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OVARIAN CANCER · White paper

Ovarian Cancer Clinical Trials

Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.

Indication overview

About ovarian cancer — and why its trials are hard

Ovarian cancer is the fifth-leading cause of cancer death among women and the most lethal gynecologic malignancy, largely because its non-specific symptoms drive late-stage diagnosis. The median age at diagnosis is about 63, and roughly 10-15% of cases are hereditary, most commonly BRCA1/BRCA2 mutations (also Lynch syndrome). Most tumors are high-grade serous epithelial cancers. The therapeutic backbone remains cytoreductive surgery plus platinum/taxane chemotherapy (carboplatin and paclitaxel), with the anti-angiogenic antibody bevacizumab and, transformatively, PARP inhibitors (olaparib, niraparib, rucaparib) used in maintenance, especially for BRCA-mutated and homologous-recombination-deficient disease. PARP inhibitors markedly extend progression-free survival, though several later-line, non-BRCA indications were voluntarily withdrawn in 2022 after mature overall-survival data raised concerns. Trial design is complicated by high recurrence rates, tumor heterogeneity across subtypes, ascites affecting drug distribution, variable surgical timing, and reliance on surrogate endpoints such as PFS and CA-125 response. Precision-medicine stratification by BRCA/HRD status and adaptive, biomarker-driven designs are central to modern development.

Indication
Ovarian Cancer
ICD-10-CM
C56.9 — Malignant neoplasm of ovary

Approved therapies & pivotal evidence

What's been approved — and by how much it moved the endpoint

Drug (brand)ApprovedSettingPivotal trialPrimary endpointMagnitude of benefit
Carboplatin (Paraplatin) 1989First-line chemotherapy backbone (with paclitaxel) for epithelial ovarian cancerGOG/ICON platinum-taxane trialsOverall survival / progression-free survivalPlatinum-taxane doublet is the established standard-of-care backbone; better tolerated than cisplatin with comparable efficacy
Paclitaxel (Taxol) 1992First-line chemotherapy (with a platinum agent) for advanced ovarian cancerGOG-111 / OV-10Overall survival and response rateAdding paclitaxel to platinum significantly improved survival vs prior cyclophosphamide-based regimens
Bevacizumab (Avastin) 2014Platinum-resistant recurrent disease (2014); later front-line and maintenance (VEGF inhibitor)AURELIA / GOG-0218Progression-free survivalSignificant PFS improvement when added to chemotherapy and continued as maintenance
Olaparib (Lynparza) 2018First-line maintenance in BRCA-mutated advanced ovarian cancer after platinum response (PARP inhibitor; initially approved 2014 for later lines)SOLO-1 (NCT01844986)Progression-free survivalSubstantial PFS benefit; HR ~0.30 vs placebo with a large, durable improvement in median PFS
Niraparib (Zejula) 2020First-line maintenance for advanced ovarian cancer after platinum response regardless of biomarker status (PARP inhibitor; initially 2017 for recurrent)PRIMA (NCT02655016)Progression-free survivalSignificant PFS improvement across the overall population, with greatest benefit in HRD-positive tumors

Where trials have failed

Drugs that missed their endpoint — and what contributed

The most instructive lessons in ovarian cancer development come from programmes that failed the endpoint that mattered.

Drug / trialEndpoint outcomeWhat contributed
Batiraxcept (AXL inhibitor) — NCT04729608Failed to show benefitNo significant difference in median PFS between batiraxcept plus paclitaxel and paclitaxel alone
Motesanib diphosphate (multi-kinase inhibitor) — NCT00574951Trial stopped earlyHalted for severe toxicity raising patient-safety concerns
Idronoxil / phenoxodiol — NCT00382811Ineffective in late-stage diseaseOral phenoxodiol, alone or with weekly carboplatin, was ineffective in late-stage ovarian cancer

Choosing the right endpoint

Primary endpoints that matter in ovarian cancer trials

  • Overall survival (OS) — Gold-standard endpoint but requires long follow-up and can be confounded by post-progression crossover and subsequent therapies
  • Progression-free survival (PFS) — Primary surrogate for most maintenance approvals (bevacizumab, PARP inhibitors); depends on consistent RECIST assessment
  • Objective response rate (ORR) — Useful in treatment (non-maintenance) settings; requires standardized, reproducible tumor measurement
  • CA-125 response (GCIG criteria) — Biomarker of tumor burden for monitoring response and recurrence, but individual variability limits standalone use
  • Quality of life / patient-reported outcomes — Increasingly required to show maintenance therapy benefit is not offset by toxicity

How iNGENū runs ovarian cancer trials

Physician-led design, built for FDA submission

Endpoint & biomarker strategy

Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.

FDA-ready data

Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.

Faster, lower-cost delivery

~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.

PDF
Ovarian Cancer - From Epidemiology to Enhancing Clinical Trial Design
The full white paper: approved-product analyses, pivotal endpoints and trial-design strategy. Open-access · no sign-in.
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Frequently asked questions

Ovarian Cancer clinical trials — FAQs

How have PARP inhibitors changed ovarian cancer treatment?
PARP inhibitors (olaparib, niraparib, rucaparib) exploit synthetic lethality in BRCA-mutated and HRD tumors. Used as maintenance after platinum response, they substantially prolong progression-free survival; olaparib in SOLO-1 (first-line, BRCA-mutated) and niraparib in PRIMA (all-comers) are landmark examples that established maintenance as standard practice.
Why were some PARP inhibitor indications withdrawn in 2022?
Several later-line, heavily pretreated or non-BRCA maintenance indications for PARP inhibitors were voluntarily withdrawn in 2022 after mature overall-survival data from confirmatory trials suggested a potential detriment or failed to confirm benefit, prompting sponsors and the FDA to narrow use toward biomarker-selected populations.
What is the standard first-line treatment for ovarian cancer?
The backbone is maximal cytoreductive (debulking) surgery followed by platinum/taxane chemotherapy, typically carboplatin plus paclitaxel. Depending on stage, BRCA and HRD status, this is followed by maintenance therapy with a PARP inhibitor and/or bevacizumab to delay recurrence.

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