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

Esophageal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01333033
• Other study ID #: CALGB-80803
• Secondary ID: CDR0000698428NCI
• Status: Completed
• Phase: Phase 2
• Start date: July 2011
• Est. completion date: April 1, 2023

Study information

• Verified date: April 2023
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 257
• Est. completion date: April 1, 2023
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

• 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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Gastroesophageal Junction
• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Drug:
• Oxaliplatin
Given IV
• Leucovorin Calcium
Given IV
• Fluorouracil
Given IV
• Carboplatin
Given IV
• Paclitaxel
Given IV

Procedure:
• Positron Emission Tomography
Undergo PET/CT scan
• Computed Tomography
Undergo PET/CT scan

Radiation:
• Radiation Therapy
Undergo RT

Locations

Country	Name	City	State
United States	Kapiolani Medical Center at Pali Momi	'Aiea	Hawaii
United States	Oncare Hawaii, Incorporated - Pali Momi	'Aiea	Hawaii
United States	McFarland Clinic, PC	Ames	Iowa
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Mountainview Medical	Berlin	Vermont
United States	Billings Clinic - Downtown	Billings	Montana
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Center for Cancer Treatment & Prevention at Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	MeritCare Broadway	Fargo	North Dakota
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	OnCare Hawaii, Incorporated - Kuakini	Honolulu	Hawaii
United States	OnCare Hawaii, Incorporated - Lusitana	Honolulu	Hawaii
United States	Queen's Cancer Institute at Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital, Incorporated	Honolulu	Hawaii
United States	University of Mississippi Cancer Clinic	Jackson	Mississippi
United States	Castle Medical Center	Kailua	Hawaii
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	Kauai Medical Clinic	Lihue	Hawaii
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Saint Joseph's Hospital	Marshfield	Wisconsin
United States	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin
United States	Forbes Regional Hospital	Monroeville	Pennsylvania
United States	Camino Medical Group - Treatment Center	Mountain View	California
United States	Alle-Kiski Medical Center	Natrona Heights	Pennsylvania
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Yale Cancer Center	New Haven	Connecticut
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	Palo Alto Medical Foundation	Palo Alto	California
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	Fox Chase Cancer Center CCOP Research Base	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	UPMC Cancer Centers	Pittsburgh	Pennsylvania
United States	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Iredell Memorial Hospital	Statesville	North Carolina
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	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Pathological Response (pCR) of PET/CT Non-responders	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.	Up to 5 years
Secondary	PET/CT Response Between Treatment Arms	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).	Up to 5 years
Secondary	pCR Compared Between Induction Treatment Arms Among PET/CT Responders	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). 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.	Up to 5 years
Secondary	pCR Compared Among Non-responders Between Induction Treatment Arms if Treatment Regimens Are Found to be Efficacious	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.>; >>>; >; >>> Among the patients who completed induction therapy and did not respond, the percentage of patients reporting a pCR in each arm were compared.	Up to 5 years
Secondary	Progression Free Survival (PFS) Among PET/CT Non-responders Within Each Induction Treatment Group	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.	Up to 5 years