Drug Class: Angiogenesis and Growth Factor/ Receptor Inhibitors

Angiogenesis Inhibitors: VEGF

First-line treatment with/without extended (maintenance) treatment

Progression Free Survival (months)

Median length of time before the cancer comes back or gets worse

Overall Survival (months)

The length of time where half the patients in the study are still alive

No Prior Therapies

Platinum-Sensitive (Pt-S): Treatment given for recurrence occurring 6 months or more after last platinum-based treatment

Objective Response Rate (%)

Percentage of patients whose tumors shrink or go away after treatment

Progression Free Survival (months)

Median length of time before the cancer comes back or gets worse

1 Prior Therapy 2 Prior Therapies Prior Therapies Not Reported

Platinum-Resistant/Refractory (Pt-R/Rf): Treatment given for recurrence occurring less than 6 months after last platinum-based treatment or for progression during last platinum-based treatment

Objective Response Rate (%)

Percentage of patients whose tumors shrink or go away after treatment

Progression Free Survival (months)

Median length of time before the cancer comes back or gets worse

1 Prior Therapy 2 Prior Therapies 3 Prior Therapies 4 Prior Therapies 5 Prior Therapies 6 Prior Therapies Prior Therapies Not Reported

Treatment given for recurrence occurring at any time after last platinum-based treatment

Objective Response Rate (%)

Percentage of patients whose tumors shrink or go away after treatment

Progression Free Survival (months)

Median length of time before the cancer comes back or gets worse

2 Prior Therapies

Angiogenesis Inhibitors: VEGF/DLL4

Platinum-Resistant/Refractory (Pt-R/Rf): Treatment given for recurrence occurring less than 6 months after last platinum-based treatment or for progression during last platinum-based treatment

Objective Response Rate (%)

Percentage of patients whose tumors shrink or go away after treatment

Progression Free Survival (months)

Median length of time before the cancer comes back or gets worse

4 Prior Therapies

Treatment given for recurrence occurring at any time after last platinum-based treatment

Objective Response Rate (%)

Percentage of patients whose tumors shrink or go away after treatment

Progression Free Survival (months)

Median length of time before the cancer comes back or gets worse

4 Prior Therapies

Angiogenesis Inhibitors: VEGF

First-line treatment with/without extended (maintenance) treatment

For more detailed information, please click on the clinical trial ID number.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Standard of Care Targeted Drugs
NCT00262847; GOG-218 III Bevacizumab, Carboplatin, Paclitaxel Prescribing Information A Phase III Trial of Carboplatin and Paclitaxel Plus Placebo Versus Carboplatin and Paclitaxel Plus Concurrent Bevacizumab (NSC # 704865) Followed by Placebo, Versus Carboplatin and Paclitaxel Plus Concurrent and Extended Bevacizumab, in Women With Newly Diagnosed, Previously Untreated, Stage III or IV Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer (GOG218)

Improved PFS, but no OS difference with addition of bevacizumab to carboplatin+paclitaxel; potential benefit for patients with stage IV disease

CarboPt+Pac+Bev w/ Bev maint vs CarboPt+Pac+Bev vs CarboPt+Pac:

All:
PFS: 14.1 vs 11.2 vs 10.3 months*
OS: 43.4 vs 40.8 vs 41.1 months

Stage IV patients:
OS: 42.8 vs 34.5 vs 32.6 months

pub 2019

NCT00483782; ICON7 III Bevacizumab, Carboplatin, Paclitaxel ICON7 - A Randomised, Two-Arm, Multi-Centre Gynaecologic Cancer InterGroup Trial of Adding Bevacizumab to Standard Chemotherapy (Carboplatin and Paclitaxel) in Patients With Epithelial Ovarian Cancer

Improved PFS and OS with addition of bevacizumab to carboplatin+paclitaxel in high risk patients

CarboPt+Pac+Bev w/ Bev maint vs CarboPt+Pac:

All:
PFS: 19.9 vs 17.5 months
OS: 45.5 vs 44.6 months (restricted mean survival)
High risk:
PFS: 16.0 vs 10.5 months*
OS: 39.3 vs 34.5 months* (restricted mean survival)

pub 2011; 2015

Drugs in Clinical Development
NCT00951496; GOG-252 III Bevacizumab, Carboplatin, Cisplatin, Paclitaxel A Phase III Clinical Trial of Bevacizumab With IV Versus IP Chemotherapy in Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma

Compared to the IV reference arm, PFS was not significantly increased with either IP regimen

IV CarboPt+Pac+Bev w/ Bev maint vs IP CarboPt+Pac+Bev w/ Bev maint vs IP CisPt+Pac+Bev w/ Bev maint:

PFS: 24.9 vs 27.4 vs 26.2 months
OS: 75.5 vs 78.9 vs 72.9 months

pub 2019

*Statistically significant result

Platinum-Sensitive (Pt-S): Treatment given for recurrence occurring 6 months or more after last platinum-based treatment

For more detailed information, please click on the clinical trial ID number.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Standard of Care Targeted Drugs
NCT00434642; OCEANS III Bevacizumab, Carboplatin, Gemcitabine Prescribing Information A Phase III, Multicenter, Randomized, Blinded, Placebo-controlled Trial of Carboplatin and Gemcitabine Plus Bevacizumab in Patients With Platinum-sensitive Recurrent Ovary, Primary Peritoneal, or Fallopian Tube Carcinoma (OCEANS)

Improved ORR and PFS with addition of bevacizumab to carboplatin and gemcitabine, but no OS difference

CarboPt+Gem+Bev vs CarboPt+Gem+Placebo:

ORR: 78.5 vs 57.4%*
PFS: 12.4 vs 8.4 months*
OS: 33.6 vs 32.9 months

pub 2012; 2015

NCT00565851; GOG-213 III Bevacizumab, Carboplatin, Paclitaxel Prescribing Information A Phase III Randomized Controlled Clinical Trial of Carboplatin and Paclitaxel (or Gemcitabine) Alone or in Combination With Bevacizumab (NSC #704865) Followed by Bevacizumab and Secondary Cytoreductive Surgery in Platinum-Sensitive, Recurrent Ovarian, Peritoneal Primary and Fallopian Tube Cancer. NCI-Supplied Agents: Bevacizumab (NSC #704865) (GOG 0213)

Improved ORR, PFS and OS with the addition of bevacizumab to carboplatin+paclitaxel

CarboPt+Pac+Bev vs CarboPt+Pac:

ORR: 78 vs 59%*
PFS: 13.8 vs 10.4 months*
OS: 42.2 vs 37.3 months*

pub 2017

NCT01837251 III Bevacizumab, Carboplatin, Gemcitabine, Liposomal doxorubicin A Prospective Randomized Phase III Trial of Carboplatin/Gemcitabine/Bevacizumab vs. Carboplatin/Pegylated Liposomal Doxorubicin/Bevacizumab in Patients With Platinum-sensitive Recurrent Ovarian Cancer

Improved PFS and OS with addition of liposomal doxorubicin to carboplatin+bevacizumab compared to gemcitabine

CarboPt+Gem+Bev vs CarboPt+PLD+Bev:

PFS: 11.7 vs 13.3 months*
OS: 27.8 vs 31.9 months*

pub 2020

NCT01802749; MITO16B-MaNGO OV2B III Bevacizumab, Carboplatin, Gemcitabine, Liposomal doxorubicin, Paclitaxel Multicenter Phase III Randomized Study With Second Line Chemotherapy Plus or Minus Bevacizumab in Patients With Platinum Sensitive Epithelial Ovarian Cancer Recurrence After a Bevacizumab/Chemotherapy First Line

Rechallenge with bevacizumab in combination with platinum-based doublets is associated with a significantly prolonged PFS

CarboPt+Pac+Bev vs CarboPt+Pac:

ORR: 74.6 vs 65.7%
PFS: 11.8 vs 8.8 months*

pub 2021

Drugs in NCCN Guidelines
NCT01305213 II Bevacizumab, Fosbretabulin A Randomized Phase II Evaluation of Single-Agent Bevacizumab (NSC #704865) and Combination Bevacizumab With Fosbretabulin Tromethamine (CA4P) (NSC #752293) in the Treatment of Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma

Improved PFS with addition of fosbretabulin to bevacizumab

Bev+Fos vs Bev:

PFS: 7.6 vs 6.1 months

pub 2020

NCT02354131; AVANOVA II Bevacizumab, Niraparib Part 1: AVANOVA1 - A Phase I Study to Evaluate the Safety and Tolerability of Bevacizumab-niraparib Combination Therapy and Determine the Recommended Phase 2 Dose (RP2D) in Women With Platinum-sensitive Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer Part 2: AVANOVA2 - A Two-arm, Open-label, Phase II Randomized Study to Evaluate the Efficacy of Niraparib Versus Niraparib-bevacizumab Combination in Women With Platinum-sensitive Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer.

Promising improvement of activity with niraparib+bevacizumab compared to niraparib alone

Nir+Bev vs Nir:

ORR: 62 vs 30%*
PFS: 12.5 vs 5.5 months*

pub 2019, abs May 2020 and poster

Drugs in Clinical Development
NCT01010126 II Bevacizumab, Temsirolimus A Phase 2 Trial of Temsirolimus and Bevacizumab in Patients With Endometrial, Ovarian, Hepatocellular Carcinoma, Carcinoid or Islet Cell Cancer

Bevacizumab+temsirolimus has activity in Pt-S ovarian cancer but with substantial toxicity

ORR: 24%

abs Jun 2013 and poster

NCT01031381 II Bevacizumab, Everolimus Phase II Study of RAD001 and Bevacizumab in Recurrent Ovarian, Peritoneal, and Fallopian Tube Cancer An Investigator-initiated, Single-institution Trial at Magee-Womens Hospital

Bevacizumab+everolimus does not improve responses compared to bevacizumab alone in Pt-S ovarian cancer patients, but selected patients with alterations in the PI3K/mTOR pathway may have benefit

ORR: 16.7%

pub 2020

NCT02873962 II Bevacizumab, Nivolumab A Phase II Study With a Safety lead-in of Nivolumab in Combination With Bevacizumab or in Combination With Bevacizumab and Rucaparib for the Treatment of Relapsed Epithelial Ovarian, Fallopian Tube or Peritoneal Cancer

Encouraging activity of bevacizumab+nivolumab combination in platinum sensitive patients

ORR: 40%
CBR: 70%
PFS: 12.1 months

pub 2019

NCT02606305; FORWARD II Ib/II Bevacizumab, Carboplatin, Mirvetuximab soravtansine A Phase 1b/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Mirvetuximab Soravtansine (IMGN853) in Combination With Bevacizumab, Carboplatin, Pegylated Liposomal Doxorubicin, Pembrolizumab, or Bevacizumab+Carboplatin in Adults With Folate Receptor Alpha Positive Advanced Epithelial Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer

Encouraging activity of mirvetuximab soravtansine combinations in FRalpha+ patients

Mir+CarboPt:

ORR: 71%
PFS: 15 months

Mir+CarboPt+Bev:

1-2 prior therapies:
ORR: 81%
PFS: 12.0 months

1 prior therapy:
ORR: 90%
PFS: 11.9 months

pub 2018, abs Oct 2020

NCT02606305; FORWARD II-2 Ib/II Bevacizumab, Mirvetuximab soravtansine A Phase 1b/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Mirvetuximab Soravtansine (IMGN853) in Combination With Bevacizumab, Carboplatin, Pegylated Liposomal Doxorubicin, Pembrolizumab, or Bevacizumab+Carboplatin in Adults With Folate Receptor Alpha Positive Advanced Epithelial Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer

The combination of mirvetuximab soravtansine with bevacizumab demonstrates an encouraging ORR in platinum sensitive patients with high FRalpha expression

ORR: 69%

abs May 2020 and presentation

NCT02734004; MEDIOLA I/II Bevacizumab, Durvalumab, Olaparib A Phase I/II Study of MEDI4736 (Anti-PD-L1 Antibody) in Combination With Olaparib (PARP Inhibitor) in Patients With Advanced Solid Tumors

Promising activity of bevacizumab+olaparib+durvalumab in non-gBRCA MUT patients regardless of LOH score and mutation status of common DDR genes

ORR: 87%
CBR: 77%
PFS: 14.7 months

abs Sep 2020

*Statistically significant result

Platinum-Resistant/Refractory (Pt-R/Rf): Treatment given for recurrence occurring less than 6 months after last platinum-based treatment or for progression during last platinum-based treatment

For more detailed information, please click on the clinical trial ID number.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Standard of Care Targeted Drugs
NCT00976911; AURELIA III Bevacizumab, Liposomal doxorubicin, Paclitaxel, Topotecan Prescribing Information AURELIA: A Multi-center, Open-label, Randomised, Two-arm Phase III Trial of the Effect on Progression Free Survival of Bevacizumab Plus Chemotherapy Versus Chemotherapy Alone in Patients With Platinum-resistant, Epithelial Ovarian, Fallopian Tube or Peritoneal Cancer

Improved ORR and PFS with addition of bevacizumab to liposomal doxorubicin, paclitaxel or topotecan (most evident with paclitaxel), but no OS benefit

Pac/PLD/Top+Bev vs Pac/PLD/Top:

ORR: 28.2 vs 12.5%*
PFS: 6.7 vs 3.4 months*

pub 2014; 2015

UMIN000017247; JGOG3023 II Bevacizumab, Gemcitabine, Liposomal doxorubicin, Paclitaxel, Topotecan An open-label, randomized, phase II trial evaluating the efficacy and safety of standard of care with or without Bevacizumab in Platinum-resistant ovarian cancer patients previously treated with Bevacizumab for front-line or Platinum-sensitive ovarian cancer: -JGOG3023 trial-

Retreatment with bevacizumab is effective and AEs are manageable for platinum resistant recurrent ovarian cancer previously treated with bevacizumab for front-line or platinum sensitive recurrence

Gem/Pac/PLD/Top+Bev vs Gem/Pac/PLD/Top:

ORR: 25.0 vs 13.7%
PFS: 4.0 vs 3.1 months*
OS: 15.3 vs 11.3 months

pub 2021

Drugs in NCCN Guidelines
NCT00097019 II Bevacizumab A Multicenter, Single-Arm, Phase II Trial of Bevacizumab in Subjects With Platinum-Resistant Epithelial Carcinoma of the Ovary or Primary Peritoneal Carcinoma for Whom Subsequent Doxil or Topotecan Therapy Has Failed

Bevacizumab has single-agent activity, but risk of GI-related adverse events

ORR: 15.9%
PFS: 4.4 months
OS: 10.7 months

pub 2007

Retrospective Study: Bevacizumab and Cyclophosphamide II Bevacizumab, Cyclophosphamide The combination of intravenous bevacizumab and metronomic oral cyclophosphamide is an effective regimen for platinum-resistant recurrent ovarian cancer

Cyclophosphamide+bevacizumab is an effective, well-tolerated combination in heavily pretreated patients

ORR: 42.4%
PFS: 3 months

pub 2013

Drugs in Clinical Development
NCT01010126 II Bevacizumab, Temsirolimus A Phase 2 Trial of Temsirolimus and Bevacizumab in Patients With Endometrial, Ovarian, Hepatocellular Carcinoma, Carcinoid or Islet Cell Cancer

Bevacizumab+temsirolimus has activity in platinum resistant ovarian cancer but with substantial toxicity

ORR: 32.1%

abs Jun 2013 and poster

NCT01031381 II Bevacizumab, Everolimus Phase II Study of RAD001 and Bevacizumab in Recurrent Ovarian, Peritoneal, and Fallopian Tube Cancer An Investigator-initiated, Single-institution Trial at Magee-Womens Hospital

Bevacizumab+everolimus does not improve responses compared to bevacizumab alone in Pt-R ovarian cancer patients, but selected patients with alterations in the PI3K/mTOR pathway may have benefit

ORR: 11.1%
2 clear cell w/ PI3K pathway and ARID1A alterations (1PR, 1SD > 9 months)

pub 2020

NCT01091259 II Bevacizumab, Irinotecan Phase II Study of Irinotecan in Combination With Bevacizumab for the Treatment of Recurrent Ovarian Cancer

Bevacizumab+irinotecan shows encouraging activity in heavily pre-treated platinum resistant patients, including those treated with topotecan and/or avastin

ORR: 21%
DCR: 63.2%

pub 2017

NCT02659384; EORTC-1508 II Acetylsalicylic acid, Atezolizumab, Bevacizumab A Phase II Study of the Anti-PDL1 Antibody Atezolizumab, Bevacizumab and Acetylsalicylic Acid to Investigate Safety and Efficacy of This Combination in Recurrent Platinum-resistant Ovarian, Fallopian Tube or Primary Peritoneal Adenocarcinoma

The addition of atezolizumab to bevacizumab (with or without acetylsalicylic acid) improves PFS and TFST

Bev vs Bev+Ate vs Bev+Ate+Asa:

ORR: 24.1 vs 20.7 vs 27.6%
PFS: 2.3 vs 4.1 vs 4.0 months
TFST: 3.0 vs 5.3* vs 5.8 months*

abs Sep 2021

NCT02853318 II Bevacizumab, Cyclophosphamide, Pembrolizumab A Phase II Evaluation of Pembrolizumab in Combination With IV Bevacizumab and Oral Metronomic Cyclophosphamide in the Treatment of Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Bevacizumab+pembrolizumab+cyclophosphamide is well tolerated and demonstrates clinical benefit and durable treatment responses

ORR: 43.3%
DCR: 95%
PFS: 7.6 months

pub 2020

NCT02873962 II Bevacizumab, Nivolumab A Phase II Study With a Safety lead-in of Nivolumab in Combination With Bevacizumab or in Combination With Bevacizumab and Rucaparib for the Treatment of Relapsed Epithelial Ovarian, Fallopian Tube or Peritoneal Cancer

Bevacizumab+nivolumab shows activity in Pt-R patients, independent of PD-L1 expression

ORR: 16.7%
CBR: 33.3%
PFS: 7.7 months

pub 2019

NCT03093155 II Bevacizumab, Ixabepilone A Randomized Phase II Evaluation of Weekly Ixabepilone With or Without Biweekly Bevacizumab in Recurrent or Persistent Platinum-resistant/Refractory Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancers

Bevacizumab+ixabepilone is a well-tolerated, effective combination for treatment of platinum/taxane resistant ovarian cancer that extends both PFS/OS relative to ixabepilone monotherapy and prior receipt of bevacizumab should not preclude use of ixabepilone+bevacizumab

Bev+Ixa vs Ixa:
ORR: 33 vs 8%*
PFS: 5.5 vs 2.2 months*
OS: 10.0 vs 6.0 months*

abs Mar 2021

NCT03574779; OPAL II Bevacizumab, Niraparib, Dostarlimab Phase 2 Multicohort Study to Evaluate the Safety and Efficacy of Novel Treatment Combinations in Patients With Recurrent Ovarian Cancer

Triplet therapy with bevacizumab, niraparib and dostarlimab is tolerable and demonstrates clinical activity in patients with BRCA WT platinum resistant ovarian cancer without HRR gene mutations

ORR: 17.9%
DCR: 76.9%
PFS: 7.6 months

w/ prior Bev: ORR: 6%
w/o prior Bev: ORR: 27%

abs Mar 2021

NCT02606305; FORWARD II Ib/II Bevacizumab, Mirvetuximab soravtansine A Phase 1b/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Mirvetuximab Soravtansine (IMGN853) in Combination With Bevacizumab, Carboplatin, Pegylated Liposomal Doxorubicin, Pembrolizumab, or Bevacizumab+Carboplatin in Adults With Folate Receptor Alpha Positive Advanced Epithelial Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer

Encouraging activity of bevacizumab+mirvetuximab soravtansine in FRalpha+ patients

ORR: 39%
PFS: 6.9 months

pub 2020

NCT02606305; FORWARD II-2 Ib/II Bevacizumab, Mirvetuximab soravtansine A Phase 1b/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Mirvetuximab Soravtansine (IMGN853) in Combination With Bevacizumab, Carboplatin, Pegylated Liposomal Doxorubicin, Pembrolizumab, or Bevacizumab+Carboplatin in Adults With Folate Receptor Alpha Positive Advanced Epithelial Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer

The combination of mirvetuximab soravtansine with bevacizumab demonstrates an encouraging ORR in platinum resistant patients with high FRalpha expression

ORR: 59%

abs May 2020 and presentation

NCT01633970 Ib Atezolizumab, Bevacizumab A Phase Ib Study of the Safety and Pharmacology of Atezolizumab (Anti-PD-L1 Antibody) Administered With Bevacizumab and/or Chemotherapy in Patients With Advanced Solid Tumors

Bevacizumab+atezolizumab induces durable responses and/or disease stabilization in some patients with platinum-resistant ovarian cancer; the safety profiles are consistent with those of each agent

ORR: 15%
PFS: 4.9 months
OS: 10.2 months

pub 2020

NCT03596281; PEMBOV I Bevacizumab, Liposomal doxorubicin, Pembrolizumab An Open-label Phase 1 of Pembrolizumab in Combination With Bevacizumab and Pegylated Liposomal Doxorubicin in Patients With Platinum Resistant Epithelial Ovarian Cancer

Bevacizumab+liposomal doxorubicin+pembrolizumab is well tolerated and demonstrate durable responses in platinum resistant ovarian cancer patients

Bev+Pem:
ORR: 26.3%
DCR: 78.9%

Bev+PLD+Pem:
ORR: 32%
DCR: 74%
CBR: 53%

abs Jun 2021 and poster, abs Nov 2021

*Statistically significant result

Treatment given for recurrence occurring at any time after last platinum-based treatment

For more detailed information, please click on the clinical trial ID number.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Drugs in Clinical Development
NCT00072566 II Bevacizumab, Cyclophosphamide Phase II Clinical Trial of Bevacizumab (NSC 704865) and Low Dose Oral Cyclophosphamide in Recurrent Ovarian Cancer, Primary Peritoneal Carcinoma

Promising response rates of bevacizumab+cyclophosphamide combination

ORR: 24%
PFS: 7.2 months

pub 2008

Angiogenesis Inhibitors: VEGF/DLL4

Platinum-Resistant/Refractory (Pt-R/Rf): Treatment given for recurrence occurring less than 6 months after last platinum-based treatment or for progression during last platinum-based treatment

For more detailed information, please click on the clinical trial ID number.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Drugs in Clinical Development
NCT03030287 Ib Navicixizumab, Paclitaxel A Phase 1b Study of OMP-305B83 Plus Weekly Paclitaxel in Subjects With Platinum Resistant Ovarian, Primary Peritoneal or Fallopian Tube Cancer

Promising activity of navicixizumab+paclitaxel in heavily pretreated patients

ORR: 43.2%
PFS: 7.3 months

abs Mar 2020, poster Oct 2021

Treatment given for recurrence occurring at any time after last platinum-based treatment

For more detailed information, please click on the clinical trial ID number.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Drugs in Clinical Development
NCT01946074 I Dilpacimab A Multicenter, Phase 1/1b, Open-Label, Dose-Escalation Study of ABT-165, a Dual Variable Domain Immunoglobulin in Subjects With Advanced Solid Tumors

Dilpacimab (ABT-165) monotherapy is well tolerated and demonstrates anti-tumor activity with anti-VEGF-like toxicities in refractory ovarian cancer

ORR: 25%

pub 2021

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