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

Sponsor
Alliance for Clinical Trials in Oncology (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01333033
Collaborator
National Cancer Institute (NCI) (NIH)
257
68
2
3.8

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
257 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Randomized Phase II Trial of PET Scan-Directed Combined Modality Therapy in Esophageal Cancer
Actual Study Start Date :
Jul 1, 2011
Actual Primary Completion Date :
Nov 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm I (FOLFOX regimen)

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 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: Oxaliplatin
Given IV

Drug: Leucovorin Calcium
Given IV

Drug: Fluorouracil
Given IV

Drug: Carboplatin
Given IV

Drug: Paclitaxel
Given IV

Procedure: Positron Emission Tomography
Undergo PET/CT scan

Procedure: Computed Tomography
Undergo PET/CT scan

Radiation: Radiation Therapy
Undergo RT

Experimental: Arm II (carboplatin + paclitaxel + radiation)

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

Radiation: Radiation Therapy
Undergo RT

Outcome Measures

Primary Outcome Measures

  1. Complete Pathological Response (pCR) of PET/CT Non-responders [Up to 5 years]

    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.

Secondary Outcome Measures

  1. PET/CT Response Between Treatment Arms [Up to 5 years]

    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).

  2. pCR Compared Between Induction Treatment Arms Among PET/CT Responders [Up to 5 years]

    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.

  3. pCR Compared Among Non-responders Between Induction Treatment Arms if Treatment Regimens Are Found to be Efficacious [Up to 5 years]

    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.

  4. Progression Free Survival (PFS) Among PET/CT Non-responders Within Each Induction Treatment Group [Up to 5 years]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
  • 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Camino Medical Group - Treatment Center Mountain View California United States 94040
2 Palo Alto Medical Foundation Palo Alto California United States 94301
3 UCSF Helen Diller Family Comprehensive Cancer Center San Francisco California United States 94115
4 Yale Cancer Center New Haven Connecticut United States 06520-8028
5 Tunnell Cancer Center at Beebe Medical Center Lewes Delaware United States 19958
6 CCOP - Christiana Care Health Services Newark Delaware United States 19713
7 Lombardi Comprehensive Cancer Center at Georgetown University Medical Center Washington District of Columbia United States 20007
8 Kapiolani Medical Center at Pali Momi 'Aiea Hawaii United States 96701
9 Oncare Hawaii, Incorporated - Pali Momi 'Aiea Hawaii United States 96701
10 OnCare Hawaii, Incorporated - Lusitana Honolulu Hawaii United States 96813
11 Queen's Cancer Institute at Queen's Medical Center Honolulu Hawaii United States 96813
12 Straub Clinic and Hospital, Incorporated Honolulu Hawaii United States 96813
13 OnCare Hawaii, Incorporated - Kuakini Honolulu Hawaii United States 96817-3169
14 Kuakini Medical Center Honolulu Hawaii United States 96817
15 Kapiolani Medical Center for Women and Children Honolulu Hawaii United States 96826
16 Castle Medical Center Kailua Hawaii United States 96734
17 Kauai Medical Clinic Lihue Hawaii United States 96766
18 Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago Illinois United States 60611-3013
19 John H. Stroger, Jr. Hospital of Cook County Chicago Illinois United States 60612-3785
20 University of Chicago Cancer Research Center Chicago Illinois United States 60637-1470
21 CCOP - Illinois Oncology Research Association Peoria Illinois United States 61615
22 Oncology Hematology Associates of Central Illinois, PC - Peoria Peoria Illinois United States 61615
23 CCOP - Carle Cancer Center Urbana Illinois United States 61801
24 McFarland Clinic, PC Ames Iowa United States 50010
25 Siouxland Hematology-Oncology Associates, LLP Sioux City Iowa United States 51101
26 Union Hospital of Cecil County Elkton Maryland United States 21921
27 Massachusetts General Hospital Boston Massachusetts United States 02114
28 Saint Joseph Mercy Cancer Center Ann Arbor Michigan United States 48106-0995
29 Regions Hospital Cancer Care Center Saint Paul Minnesota United States 55101
30 United Hospital Saint Paul Minnesota United States 55102
31 University of Mississippi Cancer Clinic Jackson Mississippi United States 39216
32 Regional Cancer Center at Singing River Hospital Pascagoula Mississippi United States 39581
33 Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis Saint Louis Missouri United States 63110
34 Billings Clinic - Downtown Billings Montana United States 59107-7000
35 Methodist Estabrook Cancer Center Omaha Nebraska United States 68114
36 Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School New Brunswick New Jersey United States 08903
37 Cancer Institute of New Jersey at Cooper - Voorhees Voorhees New Jersey United States 08043
38 NYU Cancer Institute at New York University Medical Center New York New York United States 10016
39 Mount Sinai Medical Center New York New York United States 10029
40 Memorial Sloan-Kettering Cancer Center New York New York United States 10065
41 SUNY Upstate Medical University Hospital Syracuse New York United States 13210
42 Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Chapel Hill North Carolina United States 27599-7295
43 Blumenthal Cancer Center at Carolinas Medical Center Charlotte North Carolina United States 28232-2861
44 Presbyterian Cancer Center at Presbyterian Hospital Charlotte North Carolina United States 28233-3549
45 Iredell Memorial Hospital Statesville North Carolina United States 28677
46 MeritCare Broadway Fargo North Dakota United States 58102
47 CCOP - MeritCare Hospital Fargo North Dakota United States 58122
48 Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43210-1240
49 Oklahoma University Cancer Institute Oklahoma City Oklahoma United States 73104
50 Forbes Regional Hospital Monroeville Pennsylvania United States 15146
51 Alle-Kiski Medical Center Natrona Heights Pennsylvania United States 15065
52 Kimmel Cancer Center at Thomas Jefferson University - Philadelphia Philadelphia Pennsylvania United States 19107-5541
53 Fox Chase Cancer Center CCOP Research Base Philadelphia Pennsylvania United States 19140
54 Allegheny Cancer Center at Allegheny General Hospital Pittsburgh Pennsylvania United States 15212
55 UPMC Cancer Centers Pittsburgh Pennsylvania United States 15232
56 Gibbs Regional Cancer Center at Spartanburg Regional Medical Center Spartanburg South Carolina United States 29303
57 Mountainview Medical Berlin Vermont United States 05602
58 Fletcher Allen Health Care - University Health Center Campus Burlington Vermont United States 05401
59 Center for Cancer Treatment & Prevention at Sacred Heart Hospital Eau Claire Wisconsin United States 54701
60 Marshfield Clinic - Marshfield Center Marshfield Wisconsin United States 54449
61 Saint Joseph's Hospital Marshfield Wisconsin United States 54449
62 Marshfield Clinic - Lakeland Center Minocqua Wisconsin United States 54548
63 Ministry Medical Group at Saint Mary's Hospital Rhinelander Wisconsin United States 54501
64 Marshfield Clinic - Indianhead Center Rice Lake Wisconsin United States 54868
65 Marshfield Clinic at Saint Michael's Hospital Stevens Point Wisconsin United States 54481
66 Saint Michael's Hospital Cancer Center Stevens Point Wisconsin United States 54481
67 Diagnostic and Treatment Center Weston Wisconsin United States 54476
68 Marshfield Clinic - Weston Center Weston Wisconsin United States 54476

Sponsors and Collaborators

  • Alliance for Clinical Trials in Oncology
  • National Cancer Institute (NCI)

Investigators

  • Study Chair: Karyn A. Goodman, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01333033
Other Study ID Numbers:
  • CALGB-80803
  • CDR0000698428
  • NCI-2011-02642
  • U10CA180821
First Posted:
Apr 11, 2011
Last Update Posted:
Nov 3, 2021
Last Verified:
Oct 1, 2021

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title FOLFOX Responder FOLFOX Non-Responder CP Responder CP Non-Responder CP No Cross-over FOLFOX6 No Cross-over
Arm/Group Description 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 RT (3D-conformal or intensity-modulated) once daily, 5 days a week, for approximately 6 weeks. 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 without responsive disease (tumor metabolic activity did not decrease by 35%) cross over to Arm II during RT.n Emission Tomography: Undergo PET/CT scan 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 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 without responsive disease (metabolic activity did not decrease by 35%) cross over to Arm I during RT Carboplatin/ Paclitaxel days 1,8,22,29 modified FOLFOX6 days 1,15, 29
Period Title: Overall Study
STARTED 72 39 64 50 14 18
COMPLETED 72 39 64 50 0 0
NOT COMPLETED 0 0 0 0 14 18

Baseline Characteristics

Arm/Group Title Arm I (FOLFOX Regimen) Arm II (Carboplatin + Paclitaxel + Radiation) Total
Arm/Group Description 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 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. Oxaliplatin: Given IV Leucovorin Calcium: Given IV Fluorouracil: Given IV Carboplatin: Given IV Paclitaxel: Given IV Positron Emission Tomography: Undergo PET/CT scan Computed Tomography: Undergo PET/CT scan Radiation Therapy: Undergo RT 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 Carboplatin: Given IV Paclitaxel: Given IV Radiation Therapy: Undergo RT Total of all reporting groups
Overall Participants 129 128 257
Age (years) [Median (Full Range) ]
Median (Full Range) [years]
62
64
64
Sex: Female, Male (Count of Participants)
Female
16
12.4%
14
10.9%
30
11.7%
Male
113
87.6%
114
89.1%
227
88.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
1
0.8%
3
2.3%
4
1.6%
Not Hispanic or Latino
126
97.7%
124
96.9%
250
97.3%
Unknown or Not Reported
2
1.6%
1
0.8%
3
1.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
2
1.6%
2
0.8%
Asian
3
2.3%
3
2.3%
6
2.3%
Native Hawaiian or Other Pacific Islander
0
0%
1
0.8%
1
0.4%
Black or African American
6
4.7%
4
3.1%
10
3.9%
White
119
92.2%
116
90.6%
235
91.4%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
1
0.8%
2
1.6%
3
1.2%
Region of Enrollment (participants) [Number]
United States
129
100%
128
100%
257
100%

Outcome Measures

1. Primary Outcome
Title Complete Pathological Response (pCR) of PET/CT Non-responders
Description 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.
Time Frame Up to 5 years

Outcome Measure Data

Analysis Population Description
All eligible patients that registered to treatment and reported no PET/CT response to induction treatment were included in this endpoint.
Arm/Group Title FOLFOX Non-Responder CP Non-Responder
Arm/Group Description 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 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.> >>> > >>> Oxaliplatin: Given IV> >>> > >>> Leucovorin Calcium: Given IV> >>> > >>> Fluorouracil: Given IV> >>> > >>> Carboplatin: Given IV> >>> > >>> Paclitaxel: Given IV> >>> > >>> Positron Emission Tomography: Undergo PET/CT scan> >>> > >>> Computed Tomography: Undergo PET/CT scan> >>> > >>> Radiation Therapy: Undergo RT 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> >>> > >>> Carboplatin: Given IV> >>> > >>> Paclitaxel: Given IV> >>> > >>> Radiation Therapy: Undergo RT
Measure Participants 39 50
Number (95% Confidence Interval) [percentage of participants with a pCR]
17.95
13.9%
20
15.6%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FOLFOX Non-Responder, CP Non-Responder
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 1.0
Comments
Method Fisher Exact
Comments
2. Secondary Outcome
Title PET/CT Response Between Treatment Arms
Description 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).
Time Frame Up to 5 years

Outcome Measure Data

Analysis Population Description
All participants that were assessed for an induction response are included in this analysis.
Arm/Group Title FOLFOX Regimen CP (Carboplatin + Paclitaxel + Radiation)
Arm/Group Description 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 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.> >> >> >> > >> >> >> Oxaliplatin: Given IV> >> >> >> > >> >> >> Leucovorin Calcium: Given IV> >> >> >> > >> >> >> Fluorouracil: Given IV> >> >> >> > >> >> >> Carboplatin: Given IV> >> >> >> > >> >> >> Paclitaxel: Given IV> >> >> >> > >> >> >> Positron Emission Tomography: Undergo PET/CT scan> >> >> >> > >> >> >> Computed Tomography: Undergo PET/CT scan> >> >> >> > >> >> >> Radiation Therapy: Undergo RT 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> >> >> >> > >> >> >> Carboplatin: Given IV> >> >> >> > >> >> >> Paclitaxel: Given IV> >> >> >> > >> >> >> Radiation Therapy: Undergo RT
Measure Participants 111 114
Number (95% Confidence Interval) [percentage of patients with a response]
64.86
56.14
3. Secondary Outcome
Title pCR Compared Between Induction Treatment Arms Among PET/CT Responders
Description 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.
Time Frame Up to 5 years

Outcome Measure Data

Analysis Population Description
All eligible patients that were assessed as a PET responder by induction were included in this analysis.
Arm/Group Title FOLFOX Responder CP (Carboplatin + Paclitaxel + Radiation) Responder
Arm/Group Description 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 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.> >> >> >> > >> >> >> Oxaliplatin: Given IV> >> >> >> > >> >> >> Leucovorin Calcium: Given IV> >> >> >> > >> >> >> Fluorouracil: Given IV> >> >> >> > >> >> >> Carboplatin: Given IV> >> >> >> > >> >> >> Paclitaxel: Given IV> >> >> >> > >> >> >> Positron Emission Tomography: Undergo PET/CT scan> >> >> >> > >> >> >> Computed Tomography: Undergo PET/CT scan> >> >> >> > >> >> >> Radiation Therapy: Undergo RT 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> >> >> >> > >> >> >> Carboplatin: Given IV> >> >> >> > >> >> >> Paclitaxel: Given IV> >> >> >> > >> >> >> Radiation Therapy: Undergo RT
Measure Participants 72 64
Number (95% Confidence Interval) [percentage of participants with a pCR]
40.28
31.2%
14.06
11%
4. Secondary Outcome
Title pCR Compared Among Non-responders Between Induction Treatment Arms if Treatment Regimens Are Found to be Efficacious
Description 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.
Time Frame Up to 5 years

Outcome Measure Data

Analysis Population Description
All patients who completed induction therapy and were classified as a non-responder were included in this analysis.
Arm/Group Title FOLFOX Regimen Non-Responders CP (Carboplatin + Paclitaxel + Radiation) Non-Responders
Arm/Group Description 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 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.> >>> > >>> Oxaliplatin: Given IV> >>> > >>> Leucovorin Calcium: Given IV> >>> > >>> Fluorouracil: Given IV> >>> > >>> Carboplatin: Given IV> >>> > >>> Paclitaxel: Given IV> >>> > >>> Positron Emission Tomography: Undergo PET/CT scan> >>> > >>> Computed Tomography: Undergo PET/CT scan> >>> > >>> Radiation Therapy: Undergo RT 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> >>> > >>> Carboplatin: Given IV> >>> > >>> Paclitaxel: Given IV> >>> > >>> Radiation Therapy: Undergo RT
Measure Participants 39 50
Number (95% Confidence Interval) [percentage of participants with a pCR]
17.95
13.9%
20
15.6%
5. Secondary Outcome
Title Progression Free Survival (PFS) Among PET/CT Non-responders Within Each Induction Treatment Group
Description 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.
Time Frame Up to 5 years

Outcome Measure Data

Analysis Population Description
All patients that began induction therapy and did not report a response were included in this analysis.
Arm/Group Title FOLFOX Regimen Non-Responder CP Non-Responder
Arm/Group Description 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 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. > >> > > >> > Oxaliplatin: Given IV > >> > > >> > Leucovorin Calcium: Given IV > >> > > >> > Fluorouracil: Given IV > >> > > >> > Carboplatin: Given IV > >> > > >> > Paclitaxel: Given IV > >> > > >> > Positron Emission Tomography: Undergo PET/CT scan > >> > > >> > Computed Tomography: Undergo PET/CT scan > >> > > >> > Radiation Therapy: Undergo RT 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 without responsive disease (metabolic activity did not decrease by 35%) cross over to Arm I during RT
Measure Participants 39 50
Median (95% Confidence Interval) [months]
NA
33.4

Adverse Events

Time Frame 5 years
Adverse Event Reporting Description
Arm/Group Title FOLFOX Responder FOLFOX Non-Responder CP Responder CP Non-Responder CP No Cross-over FOLFOX No Cross-over
Arm/Group Description 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 RT (3D-conformal or intensity-modulated) once daily, 5 days a week, for approximately 6 weeks. 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 without responsive disease (tumor metabolic activity did not decrease by 35%) cross over to Arm II during RT.n Emission Tomography: Undergo PET/CT scan 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 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 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 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.
All Cause Mortality
FOLFOX Responder FOLFOX Non-Responder CP Responder CP Non-Responder CP No Cross-over FOLFOX No Cross-over
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 3/72 (4.2%) 1/39 (2.6%) 2/64 (3.1%) 4/49 (8.2%) 0/9 (0%) 0/5 (0%)
Serious Adverse Events
FOLFOX Responder FOLFOX Non-Responder CP Responder CP Non-Responder CP No Cross-over FOLFOX No Cross-over
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 3/72 (4.2%) 1/39 (2.6%) 2/64 (3.1%) 4/49 (8.2%) 0/9 (0%) 0/5 (0%)
Cardiac disorders
Cardiac arrest 0/72 (0%) 0 1/39 (2.6%) 1 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Gastrointestinal disorders
Esophageal perforation 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Injury, poisoning and procedural complications
Esophageal anastomotic leak 0/72 (0%) 0 0/39 (0%) 0 1/64 (1.6%) 1 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Dyspnea 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Respiratory failure 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Vascular disorders
Thromboembolic event 0/72 (0%) 0 0/39 (0%) 0 1/64 (1.6%) 1 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Other (Not Including Serious) Adverse Events
FOLFOX Responder FOLFOX Non-Responder CP Responder CP Non-Responder CP No Cross-over FOLFOX No Cross-over
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 72/72 (100%) 38/39 (97.4%) 63/64 (98.4%) 46/49 (93.9%) 9/9 (100%) 4/5 (80%)
Blood and lymphatic system disorders
Anemia 6/72 (8.3%) 19 7/39 (17.9%) 11 5/64 (7.8%) 9 10/49 (20.4%) 15 0/9 (0%) 0 0/5 (0%) 0
Blood and lymph sys disorders - Oth Spec 1/72 (1.4%) 1 1/39 (2.6%) 1 2/64 (3.1%) 6 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Febrile neutropenia 0/72 (0%) 0 2/39 (5.1%) 2 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Leukocytosis 2/72 (2.8%) 4 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Thrombotic thrombocytopenic purpura 3/72 (4.2%) 13 1/39 (2.6%) 5 3/64 (4.7%) 4 2/49 (4.1%) 3 0/9 (0%) 0 0/5 (0%) 0
Cardiac disorders
Acute coronary syndrome 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 2 0/9 (0%) 0 0/5 (0%) 0
Atrial fibrillation 1/72 (1.4%) 1 0/39 (0%) 0 1/64 (1.6%) 2 4/49 (8.2%) 5 0/9 (0%) 0 0/5 (0%) 0
Atrioventricular block complete 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Cardiac arrest 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 1/5 (20%) 1
Heart failure 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Myocardial infarction 1/72 (1.4%) 2 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Palpitations 0/72 (0%) 0 1/39 (2.6%) 1 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Pericardial effusion 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 2 0/9 (0%) 0 0/5 (0%) 0
Pericarditis 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Sinus bradycardia 1/72 (1.4%) 1 1/39 (2.6%) 4 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 2/5 (40%) 2
Sinus tachycardia 1/72 (1.4%) 1 2/39 (5.1%) 2 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Ventricular tachycardia 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Ear and labyrinth disorders
Hearing impaired 0/72 (0%) 0 0/39 (0%) 0 1/64 (1.6%) 3 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Endocrine disorders
Endocrine disorders - Other, specify 0/72 (0%) 0 0/39 (0%) 0 1/64 (1.6%) 3 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Eye disorders
Blurred vision 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Cataract 0/72 (0%) 0 0/39 (0%) 0 1/64 (1.6%) 3 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Gastrointestinal disorders
Abdominal pain 1/72 (1.4%) 1 0/39 (0%) 0 1/64 (1.6%) 1 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Ascites 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Bloating 0/72 (0%) 0 2/39 (5.1%) 2 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Constipation 6/72 (8.3%) 15 2/39 (5.1%) 2 3/64 (4.7%) 5 2/49 (4.1%) 2 0/9 (0%) 0 0/5 (0%) 0
Diarrhea 36/72 (50%) 87 16/39 (41%) 24 23/64 (35.9%) 39 20/49 (40.8%) 42 1/9 (11.1%) 2 1/5 (20%) 1
Dry mouth 1/72 (1.4%) 3 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Dyspepsia 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Dysphagia 10/72 (13.9%) 36 11/39 (28.2%) 28 7/64 (10.9%) 10 8/49 (16.3%) 19 1/9 (11.1%) 2 0/5 (0%) 0
Esophageal fistula 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Esophageal hemorrhage 1/72 (1.4%) 1 1/39 (2.6%) 1 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Esophageal obstruction 1/72 (1.4%) 2 1/39 (2.6%) 1 1/64 (1.6%) 3 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Esophageal pain 1/72 (1.4%) 1 3/39 (7.7%) 4 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Esophageal stenosis 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 2 0/9 (0%) 0 0/5 (0%) 0
Esophagitis 6/72 (8.3%) 11 3/39 (7.7%) 3 2/64 (3.1%) 2 1/49 (2%) 2 0/9 (0%) 0 0/5 (0%) 0
Gastric hemorrhage 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Gastric ulcer 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Gastritis 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Gastroesophageal reflux disease 2/72 (2.8%) 6 0/39 (0%) 0 1/64 (1.6%) 2 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Gastrointestinal disorders - Oth spec 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Gastroparesis 1/72 (1.4%) 3 1/39 (2.6%) 2 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Ileus 0/72 (0%) 0 0/39 (0%) 0 1/64 (1.6%) 1 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Jejunal fistula 0/72 (0%) 0 0/39 (0%) 0 1/64 (1.6%) 1 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Malabsorption 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 2/49 (4.1%) 6 0/9 (0%) 0 0/5 (0%) 0
Mucositis oral 4/72 (5.6%) 4 0/39 (0%) 0 0/64 (0%) 0 2/49 (4.1%) 2 0/9 (0%) 0 0/5 (0%) 0
Nausea 56/72 (77.8%) 192 31/39 (79.5%) 88 42/64 (65.6%) 89 38/49 (77.6%) 120 6/9 (66.7%) 9 0/5 (0%) 0
Obstruction gastric 0/72 (0%) 0 0/39 (0%) 0 1/64 (1.6%) 1 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Stomach pain 0/72 (0%) 0 1/39 (2.6%) 1 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Upper gastrointestinal hemorrhage 0/72 (0%) 0 0/39 (0%) 0 1/64 (1.6%) 1 0/49 (0%) 0 1/9 (11.1%) 1 0/5 (0%) 0
Vomiting 33/72 (45.8%) 66 18/39 (46.2%) 37 18/64 (28.1%) 29 20/49 (40.8%) 46 3/9 (33.3%) 5 1/5 (20%) 1
General disorders
Chills 1/72 (1.4%) 1 3/39 (7.7%) 3 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Edema limbs 1/72 (1.4%) 1 1/39 (2.6%) 4 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Fatigue 15/72 (20.8%) 39 9/39 (23.1%) 22 4/64 (6.3%) 4 6/49 (12.2%) 12 0/9 (0%) 0 0/5 (0%) 0
Fever 11/72 (15.3%) 16 4/39 (10.3%) 5 10/64 (15.6%) 15 8/49 (16.3%) 9 0/9 (0%) 0 0/5 (0%) 0
Flu like symptoms 4/72 (5.6%) 14 4/39 (10.3%) 4 3/64 (4.7%) 5 2/49 (4.1%) 3 0/9 (0%) 0 0/5 (0%) 0
Gen disord and admin site conds-Oth spec 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Non-cardiac chest pain 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 2 0/9 (0%) 0 1/5 (20%) 1
Pain 3/72 (4.2%) 4 2/39 (5.1%) 4 3/64 (4.7%) 4 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Hepatobiliary disorders
Bile duct stenosis 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Cholecystitis 0/72 (0%) 0 0/39 (0%) 0 1/64 (1.6%) 1 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Hepatobiliary disorders - Other, specify 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Immune system disorders
Anaphylaxis 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 1/5 (20%) 1
Infections and infestations
Catheter related infection 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Device related infection 1/72 (1.4%) 2 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Infections and infestations - Oth spec 1/72 (1.4%) 2 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Lung infection 1/72 (1.4%) 1 1/39 (2.6%) 1 0/64 (0%) 0 2/49 (4.1%) 2 0/9 (0%) 0 0/5 (0%) 0
Sepsis 0/72 (0%) 0 1/39 (2.6%) 1 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Skin infection 0/72 (0%) 0 0/39 (0%) 0 1/64 (1.6%) 1 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Soft tissue infection 0/72 (0%) 0 1/39 (2.6%) 1 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Tooth infection 0/72 (0%) 0 1/39 (2.6%) 1 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Urinary tract infection 0/72 (0%) 0 0/39 (0%) 0 1/64 (1.6%) 1 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Wound infection 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 2/49 (4.1%) 3 0/9 (0%) 0 0/5 (0%) 0
Injury, poisoning and procedural complications
Esophageal anastomotic leak 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Gastrointestinal stoma necrosis 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Infusion related reaction 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 2/5 (40%) 2
Investigations
Alanine aminotransferase increased 3/72 (4.2%) 6 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Alkaline phosphatase increased 0/72 (0%) 0 1/39 (2.6%) 2 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Aspartate aminotransferase increased 4/72 (5.6%) 9 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Blood bilirubin increased 2/72 (2.8%) 2 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
CD4 lymphocytes decreased 1/72 (1.4%) 3 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Ejection fraction decreased 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 2 0/9 (0%) 0 0/5 (0%) 0
INR increased 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Lymphocyte count decreased 26/72 (36.1%) 66 15/39 (38.5%) 23 27/64 (42.2%) 37 19/49 (38.8%) 53 0/9 (0%) 0 1/5 (20%) 1
Lymphocyte count increased 0/72 (0%) 0 0/39 (0%) 0 1/64 (1.6%) 1 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Neutrophil count decreased 24/72 (33.3%) 46 18/39 (46.2%) 24 30/64 (46.9%) 50 15/49 (30.6%) 37 4/9 (44.4%) 4 0/5 (0%) 0
Platelet count decreased 44/72 (61.1%) 145 25/39 (64.1%) 52 44/64 (68.8%) 69 25/49 (51%) 71 2/9 (22.2%) 2 1/5 (20%) 1
Weight loss 4/72 (5.6%) 9 3/39 (7.7%) 3 0/64 (0%) 0 3/49 (6.1%) 5 1/9 (11.1%) 1 0/5 (0%) 0
White blood cell decreased 2/72 (2.8%) 4 8/39 (20.5%) 8 14/64 (21.9%) 16 1/49 (2%) 5 0/9 (0%) 0 0/5 (0%) 0
Metabolism and nutrition disorders
Anorexia 7/72 (9.7%) 15 6/39 (15.4%) 7 2/64 (3.1%) 2 4/49 (8.2%) 5 1/9 (11.1%) 1 0/5 (0%) 0
Dehydration 3/72 (4.2%) 4 5/39 (12.8%) 7 3/64 (4.7%) 3 5/49 (10.2%) 5 0/9 (0%) 0 0/5 (0%) 0
Hyperglycemia 4/72 (5.6%) 10 3/39 (7.7%) 3 4/64 (6.3%) 7 2/49 (4.1%) 11 0/9 (0%) 0 0/5 (0%) 0
Hyperkalemia 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Hypoalbuminemia 3/72 (4.2%) 5 2/39 (5.1%) 5 1/64 (1.6%) 1 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Hypocalcemia 2/72 (2.8%) 2 3/39 (7.7%) 6 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Hypoglycemia 2/72 (2.8%) 3 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Hypokalemia 3/72 (4.2%) 3 2/39 (5.1%) 2 1/64 (1.6%) 1 5/49 (10.2%) 7 0/9 (0%) 0 0/5 (0%) 0
Hyponatremia 0/72 (0%) 0 4/39 (10.3%) 4 3/64 (4.7%) 4 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Hypophosphatemia 0/72 (0%) 0 1/39 (2.6%) 1 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Musculoskeletal and connective tissue disorders
Arthralgia 6/72 (8.3%) 16 3/39 (7.7%) 5 13/64 (20.3%) 25 5/49 (10.2%) 14 0/9 (0%) 0 1/5 (20%) 1
Back pain 1/72 (1.4%) 1 1/39 (2.6%) 1 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Generalized muscle weakness 3/72 (4.2%) 4 0/39 (0%) 0 2/64 (3.1%) 2 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Myalgia 6/72 (8.3%) 18 4/39 (10.3%) 7 11/64 (17.2%) 15 4/49 (8.2%) 6 0/9 (0%) 0 0/5 (0%) 0
Pain in extremity 0/72 (0%) 0 1/39 (2.6%) 3 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, mal, uncpec - Oth spec 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Nervous system disorders
Dizziness 3/72 (4.2%) 5 0/39 (0%) 0 1/64 (1.6%) 1 2/49 (4.1%) 5 0/9 (0%) 0 0/5 (0%) 0
Dysgeusia 2/72 (2.8%) 6 1/39 (2.6%) 1 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Headache 12/72 (16.7%) 27 6/39 (15.4%) 7 15/64 (23.4%) 26 3/49 (6.1%) 8 0/9 (0%) 0 1/5 (20%) 1
Paresthesia 32/72 (44.4%) 120 16/39 (41%) 35 11/64 (17.2%) 30 12/49 (24.5%) 34 0/9 (0%) 0 0/5 (0%) 0
Peripheral motor neuropathy 18/72 (25%) 37 5/39 (12.8%) 11 14/64 (21.9%) 21 4/49 (8.2%) 12 3/9 (33.3%) 7 0/5 (0%) 0
Peripheral sensory neuropathy 2/72 (2.8%) 6 2/39 (5.1%) 2 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Presyncope 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Syncope 2/72 (2.8%) 2 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Psychiatric disorders
Confusion 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Delirium 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 2 0/9 (0%) 0 0/5 (0%) 0
Depression 0/72 (0%) 0 1/39 (2.6%) 1 1/64 (1.6%) 1 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Insomnia 1/72 (1.4%) 2 3/39 (7.7%) 3 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Renal and urinary disorders
Acute kidney injury 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 2/49 (4.1%) 2 0/9 (0%) 0 0/5 (0%) 0
Urinary frequency 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Urinary retention 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 1/9 (11.1%) 1 0/5 (0%) 0
Respiratory, thoracic and mediastinal disorders
Apnea 0/72 (0%) 0 0/39 (0%) 0 1/64 (1.6%) 3 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Aspiration 0/72 (0%) 0 2/39 (5.1%) 2 1/64 (1.6%) 1 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Atelectasis 0/72 (0%) 0 1/39 (2.6%) 1 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Chylothorax 0/72 (0%) 0 0/39 (0%) 0 1/64 (1.6%) 1 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Cough 2/72 (2.8%) 5 1/39 (2.6%) 1 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Dyspnea 12/72 (16.7%) 36 10/39 (25.6%) 15 17/64 (26.6%) 30 21/49 (42.9%) 67 2/9 (22.2%) 2 1/5 (20%) 1
Epistaxis 1/72 (1.4%) 1 1/39 (2.6%) 1 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Hiccups 3/72 (4.2%) 7 1/39 (2.6%) 1 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Hoarseness 1/72 (1.4%) 1 1/39 (2.6%) 1 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Hypoxia 0/72 (0%) 0 1/39 (2.6%) 1 3/64 (4.7%) 3 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Laryngopharyngeal dysesthesia 7/72 (9.7%) 26 4/39 (10.3%) 8 5/64 (7.8%) 8 5/49 (10.2%) 11 0/9 (0%) 0 0/5 (0%) 0
Pharyngolaryngeal pain 0/72 (0%) 0 1/39 (2.6%) 2 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Pleural effusion 0/72 (0%) 0 1/39 (2.6%) 1 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Pleuritic pain 0/72 (0%) 0 1/39 (2.6%) 1 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Pneumonitis 0/72 (0%) 0 0/39 (0%) 0 1/64 (1.6%) 2 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Pneumothorax 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Resp, thoracic, mediastinal - Oth spec 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 2/49 (4.1%) 3 0/9 (0%) 0 0/5 (0%) 0
Respiratory failure 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Tracheal fistula 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Skin and subcutaneous tissue disorders
Alopecia 1/72 (1.4%) 1 2/39 (5.1%) 6 0/64 (0%) 0 1/49 (2%) 1 1/9 (11.1%) 2 0/5 (0%) 0
Dry skin 1/72 (1.4%) 8 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Pruritus 1/72 (1.4%) 1 0/39 (0%) 0 0/64 (0%) 0 1/49 (2%) 1 0/9 (0%) 0 0/5 (0%) 0
Rash maculo-papular 0/72 (0%) 0 1/39 (2.6%) 1 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Skin and subcut tissue disord - Oth spec 1/72 (1.4%) 2 2/39 (5.1%) 3 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Surgical and medical procedures
Surgical and medical proced - Oth spec 0/72 (0%) 0 0/39 (0%) 0 2/64 (3.1%) 2 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Vascular disorders
Flushing 0/72 (0%) 0 0/39 (0%) 0 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 1/5 (20%) 1
Hypertension 1/72 (1.4%) 3 1/39 (2.6%) 1 2/64 (3.1%) 4 2/49 (4.1%) 2 0/9 (0%) 0 1/5 (20%) 1
Hypotension 1/72 (1.4%) 1 3/39 (7.7%) 3 2/64 (3.1%) 2 2/49 (4.1%) 2 0/9 (0%) 0 1/5 (20%) 1
Phlebitis 0/72 (0%) 0 1/39 (2.6%) 1 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Superficial thrombophlebitis 0/72 (0%) 0 1/39 (2.6%) 2 0/64 (0%) 0 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Thromboembolic event 4/72 (5.6%) 5 1/39 (2.6%) 1 1/64 (1.6%) 1 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0
Vascular disorders - Other, specify 0/72 (0%) 0 1/39 (2.6%) 4 1/64 (1.6%) 3 0/49 (0%) 0 0/9 (0%) 0 0/5 (0%) 0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Results Point of Contact

Name/Title Karyn Goodman, M.D.
Organization Alliance for Clinical Trials in Oncology
Phone (212) 639-3983
Email goodmank@mskcc.org
Responsible Party:
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01333033
Other Study ID Numbers:
  • CALGB-80803
  • CDR0000698428
  • NCI-2011-02642
  • U10CA180821
First Posted:
Apr 11, 2011
Last Update Posted:
Nov 3, 2021
Last Verified:
Oct 1, 2021