S0720: Adjuvant Therapy Based on Gene Expression in Stage IA and IB Non-Small Cell Lung Cancer

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00792701
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 85
• Locations: 147
• Arm: 1
• Duration (Months): 89
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy drugs after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, the tumor may not need more treatment until it progresses. In this case, observation may be sufficient.

PURPOSE: This phase II trial is studying how well giving gemcitabine together with cisplatin works in treating patients with stage I non-small cell lung cancer that was removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: cisplatin; Drug: gemcitabine hydrochloride	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To assess the feasibility of assigning adjuvant treatment based on tumoral RRM1 and ERCC1 gene expression in patients with complete surgical resection of stage IA (≥ 2 cm) or IB non-small cell lung cancer.

Secondary

• To estimate the collective 2-year disease-free survival of these patients.

• To assess the frequency and severity of toxicities resulting from the administration of cisplatin and gemcitabine hydrochloride.

• To explore, preliminarily, the relationship between RNA and protein expression of RRM1 and ERCC1, and the relationship between RRM1 and ERCC1 expression in the formalin-fixed and paraffin-embedded tumor specimens, and to generate results on in situ protein expression and other assays for genes involved in drug efficacy.

• To assess the analytical performance of the biomarker assay.

OUTLINE: This is a multicenter study.

Patients are assigned to 1 of 2 treatment arms based on RRM1 and ERCC1 gene expression.

• Arm I (RRM1 ≥ 40 and ERCC1 ≥ 65): Patients undergo active monitoring after surgery with disease assessments at 8, 16, and 24 weeks.

• Arm II (RRM1 < 40 and/or ERCC1 < 65): Beginning within 84 days after surgery, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Tumor samples acquired at the time of surgery are analyzed by immunofluorescence-based automated quantitative analysis for in situ expression of RRM1 and ERCC1. If available, additional samples are assessed using RT-PCR and real-time quantitative PCR for RRM1 and ERCC1 expression levels; polymorphism analysis for RRM1 and ERCC1 expression at the protein level; and tissue microarray analysis of genes associated with DNA synthesis, damage repair, and drug efficacy.

After completion of study therapy, patients are followed every 6 months for up to 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 85 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II ERCC1 and RRM1-Based Adjuvant Therapy Trial in Patients With Stage I Non-Small Cell Lung Cancer (NSCLC)
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Apr 1, 2016
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm II Beginning within 84 days after surgery, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.	Drug: cisplatin; Given IV; Drug: gemcitabine hydrochloride; Given IV

Outcome Measures

Primary Outcome Measures

1. Feasibility of Pharmacogenomics-based Treatment Assignment in the Cooperative Group Setting [From time of registration to 84 days after surgical resection.]

   Feasibility will be assessed both by accrual rate and the percentage of patients successfully assigned to adjuvant chemotherapy or active monitoring.

Secondary Outcome Measures

1. Two-year Disease-free Survival [From time of registration to maximum of 2 years]

2. Frequency and Severity of Toxicities as Assessed by NCI CTCAE v3.0 [From time of registration to maximum of 2 years]

   Patients in the active monitoring arm were not followed for adverse events.

3. Relationship Between RRM1 and ERCC1 Expression in the Formalin-fixed and Paraffin-embedded Tumor Specimens. [From time of registration to maximum of 2 years]

   RRM1 and ERCC1 protein levels are expressed as a simple score with no units.

Other Outcome Measures

1. Analytical Performance of the Biomarker Assay [From time of registration to maximum of 2 years]

2. Generation of Results on in Situ Protein Expression and Other Assays for Genes Involved in Drug Efficacy [From time of registration to maximum of 2 years]

3. Relationship Between RNA and Protein Expression of RRM1 and ERCC1 [From time of registration to maximum of 2 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed non-small cell lung cancer

• Stage IA (longest tumor diameter 2-3 cm) or stage IB disease

• Must have undergone preoperative CT scan of the chest (including the entire liver and adrenals) with IV contrast AND a whole body PET scan or a combined PET/CT scan with no evidence of N1, N2, N3, or M1 disease within 42 days prior to surgery

• A whole body PET scan or a combined PET/CT must be performed within 84 days

• Any finding on PET scan that clinically suggests N1, N2, N3, or M1 disease must have been cleared by further evaluation, including, but not limited to, any of the following:

• Ultrasonography, X-ray radiology, magnetic resonance imaging, or nuclear medicine imaging

• Completely resected (R0) disease by lobectomy, bilobectomy, or pneumonectomy performed by open thoracotomy or video-assisted thoracoscopic surgery within the past 35 days

• Completely excised primary lesion with negative gross and microscopic margins

• At least two mediastinal lymph node stations sampled

• Must have tumor tissue available from the surgical resection specimen AND agree to have treatment assignment determined by a gene expression analysis performed on that tissue

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1

• ANC ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Hemoglobin ≥ 10 mg/dL

• Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)

• AST and ALT ≤ 1.5 times ULN

• Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No other prior malignancy except for the following:

• Adequately treated basal cell or squamous cell skin cancer

• In situ cervical cancer

• Adequately treated stage I-II cancer from which the patient is currently in complete remission

• Any other cancer from which the patient has been disease-free for 5 years

• Willing to provide prior smoking history

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior systemic chemotherapy or biologic therapy for lung cancer

• No prior thoracic radiation therapy (RT) (including RT to the chest wall)

• No other concurrent investigational agents, chemotherapeutic agents, RT, or hormonal therapy

• Steroids administered for antiemesis, adrenal failure, or septic shock OR hormones administered for non-disease-related conditions (e.g., insulin for diabetes) allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hembree Mercy Cancer Center at St. Edward Mercy Medical Center	Fort Smith	Arkansas	United States	72903
2	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
3	Tibotec Therapeutics - Division of Ortho Biotech Products, LP	Marysville	California	United States	95901
4	Valley Medical Oncology Consultants - Pleasanton	Pleasanton	California	United States	94588
5	Sutter Cancer Center at Roseville Medical Center	Roseville	California	United States	95661
6	Sutter Cancer Center	Sacramento	California	United States	95816
7	University of California Davis Cancer Center	Sacramento	California	United States	95817
8	Tahoe Forest Cancer Center	Truckee	California	United States	96161
9	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
10	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
11	Tripler Army Medical Center	Honolulu	Hawaii	United States	96859
12	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois	United States	62002
13	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
14	Sherman Hospital	Elgin	Illinois	United States	60123
15	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
16	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
17	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
18	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
19	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
20	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
21	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
22	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
23	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
24	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas	United States	67905
25	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
26	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
27	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
28	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67401
29	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas	United States	67401
30	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
31	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
32	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
33	CCOP - Wichita	Wichita	Kansas	United States	67214
34	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
35	Caritas St. Elizabeth's Medical Center	Brighton	Massachusetts	United States	02135-2997
36	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
37	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
38	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
39	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan	United States	49017
40	Mecosta County Medical Center	Big Rapids	Michigan	United States	49307
41	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
42	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan	United States	48202
43	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
44	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan	United States	49503
45	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
46	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
47	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
48	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
49	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
50	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
51	Munson Medical Center	Traverse City	Michigan	United States	49684
52	St. John Macomb Hospital	Warren	Michigan	United States	48093
53	Metro Health Hospital	Wyoming	Michigan	United States	49519
54	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi	United States	39581
55	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
56	Saint Louis University Cancer Center	Saint Louis	Missouri	United States	63110
57	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
58	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri	United States	63141
59	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
60	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
61	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
62	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
63	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
64	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59102
65	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
66	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
67	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
68	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
69	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
70	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
71	Northern Montana Hospital	Havre	Montana	United States	59501
72	St. Peter's Hospital	Helena	Montana	United States	59601
73	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
74	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
75	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
76	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
77	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York	United States	10032
78	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
79	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
80	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
81	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
82	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
83	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
84	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
85	Grandview Hospital	Dayton	Ohio	United States	45405
86	Good Samaritan Hospital	Dayton	Ohio	United States	45406
87	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
88	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
89	CCOP - Dayton	Dayton	Ohio	United States	45420
90	Grady Memorial Hospital	Delaware	Ohio	United States	43015
91	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
92	Wayne Hospital	Greenville	Ohio	United States	45331
93	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
94	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
95	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
96	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
97	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
98	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
99	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
100	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
101	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
102	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
103	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
104	Adventist Medical Center	Portland	Oregon	United States	97216
105	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
106	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
107	AnMed Cancer Center	Anderson	South Carolina	United States	29621
108	Cancer Centers of the Carolinas - Easley	Easley	South Carolina	United States	29640
109	Bon Secours St. Francis Health System	Greenville	South Carolina	United States	29601
110	Cancer Centers of the Carolinas - Faris Road	Greenville	South Carolina	United States	29605
111	Cancer Centers of the Carolinas - Grove Commons	Greenville	South Carolina	United States	29605
112	Cancer Centers of the Carolinas - Eastside	Greenville	South Carolina	United States	29615
113	CCOP - Greenville	Greenville	South Carolina	United States	29615
114	Self Regional Cancer Center at Self Regional Medical Center	Greenwood	South Carolina	United States	29646
115	Cancer Centers of the Carolinas - Greer Medical Oncology	Greer	South Carolina	United States	29650
116	Cancer Centers of the Carolinas - Greer Radiation Oncology	Greer	South Carolina	United States	29650
117	Cancer Centers of the Carolinas - Seneca	Seneca	South Carolina	United States	29672
118	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
119	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
120	Cancer Centers of the Carolinas - Spartanburg	Spartanburg	South Carolina	United States	29307
121	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
122	American Fork Hospital	American Fork	Utah	United States	84003
123	Sandra L. Maxwell Cancer Center	Cedar City	Utah	United States	84720
124	Logan Regional Hospital	Logan	Utah	United States	84321
125	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah	United States	84157
126	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah	United States	84403
127	Utah Valley Regional Medical Center - Provo	Provo	Utah	United States	84604
128	Dixie Regional Medical Center - East Campus	Saint George	Utah	United States	84770
129	LDS Hospital	Salt Lake City	Utah	United States	84103
130	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah	United States	84106
131	St. Joseph Cancer Center	Bellingham	Washington	United States	98225
132	Olympic Hematology and Oncology	Bremerton	Washington	United States	98310
133	Columbia Basin Hematology	Kennewick	Washington	United States	99336
134	Skagit Valley Hospital Cancer Care Center	Mount Vernon	Washington	United States	98273
135	Harrison Poulsbo Hematology and Onocology	Poulsbo	Washington	United States	98370
136	Harborview Medical Center	Seattle	Washington	United States	98104
137	Minor and James Medical, PLLC	Seattle	Washington	United States	98104
138	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
139	Group Health Central Hospital	Seattle	Washington	United States	98112
140	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98122-4307
141	Polyclinic First Hill	Seattle	Washington	United States	98122
142	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195
143	Evergreen Hematology and Oncology, PS	Spokane	Washington	United States	99218
144	Northwest Cancer Specialists at Vancouver Cancer Center	Vancouver	Washington	United States	98684
145	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801-2028
146	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
147	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Ralph G. Zinner, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00792701
• Other Study ID Numbers: CDR0000625070; S0720; U10CA032102
• First Posted: Nov 18, 2008
• Last Update Posted: Mar 6, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Southwest Oncology Group: stage I non-small cell lung cancer
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Gemcitabine

Study Results

Participant Flow

Arm/Group Title	Active Monitoring	Gemcitabine Hydrochloride and Cisplatin
Arm/Group Description	Patients undergo active monitoring after surgery with disease assessments at 8, 16, and 24 weeks. Active surveillance: Patients undergo active monitoring	Beginning within 84 days after surgery, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Gemcitabine Hydrochloride: Given IV
Period Title: Overall Study
STARTED	19	66
Eligible	18	63
Eligible and Analyzable	17	44
COMPLETED	0	22
NOT COMPLETED	19	44

Baseline Characteristics

Arm/Group Title	Active Monitoring	Gemcitabine Hydrochloride and Cisplatin	Total
Arm/Group Description	Patients undergo active monitoring after surgery with disease assessments at 8, 16, and 24 weeks. Active surveillance: Patients undergo active monitoring	Beginning within 84 days after surgery, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Gemcitabine Hydrochloride: Given IV	Total of all reporting groups
Overall Participants	18	63	81
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	68.8	63.3	64
Sex: Female, Male (Count of Participants)
Female	7 38.9%	37 58.7%	44 54.3%
Male	11 61.1%	26 41.3%	37 45.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	16 88.9%	58 92.1%	74 91.4%
Unknown or Not Reported	2 11.1%	5 7.9%	7 8.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 5.6%	2 3.2%	3 3.7%
Native Hawaiian or Other Pacific Islander	1 5.6%	1 1.6%	2 2.5%
Black or African American	0 0%	8 12.7%	8 9.9%
White	14 77.8%	52 82.5%	66 81.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 11.1%	0 0%	2 2.5%
Histology (Count of Participants)
Adenocarcinoma	8 44.4%	44 69.8%	52 64.2%
Squamous	8 44.4%	17 27%	25 30.9%
Large Cell	0 0%	1 1.6%	1 1.2%
Bronchioloalveolar	1 5.6%	0 0%	1 1.2%
Other	1 5.6%	1 1.6%	2 2.5%
Performance Status (Count of Participants)
0	13 72.2%	31 49.2%	44 54.3%
1	5 27.8%	32 50.8%	37 45.7%
Smoking History (Count of Participants)
Current	7 38.9%	26 41.3%	33 40.7%
Former	9 50%	30 47.6%	39 48.1%
Never	2 11.1%	7 11.1%	9 11.1%
Stage (Count of Participants)
IA	3 16.7%	22 34.9%	25 30.9%
IB	15 83.3%	41 65.1%	56 69.1%
Weight Loss Last 6 Months (Count of Participants)
<5%	15 83.3%	49 77.8%	64 79%
5-<10%	2 11.1%	7 11.1%	9 11.1%
10-20%	1 5.6%	3 4.8%	4 4.9%
>20%	0 0%	1 1.6%	1 1.2%
Unknown	0 0%	3 4.8%	3 3.7%

Outcome Measures

1. Primary Outcome

Title	Feasibility of Pharmacogenomics-based Treatment Assignment in the Cooperative Group Setting
Description	Feasibility will be assessed both by accrual rate and the percentage of patients successfully assigned to adjuvant chemotherapy or active monitoring.
Time Frame	From time of registration to 84 days after surgical resection.

Outcome Measure Data

Analysis Population Description

Percentage of patients successfully assigned to adjuvant chemotherapy or active monitoring.

Arm/Group Title	All Eligible Patients
Arm/Group Description	All patients who received a treatment assignment within the prespecified timeframe.
Measure Participants	81
Count of Participants [Participants]	71 394.4%

2. Secondary Outcome

Title	Two-year Disease-free Survival
Time Frame	From time of registration to maximum of 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Monitoring	Gemcitabine Hydrochloride and Cisplatin
Arm/Group Description	Patients undergo active monitoring after surgery with disease assessments at 8, 16, and 24 weeks. Active surveillance: Patients undergo active monitoring	Beginning within 84 days after surgery, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Gemcitabine Hydrochloride: Given IV
Measure Participants	17	44
Number (95% Confidence Interval) [percentage of participants]	71 394.4%	83 131.7%

3. Secondary Outcome

Title	Frequency and Severity of Toxicities as Assessed by NCI CTCAE v3.0
Description	Patients in the active monitoring arm were not followed for adverse events.
Time Frame	From time of registration to maximum of 2 years

Outcome Measure Data

Analysis Population Description

Number of Subjects With Greater Than Grade 2 Toxicity Patients in the active monitoring arm were not followed for adverse events.

Arm/Group Title	Gemcitabine Hydrochloride and Cisplatin
Arm/Group Description	Beginning within 84 days after surgery, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Gemcitabine Hydrochloride: Given IV
Measure Participants	43
ALT, SGPT (serum glutamic pyruvic transaminase)	1 5.6%
Anorexia	2 11.1%
Dehydration	1 5.6%
Fatigue (asthenia, lethargy, malaise)	2 11.1%
Febrile neutropenia	2 11.1%
Hearing: pts w/o audiogram not enroll monitor prgm	1 5.6%
Hemoglobin	2 11.1%
Mucositis/stomatitis (clinical exam) - Oral cavity	1 5.6%
Nausea	4 22.2%
Neutrophils/granulocytes (ANC/AGC)	17 94.4%
Platelets	8 44.4%
Pleural effusion (non-malignant)	1 5.6%
Potassium, serum-low (hypokalemia)	1 5.6%
Renal failure	1 5.6%
SVT and nodal arrhythmia - Sinus bradycardia	1 5.6%
Sodium, serum-low (hyponatremia)	2 11.1%
Syncope (fainting)	1 5.6%
Thrombosis/embolism (vascular access-related)	1 5.6%
Thrombosis/thrombus/embolism	1 5.6%
Vomiting	4 22.2%

4. Secondary Outcome

Title	Relationship Between RRM1 and ERCC1 Expression in the Formalin-fixed and Paraffin-embedded Tumor Specimens.
Description	RRM1 and ERCC1 protein levels are expressed as a simple score with no units.
Time Frame	From time of registration to maximum of 2 years

Outcome Measure Data

Analysis Population Description

Protein expression relationships were analyzed in the overall patient population, and not by arm.

Arm/Group Title	All Patients
Arm/Group Description	All registered patients.
Measure Participants	85
RRM1 Protein Score	39.7
ERCC1 Protein Score	41.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Eligible Patients
	Comments
	Type of Statistical Test	Other
	Comments	Correlation
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Correlation Coefficient
	Estimated Value	0.39
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Other Pre-specified Outcome

Title	Analytical Performance of the Biomarker Assay
Time Frame	From time of registration to maximum of 2 years

Outcome Measure Data

Analysis Population Description

Due to lack of funding, the assay was never performed. Thus, this outcome could not be analyzed.

Arm/Group Title	All Patients
Arm/Group Description	All registered patients.
Measure Participants	0

6. Other Pre-specified Outcome

Title	Generation of Results on in Situ Protein Expression and Other Assays for Genes Involved in Drug Efficacy
Time Frame	From time of registration to maximum of 2 years

Outcome Measure Data

Analysis Population Description

Due to lack of funding, the protein expression data were never collected. Thus, this outcome could not be analyzed.

Arm/Group Title	All Patients
Arm/Group Description	All registered patients.
Measure Participants	0

7. Other Pre-specified Outcome

Title	Relationship Between RNA and Protein Expression of RRM1 and ERCC1
Time Frame	From time of registration to maximum of 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Patients
Arm/Group Description	All registered patients.
Measure Participants	81
RRM1 Protein Score	39.7
ERCC1 Protein Score	41.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Eligible Patients
	Comments	Comparing RRM1 levels and ERCC1 levels between all patients.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	.0003
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Correlation Coefficient
	Estimated Value	.39
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From time of registration to maximum of 2 years. Patients in the active monitoring arm were not followed for adverse events.
Adverse Event Reporting Description	All SAEs and AEs Patients in the active monitoring arm were not followed for adverse events.
Arm/Group Title	Gemcitabine Hydrochloride and Cisplatin
Arm/Group Description	Beginning within 84 days after surgery, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Gemcitabine Hydrochloride and Cisplatin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gemcitabine Hydrochloride and Cisplatin
	Affected / at Risk (%)	# Events
Total	2/43 (4.7%)
Injury, poisoning and procedural complications
Thrombosis/embolism (vascular access-related)	1/43 (2.3%)
Metabolism and nutrition disorders
Sodium, serum-low (hyponatremia)	1/43 (2.3%)
Other (Not Including Serious) Adverse Events
	Gemcitabine Hydrochloride and Cisplatin
	Affected / at Risk (%)	# Events
Total	41/43 (95.3%)
Blood and lymphatic system disorders
Hemoglobin	25/43 (58.1%)
Ear and labyrinth disorders
Tinnitus	12/43 (27.9%)
Gastrointestinal disorders
Constipation	16/43 (37.2%)
Diarrhea	10/43 (23.3%)
Heartburn/dyspepsia	6/43 (14%)
Mucositis/stomatitis (clinical exam) - Oral cavity	4/43 (9.3%)
Mucositis/stomatitis (functional/symp) - Oral cav	4/43 (9.3%)
Nausea	34/43 (79.1%)
Vomiting	18/43 (41.9%)
General disorders
Edema: limb	6/43 (14%)
Fatigue (asthenia, lethargy, malaise)	31/43 (72.1%)
Pain-Other	3/43 (7%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	6/43 (14%)
AST, SGOT	10/43 (23.3%)
Alkaline phosphatase	9/43 (20.9%)
Creatinine	3/43 (7%)
Leukocytes (total WBC)	12/43 (27.9%)
Metabolic/Laboratory-Other	4/43 (9.3%)
Neutrophils/granulocytes (ANC/AGC)	28/43 (65.1%)
Platelets	14/43 (32.6%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	3/43 (7%)
Anorexia	18/43 (41.9%)
Calcium, serum-low (hypocalcemia)	4/43 (9.3%)
Dehydration	6/43 (14%)
Glucose, serum-high (hyperglycemia)	15/43 (34.9%)
Glucose, serum-low (hypoglycemia)	3/43 (7%)
Magnesium, serum-low (hypomagnesemia)	3/43 (7%)
Potassium, serum-low (hypokalemia)	6/43 (14%)
Sodium, serum-low (hyponatremia)	8/43 (18.6%)
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - body/general	4/43 (9.3%)
Pain - Back	4/43 (9.3%)
Pain - Joint	4/43 (9.3%)
Pain - Muscle	6/43 (14%)
Nervous system disorders
Dizziness	13/43 (30.2%)
Neuropathy: sensory	7/43 (16.3%)
Pain - Head/headache	12/43 (27.9%)
Taste alteration (dysgeusia)	10/43 (23.3%)
Psychiatric disorders
Insomnia	10/43 (23.3%)
Mood alteration - anxiety	5/43 (11.6%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	3/43 (7%)
Cough	8/43 (18.6%)
Dyspnea (shortness of breath)	7/43 (16.3%)
Hemorrhage, pulmonary/upper respiratory - Nose	3/43 (7%)
Hiccoughs (hiccups, singultus)	3/43 (7%)
Skin and subcutaneous tissue disorders
Dry skin	3/43 (7%)
Hair loss/Alopecia (scalp or body)	7/43 (16.3%)
Pruritus/itching	3/43 (7%)
Rash/desquamation	4/43 (9.3%)
Sweating (diaphoresis)	3/43 (7%)
Vascular disorders
Hypertension	3/43 (7%)
Hypotension	4/43 (9.3%)
Thrombosis/thrombus/embolism	3/43 (7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.