Randomized Phase II Trial of PET Scan-Directed Combined Modality Therapy in Esophageal Cancer
- 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.
- 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
- 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.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
pCR rate of PET/CT non-responders within each induction treatment group
Karyn A. Goodman, MD
Memorial Sloan-Kettering Cancer Center
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|University of Chicago Cancer Research Center||Chicago, Illinois 60637|
|CCOP - Christiana Care Health Services||Wilmington, Delaware 19899|
|CCOP - Illinois Oncology Research Association||Peoria, Illinois 61602|
|CCOP - Carle Cancer Center||Urbana, Illinois 61801|
|Siouxland Hematology-Oncology Associates, LLP||Sioux City, Iowa 51101|
|Saint Joseph Mercy Cancer Center||Ann Arbor, Michigan 48106-0995|
|Regions Hospital Cancer Care Center||St. Paul, Minnesota 55101|
|United Hospital||St. Paul, Minnesota 55102|
|MeritCare Broadway||Fargo, North Dakota 58122|
|CCOP - MeritCare Hospital||Fargo, North Dakota 58122|
|Marshfield Clinic - Marshfield Center||Marshfield, Wisconsin 54449|
|Marshfield Clinic - Indianhead Center||Rice Lake, Wisconsin 54868|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill||Chapel Hill, North Carolina 27599-7570|
|Kimmel Cancer Center at Thomas Jefferson University - Philadelphia||Philadelphia, Pennsylvania 19107|
|Fletcher Allen Health Care - University Health Center Campus||Burlington, Vermont 05401|
|Blumenthal Cancer Center at Carolinas Medical Center||Charlotte, North Carolina 28232-2861|
|Yale Cancer Center||New Haven, Connecticut 06520-8028|
|NYU Cancer Institute at New York University Medical Center||New York, New York 10016|
|Mount Sinai Medical Center||New York, New York 10029|
|SUNY Upstate Medical University Hospital||Syracuse, New York 13210|
|Presbyterian Cancer Center at Presbyterian Hospital||Charlotte, North Carolina 28233-3549|
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|
|Lombardi Comprehensive Cancer Center at Georgetown University Medical Center||Washington, District of Columbia 20007|
|University of Mississippi Cancer Clinic||Jackson, Mississippi 39216-4505|
|Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis||St. Louis, Missouri 63110|
|Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School||New Brunswick, New Jersey 08903|
|Oklahoma University Cancer Institute||Oklahoma City, Oklahoma 73104|
|Methodist Estabrook Cancer Center||Omaha, Nebraska 68114-4199|
|Robert H. Lurie Comprehensive Cancer Center at Northwestern University||Chicago, Illinois 60611|
|UPMC Cancer Centers||Pittsburgh, Pennsylvania 15232|
|Oncology Hematology Associates of Central Illinois, PC - Peoria||Peoria, Illinois 61615|
|Cancer Institute of New Jersey at Cooper - Voorhees||Voorhees, New Jersey 08043|
|Iredell Memorial Hospital||Statesville, North Carolina 28677|
|Mountainview Medical||Berlin, Vermont 05602|
|Massachusetts General Hospital||Boston, Massachusetts 02114-2617|
|Palo Alto Medical Foundation||Palo Alto, California 94301|
|Regional Cancer Center at Singing River Hospital||Pascagoula, Mississippi 39581|
|Allegheny Cancer Center at Allegheny General Hospital||Pittsburgh, Pennsylvania 15212|
|Tunnell Cancer Center at Beebe Medical Center||Lewes, Delaware 19958|
|McFarland Clinic, PC||Ames, Iowa 50010|
|Billings Clinic - Downtown||Billings, Montana 59107-7000|
|Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center||Columbus, Ohio 43210-1240|
|Center for Cancer Treatment & Prevention at Sacred Heart Hospital||Eau Claire, Wisconsin 54701|
|Saint Joseph's Hospital||Marshfield, Wisconsin 54449|
|Marshfield Clinic - Lakeland Center||Minocqua, Wisconsin 54548|
|Ministry Medical Group at Saint Mary's Hospital||Rhinelander, Wisconsin 54501|
|Marshfield Clinic at Saint Michael's Hospital||Stevens Point, Wisconsin 54481|
|Saint Michael's Hospital Cancer Center||Stevens Point, Wisconsin 54481|
|Marshfield Clinic - Weston Center||Weston, Wisconsin 54476|
|Diagnostic and Treatment Center||Weston, Wisconsin 54476|
|Fox Chase Cancer Center CCOP Research Base||Philadelphia, Pennsylvania 19140|
|John H. Stroger, Jr. Hospital of Cook County||Chicago, Illinois 60612-9985|
|Queen's Cancer Institute at Queen's Medical Center||Honolulu, Hawaii 96813|
|Gibbs Regional Cancer Center at Spartanburg Regional Medical Center||Spartanburg, South Carolina 29303|
|Union Hospital of Cecil County||Elkton MD, Maryland 21921|
|Kapiolani Medical Center at Pali Momi||Aiea, Hawaii 96701|
|Kapiolani Medical Center for Women and Children||Honolulu, Hawaii 96826|
|Straub Clinic and Hospital, Incorporated||Honolulu, Hawaii 96813|
|OnCare Hawaii, Incorporated - Kuakini||Honolulu, Hawaii 96817|
|OnCare Hawaii, Incorporated - Lusitana||Honolulu, Hawaii 96813|
|Camino Medical Group - Treatment Center||Mountain View, California 94040|
|Castle Medical Center||Kailua, Hawaii 96734|
|Kauai Medical Clinic||Lihue, Hawaii 96766|
|Alle-Kiski Medical Center||Natrona Heights, Pennsylvania 15065|
|Kuakini Medical Center||Honolulu, Hawaii 96817|
|Forbes Regional Hospital||Monroeville, Pennsylvania 15146|
|Oncare Hawaii, Incorporated - Pali Momi||Aiea, Hawaii 96701|