ENRICH: Whole Brain Radiation Therapy With Oxygen, With or Without RSR13, in Women With Brain Metastases From Breast Cancer

Sponsor

Spectrum Pharmaceuticals, Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT00083304

Collaborator

(none)

368

Enrollment

Locations

Arms

Duration (Months)

3.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RSR13 (efaproxiral) is a radiation sensitizer that has shown positive results in a Phase 3, randomized clinical trial of patients with brain metastases. Of 111 eligible breast cancer patients with brain metastases in that trial, 59 patients who received RSR13 prior to radiation therapy had a median survival time that was twice as long as the 52 patients who did not receive RSR13 prior to radiation therapy.

RSR13 (efaproxiral) is an experimental drug that increases the amount of oxygen released from blood into the tissues. It is well known that certain types of cancer tumors, including those in brain metastases, lack oxygen. Lack of oxygen in a tumor can reduce the effect of radiation therapy (RT). RSR13 may increase the oxygen level in brain tumors so that radiation therapy works better.

This study will enroll up to 360 women with brain metastases from breast cancer, and will evaluate if whole brain radiation therapy given with RSR13 will have a better treatment effect than whole brain radiation therapy alone. RSR13 will be infused intravenously (IV) through a central catheter placed in a central vein. Women randomized (assigned) to receive RSR13, therefore, will need to have a central catheter placed for treatment unless one is already in place.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Metastases	Drug: Efaproxiral Radiation: Whole Brain Radiation Therapy (WBRT) Other: Supplemental Oxygen	Phase 3

Detailed Description

The screening process will include documentation of the cancer, which which will require a brain scan and may include a liver scan. Other screening measurements will include a Karnofsky Performance Status (KPS) assessment, measurement of the amount of oxygen in the blood, using a non-invasive device most often placed on the finger, lung function tests that will require blowing into a machine, and an electrocardiogram (ECG). About 2 teaspoons, or 10 mL, of blood will be taken for specific laboratory tests, and a pregnancy test will be done on the blood of women of childbearing potential.

All study patients will receive supplemental oxygen and whole brain radiation therapy (WBRT) (30 Gy, 3 Gy fractions) every weekday for 2 weeks. Half of the patients will be randomized (assigned) to receive RSR13 prior to WBRT, and will need to have a central catheter placed for treatment unless one is already in place. Patients who receive RSR13 will also need to continue to receive oxygen in the clinic until the amount of oxygen in their blood is near normal. This level has returned to near normal in most patients within 1 to 2 hours.

During treatment and follow-up visits, physical and neurological exam, KPS assessment, weight, height, and vital sign measurements, and about 2 teaspoons of blood may be required. Patients will need to return for follow-up visits 1 month after completion of treatment, 2 months later, and every 3 months thereafter until their doctor tells them otherwise.

Study Design

Study Type:

Interventional

Actual Enrollment :

368 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 3 Randomized, Open-label Comparative Study of Standard Whole Brain Radiation Therapy With Supplemental Oxygen, With or Without Concurrent RSR13 (Efaproxiral), in Women With Brain Metastases From Breast Cancer

Study Start Date :

Feb 1, 2004

Actual Primary Completion Date :

Jun 1, 2007

Actual Study Completion Date :

Jun 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Efaproxiral + WBRT + Supplemental Oxygen	Drug: Efaproxiral 75 mg/kg, administered over 30 minutes via a central venous access device (CVAD). Administered 30 minutes prior to the start of whole brain radiation therapy (WBRT) on each WBRT treatment day for 10 days. Other Names: RSR13 Radiation: Whole Brain Radiation Therapy (WBRT) 3.0 Gy per day for 10 days (30.0 Gy total) of WBRT. Other: Supplemental Oxygen 4 L/minute by nasal cannula. Administered at least 35 minutes prior to WBRT, during WBRT and until 15 minutes after completion of WBRT on all WBRT treatment days.
Active Comparator: WBRT + Supplemental Oxygen	Radiation: Whole Brain Radiation Therapy (WBRT) 3.0 Gy per day for 10 days (30.0 Gy total) of WBRT. Other: Supplemental Oxygen 4 L/minute by nasal cannula. Administered at least 35 minutes prior to WBRT, during WBRT and until 15 minutes after completion of WBRT on all WBRT treatment days.

Arm

Intervention/Treatment

Experimental: Efaproxiral + WBRT + Supplemental Oxygen

Drug: Efaproxiral

75 mg/kg, administered over 30 minutes via a central venous access device (CVAD). Administered 30 minutes prior to the start of whole brain radiation therapy (WBRT) on each WBRT treatment day for 10 days.

Other Names:

RSR13

Radiation: Whole Brain Radiation Therapy (WBRT)

3.0 Gy per day for 10 days (30.0 Gy total) of WBRT.

Other: Supplemental Oxygen

4 L/minute by nasal cannula. Administered at least 35 minutes prior to WBRT, during WBRT and until 15 minutes after completion of WBRT on all WBRT treatment days.

Active Comparator: WBRT + Supplemental Oxygen

Radiation: Whole Brain Radiation Therapy (WBRT)

3.0 Gy per day for 10 days (30.0 Gy total) of WBRT.

Other: Supplemental Oxygen

4 L/minute by nasal cannula. Administered at least 35 minutes prior to WBRT, during WBRT and until 15 minutes after completion of WBRT on all WBRT treatment days.

Outcome Measures

Primary Outcome Measures

Overall Survival [Measured from randomization until death due to any cause.]

Secondary Outcome Measures

Response Rate in the Brain at 3 Months [Assessed at screening, 3 months after end of study treatment and at least 4 weeks after the 3-month scan.]
Karnofsky Performance Status & Neurological Signs & Symptoms [Assessed at baseline, 1 month follow-up (FU) visit, 3 month FU visit, and 6 month FU visit.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult women with brain metastases from breast cancer
Minimum KPS of 70

Exclusion Criteria:

Previous treatment for brain metastases, including brain surgery and any form of radiation to the brain

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Virginia G. Piper Cancer Center, Arizona Oncology Services	Phoenix	Arizona	United States	85013
2	Arizona Cancer Center, University of Arizona	Tucson	Arizona	United States	85724-5081
3	The University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Alta Bates Comprehensive Cancer Center	Berkeley	California	United States	94704
5	University of California at Los Angeles	Los Angeles	California	United States	90095
6	Radiological Associates of Sacramento	Sacramento	California	United States	95816
7	UCSF - Comprehensive Cancer Center	San Francisco	California	United States	94115
8	Yale University School of Medicine	New Haven	Connecticut	United States	06520
9	Boca Raton Community Hospital	Boca Raton	Florida	United States	33486
10	University of Miami Medical	Miami	Florida	United States	33136
11	University of South Florida - H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
12	Emory University Winship Cancer Institute	Atlanta	Georgia	United States	30322
13	Northwestern University	Chicago	Illinois	United States	60611
14	Parkview Research Center	Ft. Wayne	Indiana	United States	46805
15	Indiana University School of Medicine	Indianapolis	Indiana	United States	46204
16	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
17	Johns Hopkins Oncology Center	Baltimore	Maryland	United States	21231
18	Maryland Hematology Oncology	Baltimore	Maryland	United States	21236
19	Franklin Square Hospital Center	Baltimore	Maryland	United States	21237
20	Center for Cancer and Blood Disorders	Bethesda	Maryland	United States	20817
21	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
22	Henry Ford Hospital	Detroit	Michigan	United States	48202
23	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
24	Washington University School of Medicine	St. Louis	Missouri	United States	63110
25	Dent Neurologic Institute	Amherst	New York	United States	14226
26	Eastchester Center for Cancer Care	Bronx	New York	United States	10469
27	SUNY Downstate Medical Center	Brooklyn	New York	United States	11203
28	University of North Carolina Breast Center	Chapel Hill	North Carolina	United States	27599
29	Duke University Medical Center	Durham	North Carolina	United States	27710
30	University of Cincinnati Division of Hematology-Oncology	Cincinnati	Ohio	United States	45267
31	Cleveland Clinic Hospital	Cleveland	Ohio	United States	44195
32	Ohio State University	Columbus	Ohio	United States	43210
33	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
34	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
35	Texas Oncology	Dallas	Texas	United States	75230
36	Texas Oncology	Fort Worth	Texas	United States	76104
37	Virginia Mason Cancer Center	Seattle	Washington	United States	98101
38	Wenatchee Valley Clinic	Wenatchee	Washington	United States	98801
39	University of Wisconsin	Madison	Wisconsin	United States	53792
40	Instituto Medico Especializado Alexander Fleming	Buenos Aires	Cuidad de Buenos Aires	Argentina	C1426ANZ
41	Instituto de Oncologia A. Roffo	Buenos Aires		Argentina	CP 1417
42	Hospital Espanol	Buenos Aires		Argentina	CP C1209
43	Instituto Privado de Radioterapia y Oncologia	Cordoba		Argentina	CP 5000
44	Centro de Terapia Radiante Cumbres (CAICI)	Rosario		Argentina	2000
45	LKH-Universitatsklinikum Graz	Graz		Austria	A-8036
46	Medical University Innsbruck	Innsbruck		Austria	6020
47	Hospital Sao Lucas PUC	Teofilo	Fortaleza Ceara	Brazil	60430-230
48	Fundação Pio XII - Hospital do Câncer de Barretos	Barretos	SP	Brazil	14780-400
49	Hospital Erasto Gaertner	Curitiba		Brazil	81520-060
50	Velindre Hospital	Porto Alegre		Brazil	90610-000
51	Hospital Santa Rita da Irmandade da Santa Casa	Porto Alegre		Brazil	CEP 90020-090
52	Instituto Brasileiro de Controle do Cancer	Sao Paulo		Brazil	CEP 03102-002
53	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
54	Cross Cancer Center	Edmonton	Alberta	Canada	T6G 1Z2
55	Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
56	Ottawa Regional Cancer Centre	Ottawa	Ontario	Canada	K1H 1C4
57	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
58	Hopital Maisonneuve-Rosemont	Montreal	Quebec	Canada	H1T 2M4
59	CHUM - Campus Notre Dame	Montreal	Quebec	Canada	H2L 4M1
60	McGill University	Montreal	Quebec	Canada	H2W 1S6
61	Hotel-Dieu de Quebec du CHUQ	Quebec City	Quebec	Canada	G1R 5C3
62	Centre Hospitalier Universitarie de Service de Radio-Oncologie	Sherbrooke	Quebec	Canada	J1H 5N4
63	Cilnica Santa Maria	Providencia	Santiago de Chile	Chile
64	Clinical Hospital Osijek	Osijek		Croatia	4
65	CHU Zagreb University School of Medicine	Zagreb		Croatia	10000
66	University Hospital for Tumors	Zagreb		Croatia	197
67	Centre Georges François Leclerc	Dijon Cedex		France	21079
68	Centre Oscar Lambret	Lille Cedex		France	59020
69	Centre Léon Bérard	Lyon Cedex		France	69373
70	Hopital de Montbeliard	Montbeliard		France	25209
71	Centre Antioned Lacasagne	Nice		France	06 189
72	Centre Hospitalier Lyon Sud	Pierre-Benite		France	69310
73	CHU Poitiers	Poitiers		France	86021
74	Centre Rene Huguenin	Saint-Cloud		France	92210
75	Clinique Armoricaine de	St. Brieuc		France	22015
76	Institut Gustave Roussy	Villejuif Cedex		France	94 805
77	Hygeia Diagnostic and Therapeutic Center of Athens	Athens		Greece	151 23
78	University of Debrecen	Debrecen	Hajdú-Bihar	Hungary	4032
79	University of Szeged	Szeged		Hungary	H-6720
80	Azienda Ospedaliera Maggiore della Carita	Novara		Italy	28100
81	Ospedale S Chiara, University of Pisa	Pisa		Italy	56100
82	Kaunas Medical University Hospital	Kaunas		Lithuania	50009
83	Institute of Oncology, Vilnius University	Vilnius		Lithuania	LT-086660
84	Hospital Edgardo Rebagliati Martins (ESSALUD)	Lima		Peru	11
85	Radiooncologia, Radiation Oncology Center	Lima		Peru	27
86	Instituto de Enfermedades Neoplasicas (INEN)	Lima		Peru	34
87	Instituto Catalan de Oncologia (ICO)	Barcelona		Spain	08907
88	Ciutat Sanitari de Vall d'Hebron	Barcelona		Spain	8035
89	Hospital Ramon Y Cajal	Madrid		Spain	28034
90	Clinica Universitaria de Navarra	Pamplona		Spain	31008
91	Instituto Valenciano de Oncologia	Valencia		Spain	46009
92	Velindre Hospital	Whitchurch	Cardiff	United Kingdom	CF14 2TL
93	Royal Sussex County Hospital	Brighton		United Kingdom	BN2 5BE
94	Beatson Oncolgy Center	Glasgow		United Kingdom	G11 6NT