Compound
(common name)
[Company] / Structure / IC50 (nM)
RTK1 / RTK2 / RTK3 / Non-RTK / Ser/Thr
EGFR / IGF-1R / KIT / Flt-3 / C-fms / Src / Abl / B-Raf / p38
AAL881
[Novartis] / / >1000 / >1000 / 0.96 / 0.94
AAL993
[Novartis] / / 10,400 / >10,000 / 380 / >10,000 / 2820
AEE788
[Novartis] / / 2 / >10 / 780 / 61 / 52 / 2800
ABT-869
[Abbott] / / >50,000 / >50,000 / 14 / 4 / >50,000
AG-013736
(axitinib)
[Pfizer] / / 2 / >1000
AMG 706
(motesanib)
[Amgen] / / >3000 / >3000 / >3000
AZD2171
(cediranib)
[AstraZeneca] / / 1630 / >1000 / 113 / 128 / 258
ZD4190
[AstraZeneca] / / 400
ZD6474
(vandetanib)
[AstraZeneca] / / 500 / >200,000 / >20,000
BAY 43-9006
(sorafenib)
[Bayer] / / >10,000 / >10,000 / 68 / 58 / 22 / 36
BAY 57-9352
(telatinib)
[Bayer] /
BIBF 1120
[Boehringer] / / >50,000 / >10,000 / 26 / 156
BMS -540215
[Bristol Myers] / / >1900
BMS-582664
(brivanib alaninate)
[Bristol Myers] / / Prodrug of BMS-540215 -- see above
BMS-605541
[Bristol Myers] / / >25,000 / >10,000 / >5000
BMS-645737
[Bristol Myers] / / 150
CEP-7055
[Cephalom/Sanofi] / / 57 / 1.6 / >10,000
CHIR-258 (TKI258)
[Chiron] / NO STRUCTURE PROVIDED / 2 / 2 / 1
CP-547,632
[Pfizer] / / 6250 / >10,000
E7080
[Eisai] / / 6500 / >10,000 / >10,000
GW654652
[GSK] / / 1360 / 530 / 350
GW786034
(pazopanib)
[GSK] / / >20,000 / >8000 / 74 / >10,000 / 146 / 3090 / 2000 / >25,000 / 2056
KRN633
[Kirin] / / >10,000 / 8
KRN951
[Kirin] / / 1.63 / 422
OSI-930
[OSI] / / >10,000 / 15-629 / 1303 / 4738 / 41
PD 173074
[Warner-Lambert] / / >50,000 / >10,000
PF-00337210
[Pfizer]* / NO STRUCTURE PROVIDED / 9.6 / >10,000
PTK787/ZK 222584
(vatalanib)
[Novartis] / / >10,000 / >10,000 / 730 / 1400 / >10,000 / >10,000 / >20,000
SU1498
[Sugen] / / >100
SU5416
(semaxinib)
[Sugen] / / >100,000 / >20,000 / 32
SU5614
[Sugen] / / >100,000 / 6700 / 28
SU6668
[Sugen] / / >100,000 / >28,000 / 10.5
SU11248
(sunitinib)
[Sugen] / / >20,000
SU11657
[Sugen] / NO STRUCTURE PROVIDED / >20,000
SU14813
[Sugen] / / >20,000 / 15 / 2500
TKI-28
[?] / / 21 / 46 / 11
TKI-31
[?] / / >100,000 / 167 / 90
ZM323881
[AstraZeneca] / / >50,000
*Information in abstract form only: Marrone et al. 2007 Proc Am Assoc Cancer Res. Abstract 3992
supplementary Table 2. Multitargeted small molecule receptor tyrosine kinase inhibitorsCompound
(common name)
[Company] / Structure / IC50 (nM)
RTK4 / RTK3 / RTK1 / RTK10
VEGFR-1 / VEGFR-2 / VEGFR-3 / PDGFR / PDGFR / FGFR / Tie2
AAL881
[Novartis]61 / / 0.25 / >1000
AAL993
[Novartis]62 / / 130 / 23 / 18 / 640 / 10,400 / >10,000
AEE788
[Novartis]63 / / 59 / 77 / 330 / 320
ABT-869
[Abbott]64 / / 3 / 4 / 190 / 66 / >12,500 / 170
AG-013736
(axitinib)
[Pfizer]65, 66 / / ~0.1 / 0.2 / 0.1-0.3 / 5 / 1.6
AMG 706
(motesanib)
[Amgen]67 / / 2 / 3 / 6 / 84
AZD2171
(cediranib)
[AstraZeneca]68 / / 5 / <2 / <2 / 36 / 5 / 26 / >1000
ZD4190
[AstraZeneca]69, 70 / / 708 / 29 / 5300
ZD6474
(vandetanib)
[AstraZeneca]69, 71 / / 1600 / 40 / 110 / >1000 / 3600
BAY 43-9006
(sorafenib)
[Bayer]72 / / 90 / 20 / 57 / 580
BAY 57-9352
(telatinib)
[Bayer]73 / / 6 / 4 / 15
BIBF 1120
[Boehringer]77 / / 34 / 21 / 13 / 59 / 65 / 69
BMS -540215
[Bristol Myers]78, 79 / / 380 / 25 / >6000 / 148
BMS-582664
(brivanib alaninate)
[Bristol Myers] / / Prodrug of BMS-540215 -- see above
BMS-605541
[Bristol Myers]80 / / 400 / 23 / 200 / >5000
BMS-645737
[Bristol Myers]81 / / 268 / 25 / >2000 / 78
CEP-7055
[Cephalon/
Sanofi]82 / / 18 / 8 / 4 / 406 / 162 / >10,000
CHIR-258 (TKI258)
[Chiron]83 / NO STRUCTURE PROVIDED / 10 / 13 / 8 / 210 / 27 / 8 / 4
CP-547,632
[Pfizer]84 / / 11 / 2850 / 9 / 48
E7080
[Eisai]85 / / 22 / 4 / 5.2 / 51 / 39
GW654652
[GSK]86 / / 12 / 2.3 / 2.5 / 320
GW786034
(pazopanib)
[GSK]87-89 / / 10 / 30 / 47 / 71 / 84 / 140 / 4520
KRN633
[Kirin]90 / / 11.7 / 1.16 / 130 / >10,000
KRN951
[Kirin]91 / / 0.21 / 0.16 / 0.24 / 1.72 / 299
OSI-930
[OSI]92 / / 8 / 9 / 3408 / 6900 / >10,000
PD 173074
[Warner-Lambert]93 / / 100-200 / 21.5
PF-00337210
[Pfizer]* / NO STRUCTURE PROVIDED / 0.87 / 0.7 / 11 / 29
PTK787/ZK 222584
(vatalanib)
[Novartis]94, 95 / / 77 / 37 / 640 / >10,000 / 580-2300 / >10,000 / >10,000
RO0281501
[Hoffmann-
La Roche]96 /
SU1498
[Sugen]97 / / 0.7 / >50 / >50
SU5416
(semaxinib)
[Sugen]98, 99 / / 1000 / >20,000 / >40,000
SU5614
[Sugen]99, 100 / / 500 / 130 / 3100
SU6668
[Sugen]101 / / 3900 / 100 / 3800
SU11248
(sunitinib)
[Sugen] 102, 103 / / 9 / 8 / 830
SU11657
[Sugen]104 / NO STRUCTURE PROVIDED / 10 / 1
SU14813
[Sugen]105 / / 2 / 50 / 4 / 3500
TKI-28
[?]106 / / >1000 / 27 / 36
TKI-31
[?]107 / / >100,000 / 596 / 304
YM-231146
[Yamanouchi]108 / / 80
YM-359445
[Yamanouchi]109 / / 8.5
XL647
[Exelixis]**110 / NO STURCTURE OR INFORMATION PROVIDED
XL880
[Exelixis]
(GSK 1363089)
[GSK]# / NO STURCTURE OR INFORMATION PROVIDED
XL999† / NO STURCTURE OR INFORMATION PROVIDED
ZM323881
[AstraZeneca]111 / / >50,000 / 2 / >50,000 / >50,000
*Information in abstract form only: Marrone et al. 2007 Proc Am Assoc Cancer Res. Abstract 3992
**Information in abstract form only: Wakelee et al., 2006 Proc Am Soc Clin Oncol. Abstract 3044.
#Information in abstract form only: Eder et al., 2006 Proc Am Soc Clin Oncol. Abstract 3041; LoRusso et al., 2006 Eur J Cancer (Suppl 4), Abstract 404; Eder et al., 2007 Proc Am Soc Clin Oncol. Abstract 3526..
†Information in abstract form only: Mita et al. 2006 Eur J Cancer (Suppl 4) Abstract 83; Cooper et al., 2006 Proc Am Soc Clin Oncol. Abstract 13024; Cripe et al. 2007 Proc Am Soc Clin Oncol. 3591; March et al. 2007 Proc Am Soc Clin Oncol. Abstract 18112.
1
supplementary table 3. Phase 3 clinical trials of vegf receptor tyrosine kinase inhibitorsAgent / Trial / Disease / Status
(January 2009) / Other Agent(s)* / Design / Endpoint(s) / Projected or Final Accrual
axitinib / NCT00678392: Axitinib (AG 013736) as second line therapy for metastatic renal cell cancer / RCC / AC / (sorafenib) / randomized open label
Arm A
axitinib 5 mg BID continuous
Arm B
sorafenib 400 mg BID continuous / 1°: PFS
2°: OS, RR, safety, tolerability, DR / 540
NCT00471146:
Study of gemcitabine plus AG-013736 versus gemcitabine for advanced pancreatic cancer / pancreatic cancer / AC / gemcitabine / randomized double blind
Arm A
axitinib 5 mg BID daily + gemcitabine1000 mg/m2 IV days 1, 8, 15 q 4 weeks
Arm Bgemcitabine as in Arm A / 1°: OS
2°: ORR, safety and tolerability DR, QOL, population PK, PFS / 596
cediranib / NCT00399035:
Cediranib (AZD2171, RECENTIN™) in addition to chemotherapy in patients with untreated metastatic colorectal cancer (HORIZON II) / CRC / CL / FOLFOX
XELOX / randomized double blind
Arm 1
FOLFOX regimen
(5-fluorouracil, leucovorin, oxaliplatin)
Arm 2
XELOXregimen
(capecitabine 1000 mg/m2 PO BID days 1-15; oxaliplatin 130 mg/m2 IV day 1, oxaliplatin)
Arm 3
cediranib + FOLFOX
Arm 4
cediranib + XELOX / 1°: efficacy vs. FOLFOX or XELOX
2°: ORR, safety, rate of liver resection, incidence of wound healing complications / 1050
NCT00384176:
First line metastatic colorectal cancer therapy in combination with FOLFOX (HORIZON III) / AC / FOLFOX
(bevacizumab) / randomized double blind
Arm 1
bevacizumab + FOLFOX
Arm 2
cediranib + FOLFOX / 1°: efficacy of cediranib + FOLFOX vs bevacizumab + FOLFOX
2°: OS, overall RR, safety, tolerability, QOL / 1600
cediranib / NCT00777153:
Phase III: Cediranib in combination with lomustine chemotherapy in recurrent glioblastoma (REGAL) / glioblastoma / AC / lomustine / randomized double blind
Arm A
cediranib 30 mg PO daily
Arm B
cediranib 20 mg PO daily + lomustine 110 mg/m2 PO q 6 weeks
Arm C
lomustine 110 mg/m2 PO q 6 weeks / 1°: PFS
2°: OS, APF6, overall RR, safety, tolerability, QOL / 300
cediranib / NCT00795340:
Cediranib, paclitaxel, and carboplatin in treating patients with stage IIIB or stage IV non-small cell lung cancer / NSCLC / NO / carboplatin +
paclitaxel / randomized double blind
Arm I
cediranib PO daily days 1-21, paclitaxel IV + carboplatin IV, day 1
Arm II
placebo PO daily days 1-21 + paclitaxel IV and carboplatin IV day 1 / 1°: OS
2°: PFS, ORR, DR, TTR / 750
NCT00245154:
Paclitaxel and carboplatin with or without AZD2171 in treating patients with stage III or stage IV non-small cell lung cancer / CL / carboplatin +
paclitaxel / randomized double blind
Arm I
cediranib PO daily continuous + paclitaxel IV and carboplatin IV q 3 weeks
Arm II
placebo + paclitaxel/carboplatin / 1°: PFS
2°: OS, toxicity, QOL, correlatives / 750
NCT00544973:
Carboplatin and paclitxel with or without cediranib in treating women with relapsed ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer / relapsed ovarian epithelial cancer
fallopian tube cancer
primary peritoneal cancer / AC / carboplatin +
paclitaxel / randomized double blind
Arm A
carboplatin IV and paclitaxel IV day 1 + placebo days 1-21
Arm B
cediranib PO daily days 1-21 + paclitaxel/carboplatin day 1 (6 courses); placebo x 60 weeks
Arm C
cediranib PO daily days 1-21 + paclitaxel/carboplatin day 1 (6 courses); cediranib PO daily x 60 weeks / 1°: PFS, OS, safety
2°: toxicity, QOL / 2000
NCT00532194: An RCT of concurrent and maintenance cediranib in women with platinum-sensitive relapsed ovarian cancer (ICON6) / ovarian cancer / NO / Pt-based standard chemo-
therapy / 3-stage, randomized double blind
Arm A
Pt-based chemo + placebo
Arm B
Pt chemo + cediranib 30 mg PO daily during chemo only
Arm C
Pt chemo + cediranib 30 mg PO daily continuous x 18 mo. / 1°: stage 1 - safety; stage 2 - PFS; stage 3 - OS
2°: stage 1 - N/A; stage 2 - OS, toxicity;
stage 3 - PFS, toxicity, QOL / stage 1: 50
stage 2: 600
stage 3: 2000
motesanib / NTC00460317:
AMG 706/placebo in combination with chemotherapy to treat advanced NSCLC / NSCLC / AC / paclitaxel +
carboplatin / randomized double blind
Arm A
paclitaxel 200 mg/m2 + carboplatin AUC=6 day 1 of each 3-week cycle (max. 6 cycles) + placebo
Arm B
motesanib 125 mg PO QD + paclitaxel/carboplatin as above / 1°: OS
2°: PFS, ORR, DR / 1240
pazopanib / NCT00558103:
Pazopanib plus lapatinib compared to lapatinib alone in subjects with inflammatory breast cancer / breast cancer / AC / lapatinib / randomized
Arm 1
lapatinib
Arm II
pazopanib + lapatinib / 1°: PFS
2°: Overall RR, OS, safety, tolerability / 320
NCT00775307:
Adjuvant pazopanib in stage I NSCLC / NSCLC / NO / - / randomized double blind
Arm A
pazopanib 800 mg PO daily x 24 weeks
Arm B
placebo / 1°: DFS
2°: OS, toxicity, QOL / 710
NCT00334282:
GW786034 (pazopanib) in metastatic renal cell carcinoma / RCC / CL / - / randomized double blind
Arm A
pazopanib 800 mg PO daily
Arm B
placebo / 1°: PFS
2°: OS, overall RR, safety, QOL, PK / 400
pazopanib / NCT00387764:
Extension study to VEG105192 to assess pazopanib in patients with advanced/metastatic renal cell cancer / RCC (companion to NCT00334282 above) / AC / - / non-randomized open-label trial for patients progressing on placebo arm of NCT00334282
pazopanib 800 mg PO daily / 1°: toxicity
2°: RR, PFS, OS / 132
NCT00720941:
Pazopanib versus sunitinib in the treatment of locally advanced and/or metastatic renal cell carcinoma / RCC / AC / (sunitinib) / randomized open-label
Arm I
pazopanib 800 mg PO daily
Arm II
sunitinib 37.5 mg PO daily / 1°: PFS
2°: OS, ORR, TTR, DR, QOL, safety / 876
NCT00794521:
Pazopanib in treating patients with metastatic soft tissue sarcoma that has relapsed or not responded to treatment / intestinal cancer
kidney cancer
ovarian cancer
soft tissue sarcoma / AC / - / randomized double blind
Arm I
pazopanib PO daily x 28 days
Arm II
Placebo / 1°: efficacy vs. placebo
2°: NA / 255
pazopanib / NCT00753688:
A randomized double blind phase III trial of pazopanib versus placebo in patients with soft tissue sarcoma whose disease has progressed during or following prior therapy (PALETTE) / soft tissue sarcoma / AC / - / randomized double blind
Arm I
pazopanib PO daily x 28 days
Arm II
Placebo / 1°: efficacy vs. placebo
2°: OS, toxicity / 255
semaxinib / NCT00004252:
Leucovorin and fluorouracil with or without SU5416 in treating patients with metastatic colorectal cancer / CRC / CL / fluorouracil
leucovorin / randomized open-label
Arm I
leucovorin IV and fluorouracil IV q week x 6 weeks
Arm II
SU5416 twice weekly + leucovorin/fluorouracil as above / 1°: OS, TTP, DR, ORR, TTF, QOL, safety, tolerability
2°: NA / 710
semaxinib / NCT00021281:
Combination chemotherapy with or without SU5416 in treating patients with metastatic colorectal cancer / CRC / CL / irinotecan
fluorouracil
leucovorin / randomized open-label
Regimen I (Saltz):
Arm 1A
semaxinib IV days 1,4,8,11,15,18,22,25,29,32,36,39 + irinotecan IV, leucovorin IV, and fluorouracil IV days1,8,15,22
Arm IIA
irinotecan, leucovrin, fluorouracil as above
Regimen II (de Gramont)
Arm IB
semaxinib as in Arm IA + irinotecan IV days 1,15,29; leucovrin and fluorouracil IV days 1,2,15,16,29,30
Arm IIB
irinotecan, leucovorin,fluorouracil as in Arm IB / 1°: comparison of OS, safety, QOL
2°: NA / 1270
sorafenib / NCT00492752: A randomized, double-blinded, placebo-controlled study of sorafenib in patients with advanced hepatocellular carcinoma / HCC / CB / - / randomized double blind
Arm 1
sorafenib 400 mg PO BID
Arm 2
Placebo / 1°: OS
2°: TSP, TTP, overall disease control rate, PRO, overall RR, DR, TTR, PK, correlatives / 271
sorafenib / NCT00105443: A phase III randomized, placebo-controlled study of sorafenib in patients with advanced heptocellular carcinoma / HCC / CB / - / randomized double blind
Arm 1
sorafenib 400 mg PO BID
Arm 2
placebo / 1°: OS, TSP
2°: TTP, disease control rate, PRO / 602
NCT00494299:
Phase III study of BAY 43-9006 in Japanese patients with advanced hepatocellular carcinoma / CB / - / randomized double blind
Arm 1
sorafenib 400 mg PO BID
Arm 2
placebo / 1°: TTP
2°: OS / 414
NCT00692770:
Sorafenib as adjuvant treatment in the prevention of recurrence of hepatocellular carcinoma (STORM) / AC / - / randomized double blind
Arm 1
sorafenib 400 mg PO BID
Arm 2
placebo / 1° Recurrence-free survival
2°: TTR, OS, PRO, correlatives / 1100
NCT00699374:
Study of sunitinib malate versus sorafenib in patients with inoperable liver cancer / See trial information under "sunitinib" below
NCT00449033:
A phase III trial comparing the efficacy of gemcitabine, cisplatin and sorafenib to gemcitabine, cisplatin and placebo in first-line treatment of patients with stage IIIb with effusion and stage IV non-small cell lung cancer (NSCLC) / NSCLC / AC / gemcitabine + cisplatin / randomized double blind
Arm 1
gemcitabine 1250 mg/m2 IV and cisplatin 75 mg/m2 IV + sorafenib 400 mg PO BID
Arm 2
gemcitabine/cisplatin as above + placebo / 1°: PFS
2°: safety, OS, PRO / 350
NCT00558636:
A randomized controlled trial comparing safety and efficacy of carboplatin and paclitaxel plus or minus sorafenib (BAY 43-9006) in chemonaive patients with stage IIIB-IV non-small cell lung cancer (NSCLC) / CP / carboplatin + paclitaxel / randomized double blind
Arm 1
paclitaxel 175 mg/m2 IV and carboplatin IV AUC=6 day1 q 21 d + sorafenib 400 mg PO BID days 2-19
Arm 2
paclitaxel/carboplatin as above + placebo / 1°: PFS
2°: OS, tumor response, DR, disease symptoms, QOL / 300
sorafenib / NCT00110019:
Carboplatin and paclitaxel with or without sorafenib in treating patients with unresectable stage III or stage IV melanoma / melanoma / CB / carboplatin + paclitaxel / randomized double blind
Arm I
paclitaxel IV and carboplatin IV day 1 + sorafenib 400 mg PO BID days 2-19
Arm II
paclitaxel/carboplatin as above + placebo / 1°: OS
2°: PFS, ORR / 800
NCT00111007:
A treatment combination for patients with unresectable stage III or stage IV melanoma / melanoma / CB / carboplatin + paclitaxel / randomized double blind
Arm 1
paclitaxel 225 mg/m2 IV and carboplatin AUC=6 IV d 1 + sorafenib 400 mg PO BID days 2-19
Arm 2
paclitaxel/carboplatin as above + placebo / 1°: PFS
2°: AEs, OS, TTP, DR, change in performance status, QOL / 270
NCT00541021:
Gemcitabine with or without sorafenib in treating patients with locally advanced or metastatic pancreatic cancer / pancreatic cancer / AC / gemcitabine / randomized double blind
Arm 1
sorafenib PO BID + gemcitabine IV q weekly x 7 weeks (course 1), then gemcitabine weekly x 3 weeks, followed by sorafenib BID x 1 week (2 courses)
Arm 2
gemcitabine as above + placebo / 1°: PFS
2°: AEs, RR, OS, clinical benefit, QOL, correlatives / 104
NCT00606866:
MRI study of BAY 43-9006 in metastatic renal cell carcinoma / RCC / CB / - / randomized double blind
Arm I
placebo
Arm II
sorafenib 200 mg PO BID
Arm III
sorafenib 400 mg PO BID / 1°: DCE-MRI determination of "best dose"
2°: predict which patients most likely to experience tumor shrinkage / 57
NCT00492986:
An open-label, non-comparative, phase III study of the Raf-kinase inhibitor BAY 43-9006 as a subsequent to first-line therapy in patients with advanced renal cell carcinoma / CP / - / randomized open-label, uncontrolled
sorafenib 400 mg PO BID / 1°: safety
2°: collection of radiological evaluations / 1164
NCT00478114:
Efficacy and safety of sorafenib in advanced renal cell carcinoma / AC / - / non-randomized open-label, uncontrolled
sorafenib 400 mg PO BID / 1°: efficacy (TTP, PFS)
2°: safety / 15
sorafenib / NCT00586105:
Phase III study of sorafenib in patients with RCC / RCC / CP / - / non-randomized open label, uncontrolled
sorafenib 400 mg PO BID / 1°: PK, safety
2°: PFS, OS, TTP, DCR, overall best response, DR, QOL / 40
NCT00732914:
Sequential study to treat renal carcinoma / NO / sunitinib / randomized open label
Arm 1
sunitinib 50 mg PO daily on schedule 4/2, followed (due to PD or toxicity) by sorafenib 400 mg BID
Arm 2
sorafenib 400 mg BID, followed (due to PD or toxicity) by sunitinib 50 mg daily on schedule 4/2 / 1°: PFS
2°: TTP, OS, DCR, cardiotoxicity / 540
NCT00111020:
Treatment protocol for the use of sorafenib in patients with advanced renal cell carcinoma / CP / - / non-randomized, open label, uncontrolled
sorafenib 400 mg PO BID / 1°: safety
2°: radiological evaluations / 2622
NCT00492258:
Sorafenib in treating patients at risk of relapse after undergoing surgery to remove kidney cancer / AC / - / randomized open label
Arm 1
sorafenib 400 mg PO BID
Arm 2
placebo / 1°: DFS
2°: metastasis-free survival, disease-specific survival time, OS, cost effectiveness / 1656
NCT00326898:
Sunitinib or sorafinib in treating patients with kidney cancer that was removed by surgery
[ASSURE] / AC / sunitinib / randomized double blind
Arm A
sorafenib PO BID x 6 weeks + sunitinib PO daily on schedule 4/2
Arm B
sorafenib PO BID x 6 weeks + placebo on schedule 4/2
Arm C
placebo x 6 weeks / 1°: DFS
2°: OS, toxicity, correlatives / 1332
NCT00625378:
Sorafenib long term extension program (STEP) / various / AC / - / non-randomized open label, uncontrolled
sorafenib 400-600 mg PO BID (based on prior trial's dosage) / 1°: long-term safety
2°: NA / 2000
sunitinib / NCT00373113:
A clinical trial comparing efficacy and safety of sunitinib and capecitabine / breast cancer / AC / (capecitabine) / randomized open label
Arm A
capecitabine 1250 mg/m2 BID x 2 weeks q 3 weeks
Arm B
sunitinib 37.5 mg PO daily, continuous / 1°: PFS
2°: TTR, OS, PRO, safety, TTP, OR, DR / 700
sunitinib / NCT00435409:
A study of sunitinib in combination with capecitabine compared with capecitabine in patients with breast cancer / breast cancer / AC / capecitabine / randomized open label with crossover
Arm A
sunitinib 37.5 mg PO daily continuous + capecitabine 1000 mg/m2 PO BID d 1-4 q 3 weeks
Arm B
capecitabine 1500 mg/m2 BID
d 1-4 q 3 weeks
NOTE: at progression, patients may be crossed over to sunitinib alone / 1°: PFS
2°: PRO, 2- and 3-yr survival, overall RR, DR / 430
NCT00393939:
Study of sunitinib in combination with docetaxel vs docetaxel in patients with advanced breast cancer (SUN 1064) / AC / docetaxel / randomized open label
Arm A
sunitinib 37.5 mg PO daily on schedule 2/1 + docetaxel 75 mg/m2 q 3 weeks OR sunitinib 37.5 mg PO daily continuous (in absence of docetaxel)
Arm B
docetaxel 100 mg/m2 q 3 weeks / 1°: PFS
2°: safety, PRO, ORR, DR / 550
NCT00373256:
A study of SU011248 plus paclitaxel versus bevacizumab plus paclitaxel in patients with advanced breast cancer / AC / paclitaxel
(bevacizumab) / randomized open label
Arm A
sunitinib 25 mg PO daily (titration to 37.5 mg) + paclitaxel 90 mg/m2 IV, 3 weekly doses q 28 days
Arm B
bevacizumab 10 mg/kg IV q 2 weeks + paclitaxel as in Arm A / 1°: PFS
2°: safety, PRO, tumor control, OS / 740
NCT00457691:
Study of FOLFIRI chemotherapy with or without sunitinib in patients with metastatic colorectal cancer / CRC / CB / 5-fluorouracil, leucovorin, irinotecan / randomized double blind
Arm A
fluorouracil 400 mg/m2 IV d 1 followed by 2400 mg/m2 IV continuous x 46 hours q 14 d/
leucovorin 200 mg/m2 d 1 q 14 d/
irinotecan 180 mg/m2 IV d 1 q 14 d (FOLFIRI) + sunitinib 37.5 mg PO daily x 28 d
Arm B
FOLFIRI as above + placebo / 1°: PFS
2°: OS, ORR, DR, AEs / 720
sunitinib / NCT00075218:
A study to assess the safety and efficacy of SU11248 in patients with gastrointestinal stromal tumors (GIST) / GIST / CB / - / randomized double blind
Arm A
sunitinib 50 mg PO daily on schedule 4/2
Arm B
placebo / 1°: TTP
2°: OS, PFS, ORR, TTR, DR, correlatives / 357
NCT00085618:
SU011248 in treating patients with malignant gastrointestinal stromal tumor / CB / - / randomized double blind
Arm I
sunitinib PO daily on schedule 4/2
Arm II
placebo / 1°: TTP
2°: safety, tolerability, correlatives, QOL / 357
NCT00094029:
A treatment protocol for patients with gastrointestinal stromal tumor (GIST) who may derive benefit from treatment with SU011248 / AC / - / non-randomized open label
sunitinib 25, 37.5, or 50 mg PO daily / 1°: safety
2°: TTP, overall RR, OS / 1400
NCT00372567:
Safety and effectiveness of daily dosing with sunitinib or imatinib in patients with gastrointestinal stromal tumors / AC / (imatinib) / randomized open label
Arm A
sunitinib 37.5 mg PO daily
Arm B
imatinib 800 mg PO daily / 1°: PFS
2°: safety, tolerability, OS, PRO, OR, pain relief/progression, TTR, DR, TTF / 200
NCT00699374:
Study of sunitinib malate versus sorafenib in patients with inoperable liver cancer / HCC / AC / (sorfenib) / randomized open label
Arm A
sunitinib 37.5 mg PO daily
Arm B
sorafenib 400 mg PO BID / 1°: OS
2°: PFS, TTP, safety, QOL / 1200
NCT00693992:
Sunitinib as maintenance therapy in treating patients with stage III or stage IV non-small cell lung cancer previously treated with combination chemotherapy / NSCLC / AC / - / randomized double blind
Arm I
sunitinib 37.5 mg PO daily qx 21 days
Arm II
placebo / 1°: PFS
2°: toxicity, RR, OS / 156
NCT00457392:
A study in patients with non-small cell lung cancer to test if erlotinib plus SU011248 is better than erlotinib alone / AC / erlotinib / randomized double blind
Arm1
sunitinib 37.5 mg PO daily continuous + erlotinib 150 mg daily continuous
Arm 2
erlotinib as in Arm 1 / 1°: OS
2°: safety, tolerability, PRO, PFS, overall RR, DR / 956
sunitinib / NCT00428597;
A study of sunitinib compared to placebo for patients with advanced pancreatic islet cell tumors / pancreatic (islet cell) / AC / - / randomized double blind
Arm A
sunitinib 37.5 mg PO daily continuous
Arm B
placebo / 1°: PFS
2°: TTR, safety, tolerability, PRO, OS, tumor response, DR / 340
NCT00676650:
Sunitinib plus chemotherapy in patients with metastatic hormone-refractory prostate cancer after failure of docetaxel chemotherapy (SUN 1120) / prostate cancer / AC / prednisone / randomized double blind
Arm A
sunitinib 37.5 mg PO daily continuous + prednisone 5 mg PO BID
Arm B
prednisone as in Arm A + placebo / 1°: OS
2°: PFS, ORR, AEs, QOL / 819
NCT00375674:
A clinical trial comparing efficacy and safety of sunitinib verus placebo for the treatment of patients at high risk of recurrent renal cell cancer (S-TRAC) / RCC / AC / - / randomized double blind
Arm A
sunitinib 50 mg PO daily on schedule 4/2
Arm B
placebo / 1°: DFS
2°: OS, safety, tolerability, PRO / 290
NCT00326898:
Sunitinib or sorafenib in treating patients with kidney cancer that was removed by surgery / RCC / See trial information under "sorafenib" above
NCT00083889:
SU011248 versus interferon-alfa as first-line systemic therapy for patients with metastatic renal cell carcinoma / CB / (interferon-alfa) / randomized
Arm 1
sunitinib 50 mg PO daily on schedule 4/2
Arm 2
interferon-alfa 3 MIU first week, 6 MIU second week, 9MIU thereafter 3 times/week / 1°: PFS
2°: ORR, OS, DR, PRO, safety / 750
NCT00732914:
Sequential study to treat renal cell carcinoma / See trial information under "sorafenib" above
sunitinib / NCT00130897:
Treatment use study with sunitinib (SU011248) for patients with cytokine-refractory metastatic renal cell carcinoma / RCC / AC / - / non-randomized open label
sunitinib 25, 37.5, or 50 mg PO daily / 1°: overall RR
2°: TTP, overall RR, OS / 5000
NCT00720941:
Pazopanib versus sunitinib in the treatment of locally advanced and/or metastatic renal cell carcinoma / See trial information under “pazopanib” above
NCT00428220:
A continuation study using sunitinib malate for patients leaving treatment on a previous sunitinib study / various
(RCC, breast cancer, islet cell carcinoma, GIST) / AC / - / non-randomized open label
sunitinib 37.5 mg PO daily continuous (dose dependent on dose patient received in prior trial) / 1°: safety, tolerability, duration of clinical benefit
2°: NA / 300
vandetanib / NCT00364351:
Efficacy trial comparing ZD6474 with erlotinib in NSCLC after failure of at least one prior chemotherapy / NSCLC / CL / erlotinib / randomized double blind
Arm 1
erlotinib
Arm 2
vandetanib / 1°: PFS comparison
2°: OS comparison / 1243
vandetanib / NCT00418886:
Efficacy study comparing ZD6474 in combination with pemetrexed and pemetrexed alone in 2nd line NSCLC patients (ZEAL) / NSCLC / CL / pemetrexed / randomized double blind
Arm 1
pemetrexed IV
Arm 2
vandetanib PO daily + pemetrexed IV / 1°: PFS comparison
2°: OS comparison / 510
NCT00312377:
ZACTIMA (an anti-EGFR/anti-VEGFR agent) combined with docetaxel compared to docetaxel in non-small cell lung cancer (ZODIAC) / CP / docetaxel / randomized double blind
Arm 1
docetaxel PO
Arm 2
vandetanib PO + docetaxel PO / 1°: improvement in PFS for combination
2°: improvement in OS for combination / 1240
NCT00404924:
ZD6474 (ZACTIMA™) phase III study in EGFR failures / CL / - / randomized double blind
Arm 1
best supportive care
Arm 2
vandetanib PO daily + best supportive care / 1°: improvement in OS
2°: improvements in PFS,DR, safety, tolerability, symptoms of disease / 930
vatalanib / NCT00056459:
Study of oxaliplatin/5-FU/leucovirn plus vatalanib versus oxaliplatin/5-FU/leucovorin in patients iwth metastatic colrectal cancer / CRC / CP / oxaliplatin
fluorouracil
leucovorin / randomized double blind
Arm 1
vatalanib + oxaliplatin/leucovorin/fluorouracil
Arm 2
oxaliplatin/leucovorin/ fluorouracil / 1°: PFS
2°: TTP, TTF, overall RR, safety, tolerability / 1168
NCT00056446:
Study of oxaliplatin/5-FU/leucovorin plus vatalanib versus oxaliplatin/5-FU/leucovorin in patients with previously treated metastatic colorectal cancer / CP / oxaliplatin
fluorouracil
leucovorin / randomized double blind
Arm 1
vatalanib + oxaliplatin/leucovorin/fluorouracil
Arm 2
oxaliplatin/leucovorin/ fluorouracil / 1°: OS
2°: PFS, TTP, TTF, RR, safety, tolerability / 855
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