PET Scan Imaging in Assessing Response in Patients With Esophageal Cancer Receiving Combination Chemotherapy - Full Text View

Purpose

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.

Condition	Intervention	Phase
Adenocarcinoma of the Gastroesophageal Junction Esophageal Cancer	Drug: FOLFOX regimen Drug: carboplatin Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Drug: paclitaxel	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Open Label Primary Purpose: Treatment
Official Title:	Randomized Phase II Trial of PET Scan-Directed Combined Modality Therapy in Esophageal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Calcium Cancer Esophageal Cancer Esophagus Disorders Nuclear Scans

Drug Information available for: Fluorouracil Calcium Gluconate Leucovorin calcium Paclitaxel Carboplatin Oxaliplatin Levoleucovorin

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

pCR rate of PET/CT non-responders within each induction treatment group [ Designated as safety issue: No ]

Secondary Outcome Measures:

PET/CT response between treatment arms [ Designated as safety issue: No ]
pCR rate among induction treatment PET/CT scan responders [ Designated as safety issue: No ]
PFS and OS at 8 months [ Designated as safety issue: No ]

Estimated Enrollment:	204
Study Start Date:	September 2011
Estimated Primary Completion Date:	June 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 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.	Drug: FOLFOX regimen Given IV Drug: fluorouracil Given IV Drug: leucovorin calcium Given IV Drug: oxaliplatin Given IV
Experimental: 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.	Drug: carboplatin Given IV Drug: paclitaxel Given IV

Arms

Assigned Interventions

Experimental: 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.

Drug: FOLFOX regimen

Given IV

Drug: fluorouracil

Given IV

Drug: leucovorin calcium

Given IV

Drug: oxaliplatin

Given IV

Experimental: 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.

Drug: carboplatin

Given IV

Drug: paclitaxel

Given IV

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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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01333033

Show 68 Study Locations

Sponsors and Collaborators

Cancer and Leukemia Group B

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Karyn A. Goodman, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Monica M. Bertagnolli, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:	NCT01333033 History of Changes
Other Study ID Numbers:	CDR0000698428, CALGB-80803
Study First Received:	April 7, 2011
Last Updated:	February 15, 2013
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Adenocarcinoma
Adenocarcinoma, Mucinous
Esophageal Diseases
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
Gastrointestinal Diseases
Digestive System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms

Fluorouracil
Oxaliplatin
Carboplatin
Paclitaxel
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 17, 2013