A Phase II Study Evaluating the Efficacy and Safety of Ultratrace Iobenguane I 131 in Patients With Malignant Relapsed/Refractory Pheochromocytoma/Paraganglioma
Phase: PHASE2
Conditions: Pheochromocytoma, Paraganglioma
Sponsor: Molecular Insight Pharmaceuticals, Inc.

NCT00874614

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1. TABLE OF CONTENTS
1. TABLE OF CONTENTS ........................................................................................................................................ 1 
2. PROTOCOL APPROVAL ..................................................................................................................................... 5 
3. ABBREVIATIONS.................................................................................................................................................. 6 
4. STUDY OUTLINE .................................................................................................................................................. 9 
5. TITLE OF STUDY................................................................................................................................................17 
6. PROTOCOL AND EUDRACT NUMBER .........................................................................................................17 
7. INTRODUCTION .................................................................................................................................................17 
7.10$/,*1$173+(2&+5202&<720$3$5$*$1*/,20$ 
7.2&$55,(5$''(',2%(1*8$1(, 
7.312&$55,(5$''('8/75$75$&(,2%(1*8$1(,'26,1*5(*,0(1 
7.4%,20$5.(56)253+(2&+5202&<720$$1'3$5$*$1*/,20$ 
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8. STUDY OBJECTIVE............................................................................................................................................28 
9. INVESTIGATIONAL PLAN ...............................................................................................................................28 
9.1678'<'(6,*1 
9.2678'<'(6,*15$7,21$/( 
9.3678'<'85$7,21 
9.4678'<3238/$7,21 
9.5,1&/86,21&5,7(5,$ 
9.6(;&/86,21&5,7(5,$ 
9.7',6&217,18$7,21&5,7(5,$ 
9.89,6,76)25',6&217,18('68%-(&76127:,7+'5$:,1*&216(17 
10. STUDY AGENT ..................................................................................................................................................35 
10.1'26,1*(9$/8$7,216 
10.2'26(02',),&$7,21 
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'RVHPRGLILFDWLRQIRUKHPDWRORJLFWR[LFLW\ 
10.3678'<$*(17'(6&5,37,21 
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10.45(&(,37$1'6725$*(2)'58*352'8&7 
10.5%/,1',1*$1'5$1'20,=$7,21 
10.6+$1'/,1*$1'35(3$5$7,21 

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10.7$'0,1,675$7,21 
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10.9$&&2817$%,/,7< 
11. METHODOLOGY ..............................................................................................................................................40 
11.1:5,77(1,1)250('&216(17$66(17 
11.268%-(&7180%(5,1* 
11.36&5((1,1*%$6(/,1( 
11.4(9$/8$7,212)$17,+<3(57(16,9(67$786 
11.568%-(&7(9$/8$7,216 
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8OWUDWUDFHLREHQJXDQH,6FDQV 
/RQJ7HUP)ROORZ8S 
$VVHVVPHQW:LQGRZV 
11.6(/,*,%,/,7<'26,0(75<6&$16 
$VVHVVPHQWRI%LRGLVWULEXWLRQRI8OWUDWUDFH,REHQJXDQH, 
,PDJH$FTXLVLWLRQ 
,PDJH$VVHVVPHQW 
'RVLPHWU\ 
11.7&72505,0$*((9$/8$7,21 
12. REPORTING SAFETY INFORMATION........................................................................................................54 
12.1$'9(56((9(176 
'HILQLWLRQV 
5HSRUWLQJ6HULRXV$GYHUVH(YHQWV 
 
5HSRUWLQJ$GYHUVH(YHQWVRI6SHFLDO,QWHUHVW 
%UHDNLQJWKH6WXG\%OLQG 
'DWD&ROOHFWLRQ 
6XEMHFW)ROORZXS 
12.2/$%25$725<(9$/8$7,216 
5HSRUWLQJDQG(YDOXDWLRQRI/RFDO/DERUDWRU\7HVW5HVXOWV 
$GGLWLRQDOSURFHGXUHVE\VLWH 
5HSHDW7HVWLQJ 
12.3(/(&752&$5',2*5$0(9$/8$7,21 
12.43+<6,&$/(;$0,1$7,216 
12.59,7$/6,*16 
13. STATISTICAL METHODS...............................................................................................................................59 
13.1$1$/<6,66(76 
13.26$03/(6,=( 
13.367$7,67,&$/0(7+2'6 
'HVFULSWLYHDQGVXPPDU\VWDWLVWLFV 

8OWUDWUDFH,REHQJXDQH,
3KHRFKURPRF\WRPD
3URWRFRO1R0,3,%%
3DJH

0,3,%%B&63B9DB0DU

&21),'(17,$/
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(IILFDF\$QDO\VLV 
 
3ULPDU\$QDO\VLV5HGXFWLRQLQXVHRIDQWLK\SHUWHQVLYHPHGLFDWLRQ 
 
6HFRQGDU\$QDO\VHV 
 
2YHUDOO7XPRU5HVSRQVHSHU5(&,67&ULWHULD 
 
7XPRU0DUNHU5HVSRQVH3URSRUWLRQ 
 
%RQH/HVLRQ6WDWXV 
 
4XDOLW\RI/LIH4R/ 
 
6\PSWRP5HVSRQVH 
 
$QDOJHVLFVDQGSDLQPHGLFLQH 
 
.DUQRIVN\3HUIRUPDQFH6WDWXV 
 
2YHUDOOVXUYLYDO26 
 
9LDEOHWXPRUWLVVXHH[SORUDWRU\ 
6DIHW\$QDO\VLV 
 
6DIHW\,QGLFDWRUV 
 
'RVLPHWU\ 
13.4352&('85(6)25+$1'/,1*0,66,1*8186('$1'6385,286'$7$ 
13.5352&('85(6)255(3257,1*'(9,$7,2167225,*,1$/67$7,67,&$/$1$/<6,63/$1 
13.6'$7$021,725,1*&200,77(('0& 
14. ETHICS................................................................................................................................................................67 
14.1(7+,&$/&216,'(5$7,216 
14.2,1)250('&216(17$66(17 
14.3,167,787,21$/5(9,(:%2$5',1'(3(1'(17(7+,&6&200,77(($33529$/ 
15. ADMINISTRATIVE CONSIDERATIONS ......................................................................................................68 
15.15(*8/$725<5(48,5(0(176±6321625,19(67,*$7252%/,*$7,216 
15.235272&2/$0(1'0(176 
15.3&855,&8/809,7$( 
15.4$'0,1,675$7,9(6758&785( 
15.5021,725,1*352&('85(6 
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16. CONFIDENTIALITY .........................................................................................................................................71 
17. INVESTIGATOR STATEMENT ......................................................................................................................72 
18. REFERENCES ....................................................................................................................................................73 
19. APPENDICES......................................................................................................................................................77 
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5. TITLE OF STUDY
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7.2 Carrier-Added Iobenguane I 131
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TABLE 1: SUMMARY OF CARRIER-ADDED IOBENGUANE I 131 THERAPY FOR 156 MALIGNANT 
PHEOCHROMOCYTOMA PATIENTS
Study
N 
Tx type
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9. INVESTIGATIONAL PLAN
9.1 Study Design
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9.6 Exclusion Criteria
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9.7 Discontinuation Criteria
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10. STUDY AGENT
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TABLE 2:  LABORATORY ANALYTES 
Hematology
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TABLE 3: BLOOD PRESSURE MEASUREMENTS
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Screening
/Baseline
First 6 weeks 
following 
therapeutic 
dose(s) (dose 1 
and dose 2)
Through week 
24 ( at weeks 
when not 
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weekly)
Months 7-
12
Site staff or visiting nursea 
(blood pressure and heart rate)
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Reporting Adverse Events of Special Interest
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12.2.3 Repeat Testing
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12.3 Electrocardiogram evaluation 
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12.4 Physical Examinations 
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12.5 Vital Signs
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13. STATISTICAL METHODS 
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13.1 Analysis Sets 
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FIGURE 2:  SCHEMATIC OF PROTOCOL DEFINED POPULATIONS
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13.2 Sample Size
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13.3 Statistical Methods
13.3.1 Descriptive and summary statistics
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13.3.2 Efficacy Analysis 
13.3.2.1
Primary Analysis: Reduction in use of antihypertensive medication
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13.3.2.2
Secondary Analyses   
13.3.2.2.1
Overall Tumor Response per RECIST Criteria 
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13.3.3.1
Safety Indicators 
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15.1 Regulatory Requirements–Sponsor/Investigator Obligations 
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18. REFERENCES
 5RPDQ6DQG8GHOVPDQ5(QGRFULQH7XPRUV,Q3ROORFN5(HGUICC Manual of 
Clinical Oncology, Eighth Edition.-RKQ:LOH\DQG6RQV,QF+RERNHQ1-
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 $YHUEXFK6'6WHDNOH\&6<RXQJ5&HWDO0DOLJQDQWSKHRFKURPRF\WRPDHIIHFWLYH
WUHDWPHQW ZLWK D FRPELQDWLRQ RI F\FORSKRVSKDPLGH YLQFULVWLQH DQG GDFDUED]LQH Ann 
Intern Med.$XJ
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19. APPENDICES
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APPENDIX I
KARNOFSKY PERFORMANCE STATUS
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KARNOFSKY PERFORMANCE STATUS
No symptoms, fully active, able to work.
100
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90
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80
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70
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60
Requires considerable assistance and frequent medical care.
50
Disabled; requires special care and assistance.
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30
Very ill; hospitalization necessary; active supportive treatment required.
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Moribund, fatal processes progressing rapidly.
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APPENDIX II
SOLOWAY SCALE FOR EXTENT OF DISEASE IN THE BONE
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APPENDIX III (continued)
EXCLUDED MEDICATIONS DUE TO DRUG INTERACTIONS WITH ULTRATRACE I-
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APPENDIX III (continued)
EXCLUDED MEDICATIONS DUE TO DRUG INTERACTIONS WITH ULTRATRACE I-
131-MIBG
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APPENDIX IV
QUALITY OF LIFE AND SYMPTOMS QUESTIONNAIRES
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NIH Quality of Life and Symptoms Questionnaire for Pheochromocytoma and 
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APPENDIX V
LISTING OF ANALGESICS, PAIN AND ANTIHYPERTENSIVE MEDICATIONS
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