4B951, Combination Chemotherapy in Treating Patients With Bladder Cancer

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00005047
• Collaborator: National Cancer Institute (NCI) (NIH), NCIC Clinical Trials Group (Other), University of Southern California (Other)
• Enrollment: 521
• Locations: 74
• Arms: 4
• Actual Duration (Months): 208
• Patients Per Site: 7
• Patients Per Site Per Month: 0

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. Combining more than one drug may kill more tumor cells. It is not yet known whether combination chemotherapy is more effective than observation alone in treating bladder cancer.

PURPOSE: This randomized phase III trial is studying combination chemotherapy to see how well it works compared to observation alone in treating patients with bladder cancer.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer	Drug: cisplatin; Drug: doxorubicin hydrochloride; Drug: methotrexate; Drug: vinblastine	Phase 3

Detailed Description

OBJECTIVES:

• Compare the recurrence-free and overall survival in patients with transitional cell carcinoma of the bladder with p53 gene alterations treated with methotrexate, vinblastine, doxorubicin, and cisplatin vs observation alone.

• Compare the recurrence-free and overall survival in patients with or without p53 gene alterations treated with observation alone.

• Examine the expression of p53 and other genes, particularly RB, p21, and p16, involved in cell cycle regulation that may be involved in the response to chemotherapy in these patients.

• Correlate p53 mutational gene status with p53 protein expression by immunohistochemistry, outcome (recurrence-free and overall survival), response to chemotherapy, and expression of key molecules in the p53-mediated apoptotic pathway in patients treated with this regimen vs observation alone.

OUTLINE: This is a randomized, multicenter study. Patients are assigned to 1 of 2 treatment groups based on the status of the p53 gene in the bladder tumor.

• Group A (p53 gene alteration, defined by greater than 10% nuclear reactivity): Patients are stratified according to age (under 65 vs 65 and over), stage (P1 vs P2a vs P2b), grade (1 or 2 vs 3 or 4), and p21 status. Patients are randomized to 1 of 2 treatment arms within 10 weeks after radical cystectomy and bilateral pelvic lymphadenectomy and within 2 weeks after registration.

• Arm I: Within 2 weeks after randomization, patients receive methotrexate IV on days 1, 15, and 22; vinblastine IV on days 2, 15, and 22; and doxorubicin IV and cisplatin IV on day 2. Treatment repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients undergo observation for recurrence but do not receive adjuvant chemotherapy after surgery.

Patients who are eligible for randomization but decline to be randomized undergo observation for recurrence.

• Group B (p53 gene normal, defined by less than 10% nuclear reactivity): Patients undergo observation for recurrence but do not receive adjuvant chemotherapy after surgery.

Patients are followed every 6 months for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 800 patients will be accrued for this study within 4.75 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 521 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: MVAC (Methotrexate, Vinblastine, Adriamycin, and Cisplatin) in Organ-Confined Bladder Cancer Based on p53 Status
• Actual Study Start Date: Aug 1, 1997
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I: M-VAC x 3 Patients with altered (+) p53, reconsented to randomization, randomized to three cycles of MVAC	Drug: cisplatin; Drug: doxorubicin hydrochloride; Drug: methotrexate; Drug: vinblastine
No Intervention: Arm II: Observation Patients with altered (+) p53, reconsented to randomization, randomized to observation
No Intervention: Arm III: Observation Patients with unaltered (-) p53
No Intervention: Arm IV: Observation Patients with altered (+) p53, patients did not consent to randomization

Outcome Measures

Primary Outcome Measures

1. Probability of Recurring [5 years]

   p53 positive patients randomized to MVAC (arm I) compared to p53 positive patients randomized to observation (arm II). Time from registration to the first observation of disease recurrence, censoring patients who died of unrelated causes. Probabilities of recurring were based on cumulative incidence curves. Recurrence is defined as first radiological appearance of bladder cancer, per local standard of care.

Secondary Outcome Measures

1. Probability of Overall Survival [5 years]

   p53 positive patients randomized to MVAC (arm I) compared to p53 positive patients randomized to observation (arm II). Survival is calculated from registration to death due to any cause. Probabilities of survival were based on the Kaplan-Meier product-limit method.

2. Probability of Recurrence [5 years]

   Patients with tumors demonstrating alteration in p53 compared to patients with no p53 alterations. Probabilities of recurring were based on cumulative incidence curves. Recurrence is defined as first radiological appearance of bladder cancer, per local standard of care.

3. Probability of Overall Survival [5 years]

   Patients with tumors demonstrating alteration in p53 compared to patients with no p53 alterations. Probabilities of survival were based on the Kaplan-Meier product-limit method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically proven organ confined transitional cell carcinoma (TCC) of the bladder

• Must have undergone radical cystectomy and bilateral pelvic lymphadenectomy with pathologic stage from definitive cystectomy specimen of P1, P2a, or P2b and N0, M0 TCC with or without squamous/glandular differentiation (no adenocarcinoma, squamous cell carcinoma, or small cell carcinoma)

• Margins must be negative for invasive or in situ TCC

• In situ TCC in the urethra or ureter(s) allowed provided margins are negative

• Clinical stage T1, T2a, or T2b based on transurethral resection bladder tumor specimen with P0 or PIS and N0, M0 TCC allowed

• Incidental pT2a (Gleason score no greater than 7), pT2b (Gleason score no greater than 7), or pT2c (Gleason score no greater than 7) adenocarcinoma of the prostate allowed

• No invasive tumor into ureter(s) or urethra

• Must have potentially curable disease

• Must register within 9 weeks after surgery

• No metastatic disease by physical exam and chest x-ray or CT scan of the chest

• Eligible for randomization if:

• p53 gene alteration present

• Randomization occurs within 10 weeks after surgery

• Those who are randomized to receive (MVAC) methotrexate, vinblastine, doxorubicin, and cisplatin begin MVAC within 12 weeks after cystectomy

• No metastatic disease by physical exam and chest x-ray or CT scan of the chest

• No prohibitive medical risk for chemotherapy

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• ECOG 0-1 OR

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• WBC at least 4,000/mm^3

• Platelet count at least 150,000/mm^3

Hepatic

• SGOT or SGPT no greater than 2 times normal

• Alkaline phosphatase no greater than 2 times normal

• Bilirubin normal

Renal

• Creatinine no greater than 1.8 mg/dL OR

• Creatinine clearance at least 50 mL/min

• Blood urea nitrogen normal

Cardiovascular

• No serious arrhythmias

• No congestive heart disease with New York Heart Association class III or IV status

• Randomization group:

• Ejection fraction must be at least 50% by MUGA scan if there is a clinical concern regarding the patient's cardiac status

Other

• No other malignancy (including synchronous papillary or invasive upper urinary tract malignancy) within the past 5 years except incidental prostate cancer (found at cystectomy), basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix

• No concurrent advanced medical illness or psychologic disease

• No prohibitive medical risk for chemotherapy

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

• No prior systemic chemotherapy for bladder cancer

• At least 5 years since other prior systemic chemotherapy

• Prior intravesical therapy allowed

• Randomization group:

• Prior intravesical therapy allowed if administered prior to cystectomy

Endocrine therapy

• Not specified

Radiotherapy

• No prior pelvic irradiation

Surgery

• See Disease Characteristics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner Thunderbird Medical Center	Glendale	Arizona	United States	85306
2	Banner Good Samaritan Medical Center	Phoenix	Arizona	United States	85006
3	CCOP - Western Regional, Arizona	Phoenix	Arizona	United States	85006
4	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90089-9181
5	North Colorado Medical Center	Greeley	Colorado	United States	80631
6	McKee Medical Center	Loveland	Colorado	United States	80539
7	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois	United States	62002
8	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
9	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
10	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
11	Cancer Center of Kansas, P.A. - Chanute	Chanute	Kansas	United States	66720
12	Cancer Center of Kansas, P.A. - Dodge City	Dodge City	Kansas	United States	67801
13	Cancer Center of Kansas, P.A. - El Dorado	El Dorado	Kansas	United States	67042
14	Veterans Affairs Medical Center - Kansas City	Kansas City	Kansas	United States	64128
15	Cancer Center of Kansas, P.A. - Kingman	Kingman	Kansas	United States	67068
16	Southwest Medical Center	Liberal	Kansas	United States	67901
17	Cancer Center of Kansas, P.A. - Newton	Newton	Kansas	United States	67114
18	Cancer Center of Kansas, P.A. - Parsons	Parsons	Kansas	United States	67357
19	Cancer Center of Kansas, P.A. - Pratt	Pratt	Kansas	United States	67124
20	Cancer Center of Kansas, P.A. - Salina	Salina	Kansas	United States	67042
21	Salina Regional Health Center	Salina	Kansas	United States	67401
22	Cancer Center of Kansas, P.A. - Wellington	Wellington	Kansas	United States	67152
23	Associates in Womens Health, P.A. - North Review	Wichita	Kansas	United States	67203
24	Cancer Center of Kansas, P.A. - Medical Arts Tower	Wichita	Kansas	United States	67208
25	Cancer Center of Kansas, P.A. - Wichita	Wichita	Kansas	United States	67214
26	CCOP - Wichita	Wichita	Kansas	United States	67214
27	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
28	Cancer Center of Kansas, P.A. - Winfield	Winfield	Kansas	United States	67156
29	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana	United States	71101
30	Feist-Weiller Cancer Center at Louisiana State University Health Sciences	Shreveport	Louisiana	United States	71130-3932
31	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
32	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan	United States	48073
33	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Cape Girardeau	Missouri	United States	63701
34	St. Francis Medical Center	Cape Girardeau	Missouri	United States	63701
35	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
36	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri	United States	63141
37	Big Sky Oncology	Great Falls	Montana	United States	59405
38	Sletten Regional Cancer Institute	Great Falls	Montana	United States	59405
39	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York	United States	10032
40	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
41	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
42	Grandview Hospital	Dayton	Ohio	United States	45405
43	Good Samaritan Hospital	Dayton	Ohio	United States	45406
44	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
45	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
46	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
47	CCOP - Dayton	Dayton	Ohio	United States	45429
48	Community Oncology Group at Cleveland Clinic Cancer Center	Independence	Ohio	United States	44131
49	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
50	Middletown Regional Hospital	Middletown	Ohio	United States	45044
51	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
52	Cleveland Clinic - Wooster	Wooster	Ohio	United States	44691
53	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
54	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
55	Wilford Hall Medical Center	Lackland Air Force Base	Texas	United States	78236
56	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas	United States	78209
57	Cancer Therapy and Research Center	San Antonio	Texas	United States	78229
58	University Hospital - San Antonio	San Antonio	Texas	United States	78229
59	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811
60	Sentara Cancer Institute at Sentara Norfolk General Hospital	Norfolk	Virginia	United States	23507
61	St. Joseph Hospital Community Cancer Center	Bellingham	Washington	United States	98225
62	Olympic Hematology and Oncology	Bremerton	Washington	United States	98310
63	Skagit Valley Hospital Cancer Care Center	Mount Vernon	Washington	United States	98273
64	CCOP - Virginia Mason Research Center	Seattle	Washington	United States	98101
65	Group Health Central Hospital	Seattle	Washington	United States	98104
66	Harborview Medical Center	Seattle	Washington	United States	98104
67	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109-1024
68	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98114
69	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195-6043
70	North Puget Oncology at United General Hospital	Sedro-Woolley	Washington	United States	98284
71	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
72	Wenatchee Valley Clinic	Wenatchee	Washington	United States	98801
73	Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital	Parkersburg	West Virginia	United States	26102
74	Toronto Sunnybrook Regional Cancer Centre at Sunnybrook and Women's College Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)
• NCIC Clinical Trials Group
• University of Southern California

Investigators

• Study Chair: Richard J. Cote, MD, FRCPath, University of Southern California
• Study Chair: Laurence H. Klotz, MD, Toronto Sunnybrook Regional Cancer Centre
• Study Chair: Seth P Lerner, MD, Baylor College of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00005047
• Other Study ID Numbers: CDR0000067639; LAC-USC-4B951; SWOG-4B951; NCI-G00-1715; NYU-9852; CAN-NCIC-BL10; CCCWFU-88198; U10CA032102
• First Posted: Jan 27, 2003
• Last Update Posted: Jun 8, 2017
• Last Verified: May 1, 2017

• Keywords provided by Southwest Oncology Group: stage I bladder cancer; stage II bladder cancer; transitional cell carcinoma of the bladder
• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vinblastine

Study Results

Participant Flow

Pre-assignment Detail	Patients with stage pT1/T2N0M0 urothelial cancer who had undergone a radical cystectomy within the prior 9 weeks were eligible for enrollment. Twenty-two patients who were registered were never assigned to a group after enrolling due to: missing baseline documentation (5), incorrect disease stage (13), and patient withdrawal (4).

Arm/Group Title	Arm I: M-VAC x 3	Arm II: Observation	Arm III: Observation	Arm IV: Observation
Arm/Group Description	Patients with altered (+) p53, reconsented to randomization, randomized to three cycles of MVAC cisplatin doxorubicin hydrochloride methotrexate vinblastine	Patients with altered (+) p53, reconsented to randomization, randomized to observation	Patients with unaltered (-) p53	Patients with altered (+) p53, patients did not consent to randomization
Period Title: Overall Study
STARTED	58	56	227	158
COMPLETED	39	56	227	158
NOT COMPLETED	19	0	0	0

Baseline Characteristics

Arm/Group Title	Arm I: M-VAC x 3	Arm II: Observation	Arm III: Observation	Arm IV: Observation	Total
Arm/Group Description	p53 positive, randomized to 3 cycles of adjuvant combination methotrexate, vinblastine, doxorubicin and cisplatin (MVAC)	p53 positive, randomized to observation/no intervention	p53 negative, assigned to observation/no intervention	p53 positive, refused random assignment, assigned to observation/no intervention	Total of all reporting groups
Overall Participants	58	56	227	158	499
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	37 63.8%	41 73.2%	127 55.9%	81 51.3%	286 57.3%
>=65 years	21 36.2%	15 26.8%	100 44.1%	77 48.7%	213 42.7%
Sex: Female, Male (Count of Participants)
Female	7 12.1%	9 16.1%	49 21.6%	34 21.5%	99 19.8%
Male	51 87.9%	47 83.9%	178 78.4%	124 78.5%	400 80.2%
Race/Ethnicity, Customized (Count of Participants)
White	52 89.7%	49 87.5%	203 89.4%	150 94.9%	454 91%
Black	4 6.9%	1 1.8%	13 5.7%	4 2.5%	22 4.4%
Asian	0 0%	2 3.6%	6 2.6%	1 0.6%	9 1.8%
Hispanic	1 1.7%	4 7.1%	3 1.3%	3 1.9%	11 2.2%
Other	1 1.7%	0 0%	2 0.9%	0 0%	3 0.6%
Stage (Count of Participants)
pT1	21 36.2%	16 28.6%	87 38.3%	61 38.6%	185 37.1%
pT2 and pT2a	37 63.8%	40 71.4%	140 61.7%	97 61.4%	314 62.9%
Grade (Count of Participants)
1 or 2	2 3.4%	1 1.8%	16 7%	5 3.2%	24 4.8%
3 or 4	56 96.6%	55 98.2%	210 92.5%	152 96.2%	473 94.8%
missing	0 0%	0 0%	1 0.4%	1 0.6%	2 0.4%
No. of nodes identified (Count of Participants)
<15 nodes	22 37.9%	14 25%	68 30%	64 40.5%	168 33.7%
>= 15 nodes	36 62.1%	42 75%	159 70%	94 59.5%	331 66.3%
p21 status (Count of Participants)
Absent	24 41.4%	22 39.3%	35 15.4%	64 40.5%	145 29.1%
Present	34 58.6%	34 60.7%	190 83.7%	92 58.2%	350 70.1%
missing	0 0%	0 0%	2 0.9%	2 1.3%	4 0.8%
Lymphovascular invasion (Count of Participants)
No	33 56.9%	25 44.6%	117 51.5%	84 53.2%	259 51.9%
Yes	13 22.4%	14 25%	46 20.3%	29 18.4%	102 20.4%
Unknown	12 20.7%	17 30.4%	64 28.2%	45 28.5%	138 27.7%
Bladder carcinoma in situ (Count of Participants)
No	16 27.6%	12 21.4%	60 26.4%	36 22.8%	124 24.8%
Yes	34 58.6%	32 57.1%	137 60.4%	99 62.7%	302 60.5%
Unknown	8 13.8%	12 21.4%	30 13.2%	23 14.6%	73 14.6%

Outcome Measures

1. Primary Outcome

Title	Probability of Recurring
Description	p53 positive patients randomized to MVAC (arm I) compared to p53 positive patients randomized to observation (arm II). Time from registration to the first observation of disease recurrence, censoring patients who died of unrelated causes. Probabilities of recurring were based on cumulative incidence curves. Recurrence is defined as first radiological appearance of bladder cancer, per local standard of care.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I: M-VAC x 3	Arm II: Observation
Arm/Group Description	Patients with altered (+) p53, reconsented to randomization, randomized to three cycles of MVAC cisplatin doxorubicin hydrochloride methotrexate vinblastine	Patients with altered (+) p53, reconsented to randomization, randomized to observation
Measure Participants	58	56
Median (Standard Error) [probability]	0.85 (0.05)	0.84 (0.06)

2. Secondary Outcome

Title	Probability of Overall Survival
Description	p53 positive patients randomized to MVAC (arm I) compared to p53 positive patients randomized to observation (arm II). Survival is calculated from registration to death due to any cause. Probabilities of survival were based on the Kaplan-Meier product-limit method.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I: M-VAC x 3	Arm II: Observation
Arm/Group Description	Patients with altered (+) p53, reconsented to randomization, randomized to three cycles of MVAC cisplatin doxorubicin hydrochloride methotrexate vinblastine	Patients with altered (+) p53, reconsented to randomization, randomized to observation
Measure Participants	58	56
Median (Standard Error) [probability]	0.87 (0.05)	0.84 (0.05)

3. Secondary Outcome

Title	Probability of Recurrence
Description	Patients with tumors demonstrating alteration in p53 compared to patients with no p53 alterations. Probabilities of recurring were based on cumulative incidence curves. Recurrence is defined as first radiological appearance of bladder cancer, per local standard of care.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

This analysis compares p53 positive patients (combined arms I, II, and IV) to p53 negative patients (arm III).

Arm/Group Title	p53 Positive Patients	p53 Negative Patients
Arm/Group Description	Arm I: Patients with altered (+) p53, reconsented to randomization, randomized to three cycles of MVAC Arm II: Patients with altered (+) p53, reconsented to randomization, randomized to observation Arm IV: Patients with altered (+) p53, patients did not consent to randomization	Arm III: Observation; Patients with unaltered (-) p53
Measure Participants	272	227
Median (Standard Error) [probability]	0.83 (0.03)	0.77 (0.03)

4. Secondary Outcome

Title	Probability of Overall Survival
Description	Patients with tumors demonstrating alteration in p53 compared to patients with no p53 alterations. Probabilities of survival were based on the Kaplan-Meier product-limit method.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

This analysis compares p53 positive patients (combined arms I, II, and IV) to p53 negative patients (arm III).

Arm/Group Title	p53 Positive Patients	p53 Negative Patients
Arm/Group Description	Arm I: Patients with altered (+) p53, reconsented to randomization, randomized to three cycles of MVAC Arm II: Patients with altered (+) p53, reconsented to randomization, randomized to observation Arm IV: Patients with altered (+) p53, patients did not consent to randomization	Arm III: Observation; Patients with unaltered (-) p53
Measure Participants	272	227
Median (Standard Error) [probability]	0.82 (0.03)	0.84 (0.03)

Adverse Events

Time Frame	5 years: every 3 months for the first year, every 6 months for the following 4 years
Adverse Event Reporting Description	Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
Arm/Group Title	Arm I: M-VAC x 3		Arm II: Observation		Arm III: Observation		Arm IV: Observation
Arm/Group Description	Patients with altered (+) p53, reconsented to randomization, randomized to three cycles of MVAC cisplatin doxorubicin hydrochloride methotrexate vinblastine		Patients with altered (+) p53, reconsented to randomization, randomized to observation		Patients with unaltered (-) p53		Patients with altered (+) p53, patients did not consent to randomization
All Cause Mortality
	Arm I: M-VAC x 3		Arm II: Observation		Arm III: Observation		Arm IV: Observation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/58 (20.7%)		9/56 (16.1%)		41/227 (18.1%)		36/158 (22.8%)
Serious Adverse Events
	Arm I: M-VAC x 3		Arm II: Observation		Arm III: Observation		Arm IV: Observation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/46 (0%)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Arm I: M-VAC x 3		Arm II: Observation		Arm III: Observation		Arm IV: Observation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/46 (76.1%)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Blood and lymphatic system disorders
Decreased WBC	14/46 (30.4%)		0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Lymphopenia	4/46 (8.7%)		0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Neutropenia	31/46 (67.4%)		0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Gastrointestinal disorders
Nausea	6/46 (13%)		0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Stomatitis	5/46 (10.9%)		0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Vomiting	5/46 (10.9%)		0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
General disorders
Fatigue	6/46 (13%)		0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0

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.