Chemotherapy and Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Neuroblastoma

Sponsor

Gesellschaft fur Padiatrische Onkologie und Hamatologie - Germany (Other)

Overall Status

Completed

CT.gov ID

NCT00017225

Collaborator

(none)

Locations

57.1

Duration (Months)

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. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. Combining these therapies may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining chemotherapy and radiation therapy with or without peripheral stem cell transplantation in treating patients who have neuroblastoma.

Condition or Disease	Intervention/Treatment	Phase
Neuroblastoma	Biological: filgrastim Drug: carboplatin Drug: cisplatin Drug: cyclophosphamide Drug: dacarbazine Drug: doxorubicin hydrochloride Drug: etoposide Drug: ifosfamide Drug: melphalan Drug: tretinoin Drug: vincristine sulfate Drug: vindesine Procedure: autologous bone marrow transplantation Procedure: conventional surgery Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Determine the frequency of spontaneous remission in pediatric patients with localized neuroblastoma.
Determine the course of regression in patients with spontaneous remission.
Determine the event-free survival rate of patients with high-risk neuroblastoma treated with maintenance chemotherapy OR consolidation chemotherapy followed by autologous stem cell rescue.
Determine if a correlation exists between long-term overall survival and catecholamine response in these high-risk patients.
Determine if a correlation exists between cytotoxic and conditioning chemotherapies, in terms of bone marrow toxicity, in these high-risk patients.

OUTLINE: This is a multicenter study. Patients are stratified according to risk (low vs standard vs high).

Observation stratum (low risk): Patients undergo surgical biopsy followed by observation for 6-12 months. Patients may also undergo second-look surgery. Patients with tumor regression receive no further therapy. Patients with disease progression or no tumor regression receive standard-risk chemotherapy as in the standard-risk stratum.
Standard-risk stratum: Patients undergo surgical biopsy. Patients at least 6 months of age receive 1 course of chemotherapy comprising cisplatin IV and etoposide IV continuously on days 1-4 and vindesine IV over 1 hour on day 1. Patients then receive 1 course of chemotherapy comprising vincristine IV over 1 hour on days 1 and 8, dacarbazine IV over 1 hour on days 1-5, ifosfamide IV continuously on days 1-5, and doxorubicin IV over 4 hours on days 6 and 7.

Patients under 6 months of age receive doxorubicin IV over 30 minutes and vincristine IV on days 1, 3, and 5 and cyclophosphamide IV over 5 minutes on days 1-7. Treatment repeats every 3 weeks for 2 courses in the absence of unacceptable toxicity.

After chemotherapy, patients may undergo second-look surgery followed by 2 additional courses of chemotherapy as above. Patients with complete response or very good partial response receive no further therapy. Patients with partial response, minimal response, no response, or progressive disease undergo local radiotherapy daily 5 days a week for approximately 6 weeks. Patients with no response after radiotherapy may then receive therapy as in the high-risk stratum.

High-risk stratum: Patients undergo surgical biopsy. Patients at least 6 months of age receive induction chemotherapy comprising cisplatin, etoposide, and vindesine as in the standard-risk stratum combined with filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 8 and continuing until blood counts recover. Patients also receive alternating courses of vincristine, dacarbazine, ifosfamide, and doxorubicin as in the standard-risk stratum combined with G-CSF SC daily beginning on day 9 and continuing until blood counts recover. Treatment repeats every 3 weeks for up to 6 courses in the absence of unacceptable toxicity.

Patients under 6 months of age receive 2 courses of induction chemotherapy as in the standard-risk stratum followed by 4 courses of alternating chemotherapy as above.

Patients may also undergo second-look surgery.

Patients then receive consolidation chemotherapy comprising melphalan IV over 30 minutes on days -8 to -5, etoposide IV over 4 hours on day -4, and carboplatin IV over 1 hour on days -4 to -2. Patients undergo autologous stem cell transplantation (ASCT) on day 0. Patients also receive G-CSF SC or IV over 2 hours daily beginning on day 0. Patients may then undergo radiotherapy daily 5 days a week for 6 weeks.

Patients who were diagnosed less than 1 year ago and who do not demonstrate MYCN amplication receive maintenance chemotherapy comprising oral cyclophosphamide on days 1-8 (instead of consolidation chemotherapy and ASCT as above). Treatment repeats every 3 weeks for 4 courses.

Beginning 4-6 weeks after transplantation or 4 weeks after initiation of the last course of maintenance chemotherapy, all patients receive consolidation therapy with oral tretinoin 3 times daily on days 1-14. Treatment repeats every 28 days for 6 courses followed by a 3-month rest. Patients then receive 3 additional courses.

Patients are followed at 6 weeks, every 3 months for 5 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: Approximately 130 patients (50 in high-risk stratum, 15 in standard-risk stratum, and 65 in observation stratum) will be accrued for this study within 1 year.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

Neuroblastoma Study Phase II Study of Various Therapies in Patients With Neuroblastoma

Study Start Date :

May 1, 1997

Actual Study Completion Date :

Feb 1, 2002

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 20 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed neuroblastoma
Observation stratum:
MYCN gene not amplified
Infants with stage I-IVS disease OR
Over 1 year of age and stage I or II resectable disease
Standard-risk stratum:
MYCN gene not amplified
Infants with serious symptoms and stage II-IVS disease OR
Over 1 year of age with stage II or III unresectable disease
High-risk stratum:
Stage IV disease OR
Stage I-IVS MYCN gene-amplified disease

PATIENT CHARACTERISTICS:

Age:

20 and under

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

Not specified

Renal:

No kidney insufficiency

Cardiovascular:

No cardiac insufficiency

Other:

Not pregnant
Fertile patients must use effective contraception
No other serious illness

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior chemotherapy within 6 months after diagnosis

Endocrine therapy:

Not specified

Radiotherapy:

Not specified

Surgery:

Not specified

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Urologische Klinik - Universitaetsklinikum Aachen	Aachen	Germany	D-52074
2	Kinderkrankenhaus Josefinum	Augsburg	Germany	86154
3	Zentralklinikum Augsburg	Augsburg	Germany	DOH-86156
4	Caritaskrankenhaus	Bad Mergentheim	Germany	97980
5	Klinikum Bayreuth	Bayreuth	Germany	95445
6	Helios Klinikum Berlin	Berlin	Germany	13122
7	Charite - Campus Virchow Klinikum	Berlin	Germany	D-13353
8	Krankenanstalten Gilead	Biefeld	Germany	33617
9	Kinderklinik der Universitaet-Bonn	Bonn	Germany	DOH-53113
10	Stadt Klinikum - Howedestrase	Braunschweig	Germany	38118
11	Zentralkrankenhaus	Bremen	Germany	D-28205
12	Klinikum Chemnitz GMBH	Chemnitz	Germany	D-09116
13	Klinikum Coburg	Coburg	Germany	96450
14	Medizinische Universitaetsklinik I	Cologne	Germany	D-50924
15	Carl - Thiem - Klinkum Cottbus	Cottbus	Germany	D-03048
16	Vestische Kinderklinik	Datteln	Germany	45704
17	Klinikum Lippe - Detmold	Detmold	Germany	32756
18	Stadt. Kliniken	Dortmund	Germany	44123
19	Stadt. KH Dresden - Neustadt	Dresden	Germany	01229
20	Universitatsklinikum Carl Gustav Carl Carus	Dresden	Germany	D-01307
21	Universitaetsklinik Duesseldorf	Duesseldorf	Germany	D-40225
22	Helios Klinikum Erfurt GmbH	Erfurt	Germany	99012
23	Universitaets - Kinderklinik	Erlangen	Germany	D-91054
24	Universitaetsklinikum Essen	Essen	Germany	D-45122
25	Klinikum der J.W. Goethe Universitaet	Frankfurt	Germany	D-60590
26	Universitaetskinderklinik - Universitaetsklinikum Freiburg	Freiburg	Germany	79106
27	Stadt. Kinderklinik	Gelsenkirchen	Germany	45892
28	Kinderklinik	Giessen	Germany	D-35385
29	Universitaetsklinikum Goettingen	Goettingen	Germany	D-37075
30	Universitats - Kinderklinik	Greiswald	Germany	17487
31	Kreiskrankenhaus Gummersbach GMBH	Gummersbach	Germany	D-51643
32	St. Barbara Krankenhaus	Halle	Germany	06003
33	Martin Luther Universitaet	Halle	Germany	06097
34	Altonaer Kinderkrankenhaus	Hamburg	Germany	22763
35	Universitaets-Krankenhaus Eppendorf	Hamburg	Germany	D-20246
36	Evangelische Krankenhaus Hamm	Hamm	Germany	DOH-59063
37	Kinderkrankenhaus auf der Bult	Hannover	Germany	30173
38	Medizinische Hochschule Hannover	Hannover	Germany	D-30625
39	Universitaets-Kinderklinik Heidelberg	Heidelberg	Germany	D-69120
40	Gemeinschaftskrankenhaus	Herdecke	Germany	58313
41	Universitatsklinik Homburg	Homburg	Germany	66421
42	Marien Hospital	Homburg	Germany	D-66421
43	Praxis am Evangelischen Krankenhaus Bethanien	Iserlohn	Germany	D-58644
44	Universitaets - Kinderklinik	Jena	Germany	D-07745
45	Westpfalz-Klinikum GmbH	Kaiserslautern	Germany	D-67653
46	Stadt. Kinderklinik	Karlsruhe	Germany	76131
47	Kinderkrankenhaus	Kassel	Germany	34121
48	Klinikum Kassel	Kassel	Germany	D-34125
49	Staedtische Krankenhaus Kiel	Kiel	Germany	23116
50	University Hospital Schleswig-Holstein - Kiel Campus	Kiel	Germany	D-24105
51	Stadt. Krankenhaus Kemperhof	Koblenz	Germany	56065
52	Staedtisches Kinderkrankenhaus	Koln - Riehl	Germany	D-50735
53	Klinik Konstanz	Konstanz	Germany	78461
54	Klinikum Krefeld GmbH	Krefeld	Germany	D-47805
55	Universitaets - Kinderklinik	Leipzig	Germany	04317
56	Universitaets Klinik fuer Kinderchirurgie	Leipzig	Germany	D-04317
57	Universitaets - Kinderklinik - Luebeck	Lubeck	Germany	23538
58	St. Annastift Krankenhaus	Ludwigshafen	Germany	67065
59	Universitatsklinikum der MA	Magdeburg	Germany	39112
60	Johannes Gutenberg University	Mainz	Germany	D-55131
61	Stadt. Klinik - Kinderklinik	Mannheim	Germany	68167
62	Universitaets - Kinderklinik	Marburg	Germany	35033
63	Klinikum Minden	Minden	Germany	D-32423
64	Klinik und Poliklinik fuer Kinderheilkunde - Universitaetsklinikum Muenster	Muenster	Germany	D-48149
65	Universitaets - Kinderpoliklinik	Munich	Germany	80336
66	Kinderklinik d. TU / Schwabing	Munich	Germany	80804
67	Staedtisches Krankenhaus Muenchen - Harlaching	Munich	Germany	D-81545
68	Kinderklinik	Munich	Germany	DOH-80337
69	Kinderklinik Kohlhof	Neunkirchen	Germany	66539
70	Cnopfche Kinderklinik	Nuernberg	Germany	90419
71	Klinikum Oldenburg	Oldenburg	Germany	26133
72	Kindershospital	Osnabruck	Germany	D-49082
73	Krankenhaus D Barmherzigen Brueder	Regensburg	Germany	93049
74	Staedtische Klinikum-Kinderklinik	Rosenheim	Germany	83022
75	Kinderklinik - Universitaetsklinikum Rostock	Rostock	Germany	D-18057
76	Saarbrucker Winterbergkliniken	Saarbrucken	Germany	66119
77	Diakone - Krankenhaus	Schwabisch Hall	Germany	74523
78	Klinikum Schwerin	Schwerin	Germany	D-19049
79	Leopoldina - Krankenhaus	Schwienfurt	Germany	97422
80	Deutsches Rotes Kreuz	Siegen	Germany	57072
81	Johanniter-Kinderklinik	St. Augustin	Germany	53757
82	Olgahospital	Stuttgart	Germany	DOH-70176
83	Mutterhaus der Borromaerinnen	Trier	Germany	D-54290
84	Universitaetsklinikum Tuebingen	Tuebingen	Germany	D-72076
85	Universitaet Ulm	Ulm	Germany	D-89075
86	St. Marien Hospital	Vechta	Germany	D-49377
87	Reinhard - Nieter - Krankenhaus	Wilhelmshaven	Germany	26389
88	Universitaets - Kinderklinik Wuerzburg	Wuerzburg	Germany	D-97080
89	Helios Klinikum Wuppertal	Wuppertal	Germany	D-42283
90	Academisch Ziekenhuis Maastricht	Maastricht	Netherlands	6202 AZ
91	University Children's Hospital	Basel	Switzerland	CH-4005
92	Ospedale "la Carita", Locarno	Locarno	Switzerland	6600
93	Kinderspital Luzerne	Luzerne 16	Switzerland	CH-6000
94	University Children's Hospital	Zurich	Switzerland	CH-8032