Table 3. Clinical Trials of PARP inhibitors in ovarian cancer.
| Agent | NCT no./trial name | Phase | Population | Study design | Interventions | Primary outcome measure | Selected additional outcome measures | Start date- estimated completion |
|---|---|---|---|---|---|---|---|---|
|
Monotherapy trials | ||||||||
| Niraparib | NCT01847274 NOVA | III | Platinum-sensitive, recurrent gBRCAm OC or HGSOC | Randomised double-blind, placebo-controlled, parallel-group | Oral niraparib, placebo | PFS | PRO, chemotherapy-free interval, OS | Jun 2013-Oct 2016 Jun 2016 (primary data) |
| Niraparib | NCT02354586 QUADRA | II | Advanced, relapsed HGSOC following completion of at least 3 prior chemotherapy regimens | Single-arm, open-label | Oral niraparib | Antitumour activity | PFS, disease control rate, safety | Mar 2015- Jan 2016 Jan 2016 (primary data) |
| Niraparib | NCT02655016 PRIMA | III | HRD-positive tumours OC, as identified with a centralised HRD test, at high risk for PD, as identified by the stage of cancer and previous response to surgery | Randomised, double-blind, placebo-controlled, parallel group | Oral niraparib, placebo | PFS | OS, safety and tolerablilty, PRO, TTP | Apr 2016-Mar 2018 Mar 2018 (primary data) |
| Olaparib | NCT02282020 SOLO3 | III | Platinum-sensitive relapsed, gBRCAm OC | Randomised open-label controlled, parallel group | Oral olaparib (300 mg tablets) vs physicians choice single-agent chemo-therapy | PFS | OS, TTP, PFS, QoL | Feb 2015-Dec 2019 Dec 2017 (primary data) |
| Olaparib | NCT02477644 | III | Advanced FIGO stage IIIB - IV HGSOC or endometrioid ovarian, fallopian tube, or peritoneal cancer treated with standard first-line platinum-taxane chemotherapy plus bevacizumab | Randomised double blind | Oral olaparib 300 mg tablets, placebo | PFS | - | Apr 2015–Apr 2022 Apr 2022 (primary data) |
| Olaparib | NCT02489006 | II | Platinum sensitive recurrent HGSOC, primary peritoneal, and fallopian tube cancer | Randomised, open label | Oral olaparib, platinum-based chemotherapy | Difference in PAR or PARP1 levels before and after treatment, mutations in BRCA1/2, RAD51B, RAD51C, RAD51D, PPM1D, FANCM, BRIP1, PALB2 and BARD1 in germline tissue compared to tumour tissue | Safety, response rate, duration of PFS, | Jun 2015–Jun 2019 Dec 2018 (primary data) |
| Olaparib | NCT00628251 | II | Measurable BRCA1- or BRCA2-positive advanced ovarian cancer which has failed previous platinum therapy. | Randomised open-label, parallel study | Oral olabarib 200 mg BID; or 400 mg BID, liposomal doxorubicin | PFS, ORR, DoR, CA-125 levels | Safety | Jul 2008–Dec 2015 Sep 2009 (primary data) |
| Olaparib | NCT00753545 | II | Platinum sensitive relapsed serous ovarian cancer following treatment with two or more platinum containing regimens | Randomised double blind, parallel group | Oral olabarib 400 mg BID, placebo | PFS | OS, ORR, disease control rate, DoR | Aug 2008–Nov 2012 Jun 2010 (primary data) |
| Olaparib | NCT01844986 SOLO-1 | III | Newly diagnosed, high-risk advanced, gBRCAm OC in complete or partial response following first line platinum therapy | Randomised double-blind, placebo-controlled, parallel-group | Oral olaparib (300 mg tablets), placebo | PFS | OS, TTP, QoL, safety | Aug 2013-Jan 2023 Feb 2017 (primary data) |
| Olaparib | NCT01874353 SOLO2 | III | Platinum-sensitive, relapsed gBRCAm high-grade OC or high grade endometrial cancer with CR or PR following platinum-based chemotherapy | Randomised double-blind, placebo-controlled, parallel-group | Oral olaparib (300 mg tablets), placebo | PFS | OS, TTP, QOL, safety | Sep 2013-Apr 2021 Sep 2016 (primary data) |
| Olaparib | NCT02392676 | III | Platinum sensitive relapsed gBRCAm, ovarian cancer in CR or PR following platinum-based chemotherapy | Randomised double-blind, parallel group | Oral olaparib, placebo | PFS using modified RECIST in cohort of patients with sBRCA ovarian cancer | PFS, OS, TTP | July 2016 -June 2019 June 2019 (primary data) |
| Rucaparib | NCT00664781 | II | Advanced or metastatic gBRCAm breast cancer or advanced ovarian cancer. | Dose-escalation study followed by an open label multicenter study | Oral rucaparib | Antitumour activity, safety | TTP, OS | Dec 2007–Jan 2015 Jan 2015 (primary data) |
| Rucaparib | NCT01891344 ARIEL2 | II | Platinum-sensitive, relapsed high grade epithelial ovarian, fallopian, primary peritoneal cancer. Part 1: received ⩾1 prior platinum-based regimen. Part 2: received ⩾3 prior chemotherapy regimens | Single-arm, open-label two part study | Oral rucaparib | Disease progression (part 1), ORR (part 2) | ORR (part 1), disease progression (part 2), DoR, OS, safety, PK | Sep 2013-Mar 2017 Mar 2017 (primary data) |
| Rucaparib | NCT01482715 | I/II | High grade, measurable disease relapsed gBRCAm OC following ≥3 prior chemotherapy regimens, or have advanced solid tumour | Single-arm, open-label dose finding study | Oral rucaparib | Safety, PK, ORR | DoR, OS, safety | Nov 2011- Apr 2017 Apr 2017 (primary data) |
| Rucaparib | NCT01968213 ARIEL3 | III | Platinum-sensitive relapsed gBRCAm HGSOC or endometrial, primeary peritoneal, or fallopian tube cancer | Randomised double-blind, placebo-controlled, parallel-group | Oral rucaparib, placebo | PFS | OS, PRO, safety, PK | Jan 2014-Mar 2017 2016 Mar 2017 (primary data) |
| Talazoparib | NCT02326844 | II | Recurrent, gBRCAm OC following progression on prior PARP inhibitor therapy | Single-arm, open-label | Oral talazoparib | ORR | Safety | Dec 2014-Dec 2016 Sept 2016 (primary data) |
| Talazoparib | NCT01989546 | I/II | gBRCAm OC, primary peritoneal, breast, or other solid tumours following progression on standard therapy or who have no acceptable standard treatment options | Single-arm open-label | Oral talazoparib | PD effect | Nov 2013-Mar 2017 Mar 2017 (primary data) | |
| Veliparib | NCT01472783 | I/II | gBRCAm platinum-resistant or partially platinum-sensitive relapsed epithelial OC | Single-arm, open-label | Oral veliparib | MTD, response rate | PFS, OS | Nov 2011-Aug 2016 Jan 2016 (primary data) |
| Veliparib | NCT01540565 | II | gBRCAm recurrent or persistent epithelial ovarian, fallopian tube, or primary pertioneal cancer | Single-arm open-label | Oral veliparib | Safety, objective tumour response, safety | PFS, OS | Apr 2012-Apr 2017 April 2017 (primary data) |
| Veliparib | NCT02470585 | III | Newly diagnoses Stage III or IV HGSOC, fallopian tube, or primary peritoneal carcinoma | Randomised, double-blind, three-arm, parallel group | Oral veliparib, carboplatin, paclitaxel, placebo | PFS | OS, tdisease related symptom score | July 2015 Jan 2019 Jan 2019 (primary data) |
|
Combination therapy trials | ||||||||
| Niraparib + bevacizumab | NCT02354131 AVANOVA1 | I/II | Recurrent, HRD platinum sensitive HGSOC, fallopian tube, or peritoneal cancer | Randomised open-label, parallel group | Oral niraparib and/or oral niraparib + bevacizumab IV vs bevacizumab IV alone | PFS | Disease control rate | Feb 2015-Dec 2019 Nov 2017 (primary data) |
| Olaparib + cediranib | NCT01116648 | I/II | Recurrent papillary serous OC, fallopian tube, or peritoneal cancer of for recurrent TNBC | Randomised open-label, parallel group | Oral olaparib + oral cediranib or oral olaparib | MTD, DLT, PFS | OS, tumour response rate, CBR, safety | Mar 2010-Feb 2016 Feb 2016 (primary data) |
| Olaparib +AZD2014 or AZD5363 | NCT02208375 | I/II | Recurrent endometrial, OC, or TNBC | Non-randomised, open-label, parallel group | Oral olaparib + oral AZD2014 or oral olaparib + oral AZD5363 | MTD | Disease response and biomarker response | Nov 2014-Nov 2020 Nov 2020 (primary data) |
| Olaparib + BKM120 or BYL719 | NCT01623349 | I | Recurrent HGSOC or TNBC | Non-randomised, open-label | Oral olaparib + oral BKM120 or oral olaparib + BYL719 | MTD, RP2D | Safety, PK | Sept 2012-Dec 2016 Aug 2016 (primary data) |
| Olaparib + cisplatin, paclitaxel, bevacizumab | NCT02121990 | I | Newly diagnosed optimally debulked OC, primaryperitoneal, and fallopian tube cancer | Single arm, open-label | Oral olaparib + IP cisplatin, IV/IP paclitaxel, IV bevacizumab | MTD | Toxicity | Apr 2014- Apr 2017 Apr 2017 (primary data) |
| Olaparib + carboplatin + paciltaxel | NCT01650376 | I/II | Relapsed OC or uterine cancer | Single arm, open label, safety study | Oral olaparib + IV carboplatin + IV paciltaxel | DLT | Safety, OS, response to therapy, TTP | Aug 2012–Dec 2017 Dec 2016 (primary data) |
| Olaparib + cediranib maleate | NCT02446600 | III | Recurrent platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer | Randomised, comparative, open label, parallel group | Carboplatin + paclitaxel or carboplatin + gemcitabine hydrochloride or carboplatin + liposomal hyrdocholride or olaparib or olaparib +cediranib maleate | PFS | OS, safety, PRO | Feb 2016–Dec 2019 Dec 2019 (primary data) |
| Olaparib + cediranib maleate | NCT02502266 | II/III | Recurrent platinum-resistant or -refractory ovarian, fallopian tube, or primary peritoneal cancer | Randomised, comparative, open label, parallel group | Physician choice standard of care with eith paclitaxel or toptecan hydrocholoride or olaparib + cediranib maleate or cediranib maleat or olaparib | OS (phase III); PFS (phase II) | Safety, ORR, PRO | Feb 2016–Jun 2023 Jun 2023 (primary data) |
| Olaparib + carboplatin + paclitaxel | NCT01081951 | II | Platinum-sensitive advanced serious ovarian cancer | Randomised open-label, parallel group | Oral olaparib + IV carboplatin + IV paclitaxel or IV paclitaxel + IV carboplatin | PFS | OS. Percentage change in tumour size | Feb 2010–Dec 2016 Oct 2011 (primary data) |
| Talazoparib | NCT02627430 | I | Metastatic advanced solid tumour or recurrent ovarian, fallopian tube, primary peritoneal, or TNBC | Open label, single arm | Talazoparib and AT13387 (HSP90 inhibitor) | MTD | Adverse events, PK | Mar 2016-Mar 2019 Mar 2019 (primary data) |
| Veliparib + topotecan | NCT01690598 | I/II | Platinum-sensitive relapsed epithelial OC, primary fallopian or primary peritoneal cancer | Single-arm, open-label | Oral veliparib + topotecan IV | MTD, ORR | PFS, OS | Nov 2012-Feb 2015 Jan 2015 (primary data) |
| Veliparib + paclitaxel + carboplatin + bevacizumab | NCT00989651 | I | Newly diagnosed, stage II-IV epithelial OC, fallopian tube or primary peritoneal cancer | Single-arm, open-label | Oral veliparib + paclitaxel IV, carboplatin IV, bevacizumab IV | DLT | Objective tumour response, PFS, safety | Oct 2009-Sep 2020 Sep 2020 (primary data) |
| Veliparib + PLD + carboplatin + bevacizumab | NCT01459380 | I | Recurrent, platinum- sensitive OC, primary peritoneal or fallopian tube cancer | Randomised open-label, parallel group | Oral veliparib + PLD IV + carboplatin IV + bevacizumab IV | DLT, safety | ORRl | Oct 2011- Aug 2016 Aug 2016 (primary data) |
| Veliparib + carboplatin +paclitaxel | NCT02470585 | III | Newly diagnosed stage III or IV HGSOC, fallopian tube, or primary peritoneal cancer | Randomiseddouble blind, parallel group | Oral veliparib, IV carboplatin, and IV paclitaxel or IV carboplatin + IV paclitaxel + placebo | PFS, | OS, disease related symptom score | July 2015- Jan 2019 Jan 2019 (primary data) |
| Veliparib + temozolomide | NCT01113957 | II | Recurrent high grade serous ovarian cancer | Randomised open label, parallel group | Oral veliparib + temoxolomide or PLD | ORR | PFS, TTP, OS, safety, QoL | Mar 2010-June 2013 Jun 2013 (primary data) |
| Veliparib + cyclophosphamide | NCT01306032 | II | Refractory BRCA-positive ovarian, primary peritoneal, or HGSOC, fallopian tube cancer, TNBC, and low-gread non-Hodgkin's lymphoma | Randomised, open label, cross-over | Oral veliparib and oral cyclophosphamide or cyclophosphamide | ORR, PFS | Safety | Jan 2011-Dec 2014 Dec 2014 (primary data) |
Abbreviations: CBR=clinical benefit rate; DDFS=distant disease-free survival; DLT=dose-limiting toxicities; DoR=duration of response; gBRCAm=germline BRCA mutation; HER2=human epidermal growth factor receptor 2; HGSOC=high-grade serous OC; HRD=homologous recombination deficiency; IDFS=invasive disease-free survival; IP=intraperitoneal; IV=intravenous; MTD=maximum tolerated dose; ORR=overall response rate; OS=overall survival; PARP=poly(ADP-ribose) polymerase; PD=pharmacodynamic; PFS=progression-free survival; PK=pharmacokinetic; PLD=pegylated liposomal doxorubicin; PRO=patient-reported outcomes; QoL=quality of life; RP2D=recommended phase II dose; TNBC=triple-negative breast cancer; TTP=time to progression.
Source: clinicaltrials.gov.