Review Article

New Hypothesis on Pathogenesis of Ovarian Cancer Lead to Future Tailored Approaches

Table 2

Ongoing clinical trials on target therapies in epithelial ovarian cancer.

AgentStudyPhaseProtocol IDS

PARP inhibitors
 OlaparibCediranib and Olaparib in Combination for Recurrent Ovarian or Triple-Negative Breast CancerI/IIDFCI 09-293
 EE7449An open-label, multicenter, phase 1/2 study of poly(ADP-Ribose) polymerase (PARP) inhibitor E7449 as single agent in subjects with advanced solid tumors or With B-cell malignancies and in combination with temozolomide (TMZ) or with carboplatin and paclitaxel in subjects With advanced solid tumorsI/IIE7449-E044-101
 OlaparibPhase Ib study of olaparib plus weekly carboplatin and paclitaxel in relapsed ovarian cancerI/IIISS22810034
 VeliparibVeliparib and topotecan for relapsed ovarian cancer with negative or unknown BRCA statusI/IIVeTo
 RucaparibRucaparib(CO-338; formally called AG-014699 or PF-0136738) in treating patients with locally advanced or metastatic breast cancer or advanced ovarian cancerIICDR0000593558
 VeliparibVeliparib and topotecan hydrochloride in treating patients with solid tumors, relapsed or refractory ovarian cancer, or primary peritoneal cancerI/IINCI-2011-00312
 VeliparibVeliparib monotherapy for relapsed ovarian cancer with BRCA mutationI/IIVeli-BRCA
 VeliparibVeliparib and floxuridine in treating patients with metastatic epithelial ovarian, primary peritoneal cavity, or fallopian tube cancerINCI-2012-02767
BKM120/olaparibPhase I of BKM120/olaparib for triple negative breast cancer or high-grade serous ovarian cancerI12-159
 ABT-888ABT-888 in treating patients with malignant solid tumors that did not respond to previous therapyINCI-2011-01472
 ABT-888Carboplatin, paclitaxel, bevacizumab, and ABT-888 in treating patients with newly diagnosed stage II, stage III, or stage IV ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancerINCI-2011-03730
 ABT-767Study of ABT-767 in subjects with breast cancer 1 and breast cancer 2 (BRCA 1 and BRCA 2) mutations and solid tumors or high-grade serous ovarian, fallopian tube, or primary peritoneal cancerIM10-976
 VeliparibVeliparib, paclitaxel, and carboplatin in treating patients with solid tumors that are metastatic or cannot be removed by surgery and liver or kidney dysfunctionINCI-2011-02500
 VeliparibVeliparib and liposomal doxorubicin hydrochloride in treating patients with recurrent ovarian cancer, fallopian tube cancer, primary peritoneal cancer, or metastatic breast cancerICDR0000674917
 VeliparibPhase II study of veliparib in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who carry a germline BRCA 1 or BRCA 2 mutationIIGOG-0280
 VeliparibVeliparib, oxaliplatin, and capecitabine in treating patients with advanced solid tumorsINCI-2011-02543
 OlaparibOlaparib in combination with carboplatin for refractory or recurrent women's cancersI110022
 VeliparibVeliparib, doxorubicin hydrochloride, and carboplatin in treating patients with recurrent ovarian cancer, primary peritoneal cancer, or fallopian tube cancerINCI-2011-01977
 AZD2281AZD2281 plus carboplatin to treat breast and ovarian cancersI080092

VEGF inhibitors
 RAD001 + BevacizumabStudy of RAD001 and bevacizumab in recurrent ovarian, peritoneal, and fallopian tube cancersII09-01-RAD001BEV
 VB-111 (ANTI VEGF)A phase I/II trial of VB-111 and paclitaxel for recurrent platinum-resistant müllerian cancerI/IIVB-111-157
 DalanterceptPhase II trial of dalantercept to treat ovarian, fallopian tube, or primary peritoneal cancerIIGOG-0170R
 Endostar Endostar and/or cisplatin for treatment of malignant pleural effusion or ascitesIISIM-90
 PazopanibA randomized study of safety and efficacy of pazopanib and gemcitabine in persistent or relapsed ovarian cancerII16153
 PazopanibPhase I clinical and pharmacokinetic study of pazopanib in a population of frail elderly patients according SIOG criteriaI11GENE06
 PazopanibWeekly paclitaxel with or without pazopanib in platinum-resistant or refractory ovarian cancerIIMITO-11
 PazopanibA phase I/II study of pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant recurrent, pretreated ovarian cancerI/II3107000
 PazopanibPazopanib hydrochloride, paclitaxel, and carboplatin in treating patients with refractory or resistant ovarian epithelial cancer, fallopian tube cancer, or peritoneal cancerI/IICDR0000703686
 PazopanibPazopanib and weekly topotecan in patients with recurrent ovarian cancer (TOPAZ)I/IIPazTo_2010
 PazopanibPaclitaxel with or without pazopanib hydrochloride in treating patients with persistent or recurrent ovarian epithelial, fallopian tube, or peritoneal cavity cancerIINCI-2011-03635
 BIBF1120 Doxorubicin + BIBF 1120 in patients with ovarian cancerI/IIGYN10-149
 BIBF1120Daily low dose chemotherapy and BIBF 1120 in advanced ovarian cancerIIUCL/10/0470
 BIBF 1120BIBF 1120 in bevacizumab-resistant, persistent, or recurrent epithelial ovarian cancerIIPro00033060
 BIBF1120BIBF 1120 + carboplatin/pegylated liposomal doxorubicin (PLD) in patients with ovarian cancer (OC)I1199.119

mTOR inhibitors
 TemsirolimusA study of combination of temsirolimus (Torisel) and pegylated liposomal doxorubicin (PLD, Doxil/Caelyx) in advanced or recurrent breast, endometrial, and ovarian cancerIUMCNONCO200902
 SirolimusSirolimus and vaccine therapy in treating patients with stage II–IV ovarian epithelial, fallopian tube, or primary peritoneal cavity cancerII 199911
 EverolimusCarboplatin, Pegylated Liposomal Doxorubicin Hydrochloride, and Everolimus in Treating Patients With Relapsed Ovarian Epithelial, Fallopian Tube, or Peritoneal Cavity CancerIIRB 10-019
 TemsirolimusTemsirolimus, carboplatin, and paclitaxel as first-line therapy in treating patients with newly diagnosed stage III or stage iv clear cell ovarian cancerIINCI-2011-02653
 Everolimus + bevacizumabBevacizumab with or without everolimus in treating patients with recurrent or persistent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancerIICDR0000640439
 Temsirolimus + bevacizumabTemsirolimus and bevacizumab in treating patients with advanced endometrial, ovarian, liver, carcinoid, or islet cell cancerIINCI-2012-02086
 TemsirolimusActivity, tolerability, and safety of temsirolimus in women with ovarian cancer who progressed during previous platinum chemotherapy or within 6 months after therapy or advanced endometrial carcinomaIIAGO-GYN 8
 TemsirolimusA Phase II study of sunitinib or temsirolimus in patients with advanced rare tumorsIII206

Anti-HER2/Anti-EGFR
 LapatinibLapatinib and paclitaxel in treating patients with advanced solid tumorsIUCSF CC#05591
 TCMC-TrastuzumabSafety study of 212Pb-TCMC-trastuzumab radio immunotherapyIAREVAMED01
 PertuzumabA study of pertuzumab in combination with standard chemotherapy in women with recurrent platinum-resistant epithelial ovarian cancer and low HER3 mRNA expressionIIMO28113
 MGAH22 Anti HER2Safety study of MGAH22 in HER2-positive carcinomaICP-MGAH22-01
 PanitumumabCarboplatin-based chemotherapy with or without panitumumab in platinum-sensitive recurrent ovarian cancerIIGMIHO-008/2009_AG56
 PanitumumabPanitumumab and gemcitabine in relapsed ovarian cancerIIWIH 20050782
 OSI906 IGFR inhibitorA study evaluating intermittent and continuous OSI-906 and weekly paclitaxel in patients with recurrent epithelial ovarian cancer (and other solid tumors)I/IIOSI-906-202

Kinase inhibitors
 SorafenibEfficacy and safety study of sorafenib with topotecan in patients with platinum-resistant recurrent ovarian cancerIITRIAS 2009
 Sorafenib Sorafenib and bevacizumab to treat ovarian, fallopian, and peritoneal cancersII070058
 SorafenibOral Hydroxychloroquine Plus Oral Sorafenib to Treat Patients With Refractory or Relapsed Solid TumorsICTRC 11-71
 SunitinibSunitinib and hydroxychloroquine in treating patients with advanced solid tumors that have not responded to chemotherapyINCI-2012-03112
 CabozantinibCabozantinib or paclitaxel in treating patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cavity cancerIINCI-2012-02058
 AT13148Phase I study of AT13148, a novel AGC kinase inhibitorICRUKD/12/001
 VS-6063Phase I/Ib study of paclitaxel in combination with VS-6063 in patients with advanced ovarian cancerIVS-6063-101

Miscellanea
 MK-1775 (Wee-1 inhibitor)Study with Wee-1 inhibitor MK-1775 and carboplatin to treat p53 mutated refractory and resistant ovarian cancerIIM10MKO/MK1775-009
 MK-1775 (Wee-1 inhibitor)A study of MK-1775 in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone for participants with platinum-sensitive ovarian tumors with the P53 gene mutation (MK-1775-004 AM4)II1775-004
 BKM 120
 (mutate PTEN; PIK3CA
 inhibitor)
BKM120 in advanced, metastatic, or recurrent endometrial cancersIIHCI47841
 BYL719 (PI3KNASE
 inhibitor)
A phase Ib/II study of the combination of BYL719 plus AMG 479 in adult patients with selected solid tumorsI/IICBYL719X2105J
 Cyclin dependent kinases 4
 and 6
An open label study of the efficacy and safety of PD0332991, a selective inhibitor of the cyclin dependent kinases 4 and 6 in patients with recurrent ovarian cancer demonstrating Rb proficiency and Low p16 expressionII11-003234
 Triciribine (AKT inhibitor)Triciribine and carboplatin in ovarian cancerI/IIMCC-17035
 LY2228820 (MAP KINASI)A study of LY2228820 for recurrent ovarian cancerI/II12517
 Inhibitor AKT
  (GSK2110183)
Dose-finding study on platinum-resistant ovarian cancerI/IIPKB116611
 MEK inhibitorTrial of MEK inhibitor and PI3K/mTOR inhibitor in subjects with locally advanced or metastatic solid tumorsIEMR 200066-006
 MSC2015103B or pimasertib
  (MEK inhibitor)
MSC2015103B in solid tumorsIEMR 200064-001
 MEK162A study of MEK162 and paclitaxel in patients with epithelial ovarian, fallopian tube, or peritoneal cancerIARRAY-162-112
 GSK2636771A Phase I/IIa, first time in human, study of GSK2636771 in subjects with advanced solid tumors with phosphatase and tensin homolog (PTEN) deficiencyI/II115717
 OMP-54F28
  (antagonist of the Wnt
 pathway
A dose escalation study of OMP-54F28 in subjects with solid tumorsI54F28-001