Combination Chemotherapy and Computer-Planned Radiation Therapy in Treating Patients With Unresectable Stage III Non-Small Cell Lung Cancer

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Completed

CT.gov ID

NCT00033553

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arms

Duration (Months)

0.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Computer systems that allow doctors to create a 3-dimensional picture of the tumor to plan treatment may result in more effective radiation therapy. It is not yet known which chemotherapy and/or radiation therapy regimen is more effective in treating non-small cell lung cancer.

PURPOSE: Randomized phase II trial to compare the effectiveness of different combination chemotherapy regimens and 3-dimensional radiation therapy in treating patients who have unresectable stage III non-small cell lung cancer.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: carboplatin Drug: gemcitabine hydrochloride Drug: paclitaxel Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Compare the overall response rate, failure-free survival, and survival of patients with inoperable stage IIIA or IIIB non-small cell lung cancer treated with paclitaxel and carboplatin with concurrent 3-dimensional conformal radiotherapy (3-D XRT) vs gemcitabine and carboplatin with concurrent 3-D XRT.
Compare the toxicity of these regimens in these patients.
Compare the pattern of failure (locoregional vs distant failure) in patients treated with these regimens.
Determine the feasibility of delivering 3-D XRT to patients in this multicenter study.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms.

Arm I: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses. Patients then receive paclitaxel IV over 1 hour followed by carboplatin IV over 30 minutes once weekly and 3-dimensional conformal radiotherapy (3-D XRT) once daily 5 days a week. Treatment repeats weekly for 7 courses.
Arm II: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses. Patients then receive gemcitabine IV over 30 minutes twice weekly and 3-D XRT as in arm

Treatment repeats weekly for 7 courses.

In both arms, treatment continues in the absence of disease progression.

Patients are followed every 2 months for 2 years, every 4 months for 2 years, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 82 patients (41 per treatment arm) will be accrued for this study within 9 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

69 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Induction/Concurrent Chemotherapy and Dose-Escalated Three Dimensional Thoracic Radiation for Patients With Stage III Non Small Cell Lung Cancer: A Randomized Phase II Study

Study Start Date :

Mar 1, 2002

Actual Primary Completion Date :

Sep 1, 2006

Actual Study Completion Date :

Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Paclitaxel + Carboplatin Paclitaxel and carboplatin induction (2 cycles)followed by chemotherapy with the addition of radiotherapy for 7 cycles	Drug: carboplatin Arm A: AUC=6 IV over 30 min for 2 cycles then AUC=2 IV over 30 min q wk for 7 wks Arm B: AUC=5 IV over 30 min for 2 cycles Drug: paclitaxel 225 mg/sq m IV over 3 hrs q 21 days for 2 cycles, then 45 mg/sq m IV over 1 hr q wk for 7 wks Radiation: radiation therapy 3-D XRT 7400 cGy total after induction (during cycles 3-9)
Experimental: Gemcitabine + Carboplatin Gemcitabine and carboplatin induction (2cycles) followed by chemotherapy with the addition of radiotherapy for 7 cycles	Drug: carboplatin Arm A: AUC=6 IV over 30 min for 2 cycles then AUC=2 IV over 30 min q wk for 7 wks Arm B: AUC=5 IV over 30 min for 2 cycles Drug: gemcitabine hydrochloride 1000 mg/sq m IV over 30 min days 1 & 8 repeat q 21 days for 2 cycles; then 35 mg/sq m IV over 30 min 2X wk for 7 wks Radiation: radiation therapy 3-D XRT 7400 cGy total after induction (during cycles 3-9)

Arm

Intervention/Treatment

Experimental: Paclitaxel + Carboplatin

Paclitaxel and carboplatin induction (2 cycles)followed by chemotherapy with the addition of radiotherapy for 7 cycles

Drug: carboplatin

Arm A: AUC=6 IV over 30 min for 2 cycles then AUC=2 IV over 30 min q wk for 7 wks Arm B: AUC=5 IV over 30 min for 2 cycles

Drug: paclitaxel

225 mg/sq m IV over 3 hrs q 21 days for 2 cycles, then 45 mg/sq m IV over 1 hr q wk for 7 wks

Radiation: radiation therapy

3-D XRT 7400 cGy total after induction (during cycles 3-9)

Experimental: Gemcitabine + Carboplatin

Gemcitabine and carboplatin induction (2cycles) followed by chemotherapy with the addition of radiotherapy for 7 cycles

Drug: carboplatin

Arm A: AUC=6 IV over 30 min for 2 cycles then AUC=2 IV over 30 min q wk for 7 wks Arm B: AUC=5 IV over 30 min for 2 cycles

Drug: gemcitabine hydrochloride

1000 mg/sq m IV over 30 min days 1 & 8 repeat q 21 days for 2 cycles; then 35 mg/sq m IV over 30 min 2X wk for 7 wks

Radiation: radiation therapy

3-D XRT 7400 cGy total after induction (during cycles 3-9)

Outcome Measures

Primary Outcome Measures

Response [18 months post treatment]
Response is assessed as failure free survival

Secondary Outcome Measures

Overall Survival [6 years post treatment]
Toxicity [13 weeks]
Toxicity will be assessed during treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
Squamous cell carcinoma
Adenocarcinoma, including bronchoalveolar cell carcinoma
Large cell anaplastic carcinoma, including giant and clear cell carcinoma
Inoperable stage IIIA or IIIB disease
No direct invasion of vertebral body
Tumors adjacent to a vertebral body without bone invasion allowed if all gross disease can be encompassed in radiotherapy boost field
Contralateral mediastinal disease (N3) allowed if all gross disease can be encompassed in radiotherapy boost field
No scalene, supraclavicular, or contralateral hilar node involvement
Transudate, cytologically negative, non-bloody pleural effusion allowed if it can be encompassed in radiotherapy field
No exudative, bloody, or cytologically malignant pleural effusion
Evidence of pleural effusion by chest CT scan but not chest x-ray that is too small to tap allowed
At least 1 unidimensionally measurable lesion
At least 20 mm by conventional techniques OR
At least 10 mm by spiral CT scan
The following are not considered measurable disease:
Bone lesions
Leptomeningeal disease
Ascites
Pleural/pericardial effusion
Abdominal masses that are not confirmed and followed by imaging techniques
Cystic lesions
Tumor lesions in a previously irradiated field

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-1

Life expectancy:

Not specified

Hematopoietic:

Granulocyte count at least 1,500/mm3
Platelet count at least 100,000/mm3

Hepatic:

Bilirubin less than 1.5 mg/dL
AST less than 2 times upper limit of normal

Renal:

Creatinine clearance 20-130 mL/min for females
Creatinine clearance 20-150 mL/min for males

Pulmonary:

FEV1 at least 1.2 L

Other:

Not pregnant or nursing
Fertile patients must use effective contraception
No other currently active malignancy (defined as completed prior therapy and considered to be at less than 30% risk of relapse) except non-melanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior chemotherapy for NSCLC
No other concurrent chemotherapy

Endocrine therapy:

No concurrent hormonal therapy except steroids for adrenal failure or septic shock, hormones for non-disease-related conditions (e.g., insulin for diabetes), or glucocorticosteroids as antiemetics

Radiotherapy:

See Disease Characteristics
No prior radiotherapy for NSCLC

Surgery:

At least 2 weeks since prior exploratory thoracotomy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northeast Alabama Regional Medical Center	Anniston	Alabama	United States	36207
2	Rebecca and John Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
3	Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
4	Naval Medical Center - San Diego	San Diego	California	United States	92134-3202
5	Veterans Affairs Medical Center - San Diego	San Diego	California	United States	92161
6	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
7	Veterans Affairs Medical Center - San Francisco	San Francisco	California	United States	94121
8	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
9	Lombardi Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
10	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307-5001
11	Veterans Affairs Medical Center - Washington, DC	Washington	District of Columbia	United States	20422
12	Broward General Medical Center	Fort Lauderdale	Florida	United States	33316
13	Memorial Regional Cancer Center at Memorial Regional Hospital	Hollywood	Florida	United States	33021
14	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
15	Florida Hospital Cancer Institute	Orlando	Florida	United States	32804
16	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois	United States	60612
17	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
18	Louis A. Weiss Memorial Hospital	Chicago	Illinois	United States	60640
19	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615-7828
20	West Suburban Center for Cancer Care	River Forest	Illinois	United States	60305
21	Fort Wayne Medical Oncology and Hematology, Incorporated	Fort Wayne	Indiana	United States	46885-5099
22	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
23	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1009
24	Baptist Hospital East - Louisville	Louisville	Kentucky	United States	40207
25	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
26	UMASS Memorial Cancer Center - University Campus	Worcester	Massachusetts	United States	01655
27	Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph	Saint Joseph	Michigan	United States	49085
28	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55417
29	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
30	Veterans Affairs Medical Center - Columbia (Truman Memorial)	Columbia	Missouri	United States	65201
31	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
32	CCOP - Kansas City	Kansas City	Missouri	United States	64131
33	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
34	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
35	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-7680
36	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
37	Veterans Affairs Medical Center - Las Vegas	Las Vegas	Nevada	United States	89106
38	New Hampshire Oncology-Hematology, PA - Hooksett	Hooksett	New Hampshire	United States	03106
39	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
40	Cancer Institute of New Jersey at the Cooper University Hospital	Camden	New Jersey	United States	08103
41	Veterans Affairs Medical Center - Buffalo	Buffalo	New York	United States	14215
42	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
43	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	East Syracuse	New York	United States	13057
44	Elmhurst Hospital Center	Elmhurst	New York	United States	11373
45	Queens Cancer Center of Queens Hospital	Jamaica	New York	United States	11432
46	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
47	North Shore University Hospital	Manhasset	New York	United States	11030
48	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
49	New York Weill Cornell Cancer Center at Cornell University	New York	New York	United States	10021
50	Mount Sinai Medical Center	New York	New York	United States	10029
51	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
52	Veterans Affairs Medical Center - Syracuse	Syracuse	New York	United States	13210
53	Veterans Affairs Medical Center - Asheville	Asheville	North Carolina	United States	28805
54	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
55	NorthEast Oncology Associates - Concord	Concord	North Carolina	United States	28025
56	Veterans Affairs Medical Center - Durham	Durham	North Carolina	United States	27705
57	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
58	Cape Fear Valley Health System	Fayetteville	North Carolina	United States	28302-2000
59	CCOP - Southeast Cancer Control Consortium	Goldsboro	North Carolina	United States	27534-9479
60	Lenoir Memorial Cancer Center	Kinston	North Carolina	United States	28503-1678
61	Comprehensive Cancer Center at Moore Regional Hospital	Pinehurst	North Carolina	United States	28374
62	Zimmer Cancer Center at New Hanover Regional Medical Center	Wilmington	North Carolina	United States	28402-9025
63	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157-1082
64	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University	Columbus	Ohio	United States	43210-1240
65	Oklahoma University Medical Center	Oklahoma City	Oklahoma	United States	73104
66	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania	United States	15224
67	Lifespan: The Miriam Hospital	Providence	Rhode Island	United States	02906
68	Veterans Affairs Medical Center - Dallas	Dallas	Texas	United States	75219
69	Vermont Cancer Center at University of Vermont	Burlington	Vermont	United States	05401-3498
70	Martha Jefferson Hospital	Charlottesville	Virginia	United States	22902
71	Virginia Oncology Associates - Norfolk	Norfolk	Virginia	United States	23502
72	MBCCOP - Massey Cancer Center	Richmond	Virginia	United States	23298-0037
73	Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke	Roanoke	Virginia	United States	24014
74	St. Mary's Medical Center	Huntington	West Virginia	United States	25701