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Randomized Phase II Trial of PET Scan-Directed Combined Modality Therapy in Esophageal Cancer


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Adenocarcinoma of the Gastroesophageal Junction, Esophageal Cancer

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Trial Information

Randomized Phase II Trial of PET Scan-Directed Combined Modality Therapy in Esophageal Cancer


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

pCR rate of PET/CT non-responders within each induction treatment group

Safety Issue:

No

Principal Investigator

Karyn A. Goodman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

Unspecified

Study ID:

CDR0000698428

NCT ID:

NCT01333033

Start Date:

September 2011

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Cancer
  • 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
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Esophageal Diseases
  • Esophageal Neoplasms

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
University of Chicago Cancer Research CenterChicago, Illinois  60637
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
CCOP - Illinois Oncology Research AssociationPeoria, Illinois  61602
CCOP - Carle Cancer CenterUrbana, Illinois  61801
Siouxland Hematology-Oncology Associates, LLPSioux City, Iowa  51101
Saint Joseph Mercy Cancer CenterAnn Arbor, Michigan  48106-0995
Regions Hospital Cancer Care CenterSt. Paul, Minnesota  55101
United HospitalSt. Paul, Minnesota  55102
MeritCare BroadwayFargo, North Dakota  58122
CCOP - MeritCare HospitalFargo, North Dakota  58122
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
Marshfield Clinic - Indianhead CenterRice Lake, Wisconsin  54868
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
Kimmel Cancer Center at Thomas Jefferson University - PhiladelphiaPhiladelphia, Pennsylvania  19107
Fletcher Allen Health Care - University Health Center CampusBurlington, Vermont  05401
Blumenthal Cancer Center at Carolinas Medical CenterCharlotte, North Carolina  28232-2861
Yale Cancer CenterNew Haven, Connecticut  06520-8028
NYU Cancer Institute at New York University Medical CenterNew York, New York  10016
Mount Sinai Medical CenterNew York, New York  10029
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Presbyterian Cancer Center at Presbyterian HospitalCharlotte, North Carolina  28233-3549
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
Lombardi Comprehensive Cancer Center at Georgetown University Medical CenterWashington, District of Columbia  20007
University of Mississippi Cancer ClinicJackson, Mississippi  39216-4505
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Methodist Estabrook Cancer CenterOmaha, Nebraska  68114-4199
Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicago, Illinois  60611
UPMC Cancer CentersPittsburgh, Pennsylvania  15232
Oncology Hematology Associates of Central Illinois, PC - PeoriaPeoria, Illinois  61615
Cancer Institute of New Jersey at Cooper - VoorheesVoorhees, New Jersey  08043
Iredell Memorial HospitalStatesville, North Carolina  28677
Mountainview MedicalBerlin, Vermont  05602
Massachusetts General HospitalBoston, Massachusetts  02114-2617
Palo Alto Medical FoundationPalo Alto, California  94301
Regional Cancer Center at Singing River HospitalPascagoula, Mississippi  39581
Allegheny Cancer Center at Allegheny General HospitalPittsburgh, Pennsylvania  15212
Tunnell Cancer Center at Beebe Medical CenterLewes, Delaware  19958
McFarland Clinic, PCAmes, Iowa  50010
Billings Clinic - DowntownBillings, Montana  59107-7000
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer CenterColumbus, Ohio  43210-1240
Center for Cancer Treatment & Prevention at Sacred Heart HospitalEau Claire, Wisconsin  54701
Saint Joseph's HospitalMarshfield, Wisconsin  54449
Marshfield Clinic - Lakeland CenterMinocqua, Wisconsin  54548
Ministry Medical Group at Saint Mary's HospitalRhinelander, Wisconsin  54501
Marshfield Clinic at Saint Michael's HospitalStevens Point, Wisconsin  54481
Saint Michael's Hospital Cancer CenterStevens Point, Wisconsin  54481
Marshfield Clinic - Weston CenterWeston, Wisconsin  54476
Diagnostic and Treatment CenterWeston, Wisconsin  54476
Fox Chase Cancer Center CCOP Research BasePhiladelphia, Pennsylvania  19140
John H. Stroger, Jr. Hospital of Cook CountyChicago, Illinois  60612-9985
Queen's Cancer Institute at Queen's Medical CenterHonolulu, Hawaii  96813
Gibbs Regional Cancer Center at Spartanburg Regional Medical CenterSpartanburg, South Carolina  29303
Union Hospital of Cecil CountyElkton MD, Maryland  21921
Kapiolani Medical Center at Pali MomiAiea, Hawaii  96701
Kapiolani Medical Center for Women and ChildrenHonolulu, Hawaii  96826
Straub Clinic and Hospital, IncorporatedHonolulu, Hawaii  96813
OnCare Hawaii, Incorporated - KuakiniHonolulu, Hawaii  96817
OnCare Hawaii, Incorporated - LusitanaHonolulu, Hawaii  96813
Camino Medical Group - Treatment CenterMountain View, California  94040
Castle Medical CenterKailua, Hawaii  96734
Kauai Medical ClinicLihue, Hawaii  96766
Alle-Kiski Medical CenterNatrona Heights, Pennsylvania  15065
Kuakini Medical CenterHonolulu, Hawaii  96817
Forbes Regional HospitalMonroeville, Pennsylvania  15146
Oncare Hawaii, Incorporated - Pali MomiAiea, Hawaii  96701