Clinical trial NCT01333033: PET Scan Imaging in Assessing Response in Patients With Esophageal Cancer Receiving Combination Chemotherapy
Official title: Randomized Phase II Trial of PET Scan-Directed Combined Modality Therapy in Esophageal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adenocarcinoma of the Gastroesophageal Junction
Esophageal Cancer
Keywords: adenocarcinoma of the gastroesophageal junction
adenocarcinoma of the esophagus
stage IB esophageal cancer
stage IIA esophageal cancer
stage IIB esophageal cancer
stage IIIA esophageal cancer
stage IIIB esophageal cancer
stage IIIC esophageal cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2011-04-11
Enrollment: 257
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: * Surgically resectable, histologically confirmed esophageal adenocarcinoma, including Siewert gastroesophageal (GE) junction adenocarcinomas types 1 and 2
* T1N1-3M0 or T2-4NanyM0 as determined by endoscopic ultrasound (EUS) and PET/CT (histologic confirmation of lymph involvement is not required); all disease (tumor and nodes) must be both surgically resectable and capable of containment in a radiotherapy field; no T4 tumor with clear evidence of invasion of the vertebral column, heart, great vessels, or tracheobronchial tree
* All patients must have locoregional staging determined by endoscopic ultrasound (EUS) if technically feasible; endoscopy reports or subsequent gastrointestinal (GI) clinic note should clearly state both the T and N stage
* 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, in case that the patient has a pCR at the time of surgical resection to confirm diagnosis
* Patients must have an fludeoxyglucose F 18 (FDG)-avid tumor with a maximum standard uptake value (SUVmax) of \>= 5.0 on baseline PET/CT scan of primary tumor; baseline PET/CT scan should be performed; if it is necessary to repeat baseline PET/CT scan, reimbursement information is available
* No prior malignancy within 5 years of registration, 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; however, no prior thoracic radiation therapy (RT) or abdominal RT or chemotherapy allowed
* No known contraindication to the use of fluorouracil, taxanes, or platinum compounds
* No history of severe hypersensitivity reaction to Cremophor EL
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Patient must be non-pregnant and non-nursing; women of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 72 hours prior to randomization; women of child-bearing potential include any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea \>= 12 consecutive months; or women on hormone replacement therapy \[HRT\] with documented serum follicle stimulating hormone \[FSH\] level \> 35mIU/mL); even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential
* Absolute neutrophil count (ANC) \>= 1,500/μL
* Platelet count \>= 100,000/μL
* Bilirubin =\< 1.5 times upper limit of normal (ULN)
* Calculated creatinine clearance \>= 60 mL/min
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 times ULN

Primary outcomes:
measure: Complete Pathological Response (pCR) of PET/CT Non-responders
timeFrame: Up to 5 years
Secondary outcomes:
measure: PET/CT Response Between Treatment Arms
timeFrame: Up to 5 years
measure: pCR Compared Between Induction Treatment Arms Among PET/CT Responders
timeFrame: Up to 5 years
measure: pCR Compared Among Non-responders Between Induction Treatment Arms if Treatment Regimens Are Found to be Efficacious
timeFrame: Up to 5 years
measure: Progression Free Survival (PFS) Among PET/CT Non-responders Within Each Induction Treatment Group
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Mountain View
country: United States
facility: Camino Medical Group - Treatment Center
state: California
city: Palo Alto
country: United States
facility: Palo Alto Medical Foundation
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Lewes
country: United States
facility: Tunnell Cancer Center at Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
state: District of Columbia
city: 'Aiea
country: United States
facility: Kapiolani Medical Center at Pali Momi
state: Hawaii
city: 'Aiea
country: United States
facility: Oncare Hawaii, Incorporated - Pali Momi
state: Hawaii
city: Honolulu
country: United States
facility: OnCare Hawaii, Incorporated - Lusitana
state: Hawaii
city: Honolulu
country: United States
facility: Queen's Cancer Institute at Queen's Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: Straub Clinic and Hospital, Incorporated
state: Hawaii
city: Honolulu
country: United States
facility: OnCare Hawaii, Incorporated - Kuakini
state: Hawaii
city: Honolulu
country: United States
facility: Kuakini Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Kailua
country: United States
facility: Castle Medical Center
state: Hawaii
city: Lihue
country: United States
facility: Kauai Medical Clinic
state: Hawaii
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Chicago
country: United States
facility: John H. Stroger, Jr. Hospital of Cook County
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Peoria
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Peoria
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Ames
country: United States
facility: McFarland Clinic, PC
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Elkton
country: United States
facility: Union Hospital of Cecil County
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Cancer Center
state: Michigan
city: Saint Paul
country: United States
facility: Regions Hospital Cancer Care Center
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Cancer Clinic
state: Mississippi
city: Pascagoula
country: United States
facility: Regional Cancer Center at Singing River Hospital
state: Mississippi
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Omaha
country: United States
facility: Methodist Estabrook Cancer Center
state: Nebraska
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
state: New Jersey
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at Cooper - Voorhees
state: New Jersey
city: New York
country: United States
facility: NYU Cancer Institute at New York University Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Charlotte
country: United States
facility: Presbyterian Cancer Center at Presbyterian Hospital
state: North Carolina
city: Statesville
country: United States
facility: Iredell Memorial Hospital
state: North Carolina
city: Fargo
country: United States
facility: MeritCare Broadway
state: North Dakota
city: Fargo
country: United States
facility: CCOP - MeritCare Hospital
state: North Dakota
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Cancer Institute
state: Oklahoma
city: Monroeville
country: United States
facility: Forbes Regional Hospital
state: Pennsylvania
city: Natrona Heights
country: United States
facility: Alle-Kiski Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center CCOP Research Base
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Cancer Center at Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Centers
state: Pennsylvania
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Berlin
country: United States
facility: Mountainview Medical
state: Vermont
city: Burlington
country: United States
facility: Fletcher Allen Health Care - University Health Center Campus
state: Vermont
city: Eau Claire
country: United States
facility: Center for Cancer Treatment & Prevention at Sacred Heart Hospital
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic - Marshfield Center
state: Wisconsin
city: Marshfield
country: United States
facility: Saint Joseph's Hospital
state: Wisconsin
city: Minocqua
country: United States
facility: Marshfield Clinic - Lakeland Center
state: Wisconsin
city: Rhinelander
country: United States
facility: Ministry Medical Group at Saint Mary's Hospital
state: Wisconsin
city: Rice Lake
country: United States
facility: Marshfield Clinic - Indianhead Center
state: Wisconsin
city: Stevens Point
country: United States
facility: Marshfield Clinic at Saint Michael's Hospital
state: Wisconsin
city: Stevens Point
country: United States
facility: Saint Michael's Hospital Cancer Center
state: Wisconsin
city: Weston
country: United States
facility: Diagnostic and Treatment Center
state: Wisconsin
city: Weston
country: United States
facility: Marshfield Clinic - Weston Center
state: Wisconsin
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Karyn A. Goodman, MD
role: STUDY_CHAIR
References:
citation: Goodman KA, Ou FS, Hall NC, Bekaii-Saab T, Fruth B, Twohy E, Meyers MO, Boffa DJ, Mitchell K, Frankel WL, Niedzwiecki D, Noonan A, Janjigian YY, Thurmes PJ, Venook AP, Meyerhardt JA, O'Reilly EM, Ilson DH. Randomized Phase II Study of PET Response-Adapted Combined Modality Therapy for Esophageal Cancer: Mature Results of the CALGB 80803 (Alliance) Trial. J Clin Oncol. 2021 Sep 1;39(25):2803-2815. doi: 10.1200/JCO.20.03611. Epub 2021 Jun 2.
citation: Ku GY, Bains MS, Park DJ, Janjigian YY, Rusch VW, Rizk NP, Yoon SS, Millang B, Capanu M, Goodman KA, Ilson DH. Phase II study of bevacizumab and preoperative chemoradiation for esophageal adenocarcinoma. J Gastrointest Oncol. 2016 Dec;7(6):828-837. doi: 10.21037/jgo.2016.08.09.