Ministry Medical Group at Saint Mary's Hospital
🇺🇸Rhinelander, Wisconsin, United States