. 2018 Jul 30;8(16):4279–4294. doi: 10.7150/thno.26345

Table 2.

Registered clinical studies using nanoparticles in ovarian cancer.

Study title	ClinicalTrials.gov identifier (phase)	Commentary
Intraperitoneal Aerosolisation of Albumin-stabilized Paclitaxel Nanoparticles for Recurrent GI and Ovarian Cancer	NCT03304210 (Phase I, II)	Pressurized intraperitoneal (IP) aerosol therapy (PIPAC) is a new technological solution for the administration of IP chemotherapy, which allows repeated laparoscopy aided aerosol delivery of anticancer drugs to the peritoneal cavity. Nab (nanoparticle albumin-bound) technology is suitable for encapsulation of other drugs (rapamycin, docetaxel).
Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer	NCT00499252 (Phase II)	Weekly nab-paclitaxel had noteworthy single-agent activity and was tolerable in this cohort of platinum- and taxane- resistant ovarian cancer patients. The median PFS was 4.5 months and OS was 17.4 months. The investigators concluded that these parameters are quite notable since 70% of the study population had recurred within 3 months of primary treatment completion ¹⁰⁵.
Study of Paclitaxel in Patients With Ovarian Cancer	NCT00989131 (Phase III)	The purpose was to compare the efficacy and safety of paclitaxel micellar nanoparticle formulation (Paclical®) and paclitaxel with Cremophor EL used as the solubilizer (Taxol®). In results Paclical® showed a positive risk/benefit profile compared to treatment with Taxol®; i.e. no need for pre-medication, the infusion time is one hour and possibly a reduced risk of experiencing neuropathy.
Intraperitoneal Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced Cancer of the Peritoneal Cavity	NCT00825201 (Phase I)
Sargramostim and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer That Did Not Respond to Previous Chemotherapy	NCT00466960 (Phase II)	Patients received Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) subcutaneously in combination with nab-paclitaxel. This combination demonstrated biochemical responses in a majority of patients, although did not demonstrate an advantage in OS over prior studies of nab-paclitaxel monotherapy ¹²⁸.
Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Bevacizumab in Treating Patients With Stage IV Melanoma That Cannot Be Removed by Surgery or Gynecological Cancers	NCT02020707 (Phase I)	The approach of combining targeted antiangiogenic agents with cytotoxic drugs may lead to more effective use of antiangiogenic drugs in the clinic.
Study to Evaluate CORT125134 in Combination With Nab-paclitaxel in Patients With Solid Tumors	NCT02762981 (Pase I, II)	Recent studies showed that glucocorticoid receptor (GR) activation increases resistance to chemotherapy in high-grade serous ovarian cancer. The GR-selective nonsteroidal antagonist, CORT125134, inhibits the tumor cell survival effect of GR activation and improves sensitivity to chemotherapy ¹²⁹.
Pharmacokinetic, Safety and Efficacy Study of Nanoparticle Paclitaxel in Patients With Peritoneal Cancers	NCT00666991 (Phase I)	Compared to IV paclitaxel administration, IP administration of nab-paclitaxel provides higher and prolonged peritoneal paclitaxel levels with minimal systemic exposure and reduced toxicity ¹⁰².
Lapatinib and Paclitaxel in Treating Patients With Advanced Solid Tumors	NCT00313599 (Phase I)	Brief high doses of lapatinib (tyrosine kinase inhibitor targeting the Human Epidermal Growth Factor Receptor (HER) family) given prior to weekly nab-paclitaxel is a feasible and tolerable clinical regimen. Lapatinib may be a novel approach to improving chemotherapeutic delivery through vascular-priming chemosensitization ¹³⁰.
Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With mTOR Mutations	NCT02646319 (Phase II)	Rapamycin present immunosuppressant and potential antiangiogenic and antineoplastic activities ¹³¹. The binding of water-insoluble rapamycin to nanoparticle albumin permits the albumin-mediated endocytosis of rapamycin by tumor cells and endothelial cells.
TKM 080301 for Primary or Secondary Liver Cancer	NCT01437007 (Phase I)	This phase I trial evaluates feasibility of administering TKM-080301 via Hepatic Arterial Infusion (HAI) and to characterize the pharmacokinetics and pharmacodynamics of TKM-080301 administered by HAI.
CRLX101 in Combination With Bevacizumab for Recurrent Ovarian/Tubal/Peritoneal Cancer	NCT01652079 (Phase II)	Some preclinical studies have shown that combining antiangiogenic therapy with strategies that inhibit tumor hypoxia and expression of hypoxia-inducible factors (i.e. CRLX101) can lead to improved anticancer efficacy. Therefore, it has been hypothesized that the combination of bevacizumab with CRLX101 might have unique clinical activity ¹³². Preliminary data from clinical studies of CRLX101 in patients with platinum-resistant ovarian cancer suggest that this agent can result in net tumor reductions ¹³³.
IMX-110 in Patients With Advanced Solid Tumors	NCT03382340 (Phase I, II)	IMX-110 is a multi-compound nanoparticle which co-deliver low-dose doxorubicin with anti-resistance agents (Stat3/NF-kB/poly-tyrosine kinase inhibitor), to disrupt key resistance pathways ¹³⁴.
A Study of BIND-014 Given to Patients With Advanced or Metastatic Cancer	NCT01300533 (Phase I)	BIND-014 was generally well tolerated, with predictable and manageable toxicity and a unique pharmacokinetic profile compared with conventional docetaxel ¹³⁵.
Safety Study of CALAA-01 to Treat Solid Tumor Cancer	NCT00689065 (Phase I)	CALAA-01 is the first targeted, polymer-based nanoparticle-carrying siRNA that entered clinical trials for cancer. Results of this Phase I clinical trial demonstrate that the siRNA delivered via the targeted NPs can engage the RNAi machinery in humans and that siRNA can be used as a gene-specific therapy ¹⁰⁶.