pegylated liposomal doxorubicin

P1, N=93, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2024 --> Jun 2027 | Trial primary completion date: Jun 2024 --> Jun 2025

P2, N=60, Not yet recruiting, Chinese PLA General Hospital

Based on the previous studies on the doxorubicin (DOX) formulation for cancer targeting therapy, we developed a novel DOX delivery formulation for the targeting chemotherapy of HCC and DOX resistant HCC...Based on the above, an HCC targeting and MDR inhibiting DOX delivery liposomal formulation, HCSP4/Lipo-DOX/miR125a-5p was synthesized and tested for its HCC therapeutic efficacy in vitro...The potential therapeutic mechanism of the DOX delivery formulation was explored, and the formulation inhibited the expression of MDR-relevant genes including ATP-binding cassette subfamily B member 1 (ABCB1, also known as P-glycoprotein), ATP-binding cassette subfamily C member 5 (ABCC5), enhancer of zeste homolog 2 (EZH2), and ATPase Na+/K+ transporting subunit beta 1 (ATP1B1). Our study presents a novel targeting chemotherapeutic drug formulation for the therapy of HCC, especially for drug resistant HCC, although it is primarily and needs further study in vivo, but provided a new strategy for the development of novel anticancer drugs.

P1, N=24, Recruiting, Case Comprehensive Cancer Center | Trial completion date: May 2024 --> Nov 2024 | Trial primary completion date: Apr 2024 --> Oct 2024

P1/2, N=72, Recruiting, Sham Sunder Kakar | Not yet recruiting --> Recruiting | Trial primary completion date: Nov 2025 --> Nov 2026

Nanotechnology has the potential to provide formulations of antitumor agents with increased selectivity towards cancer tissue thereby decreasing systemic toxicity. In the case of LipoDOX, autophagy and apoptosis were still detectable, whereas PLGADOX induced only detectable mitochondrial toxicity. Cardiotoxic effects were frequently sex-related with the greater risk of cardiotoxicity observed mostly in male rats.

P3, N=448, Recruiting, Mural Oncology, Inc | Active, not recruiting --> Recruiting | Trial completion date: Dec 2026 --> May 2027 | Trial primary completion date: Dec 2025 --> May 2026

P2/3, N=600, Recruiting, Sutro Biopharma, Inc. | Phase classification: P2 --> P2/3 | N=140 --> 600

P3, N=186, Recruiting, Genelux Corporation | Trial primary completion date: Aug 2024 --> Aug 2025

Rat glioma cells and rodent glioma models were treated with ibrutinib alone (1-10 µM and 25 mg/kg) and in combination with doxil (10-100 µM and 3 mg/kg) to assess additive effects on viability, drug concentrations, tumor volume, endothelial junctional expression and survival. These findings indicate ibrutinib's ability to increase brain endothelial permeability via junctional disruption and efflux inhibition, to increase BTB drug entry and prolong rodent glioma model survival. Our results motivate the need to identify other BTB modifiers, all with the intent of improving survival and reducing systemic toxicities.

P1, N=40, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1/2, N=10, Terminated, Pfizer | Active, not recruiting --> Terminated; A business decision was made by Pfizer to terminate and remove the Phase 2 expansion of this study for administrative reasons. The reason for study termination is not due to any safety concerns or requests from regulatory authorities.

P3, N=1200, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

In this study, we investigated whether mEHT accelerates the tumor-specific delivery of doxorubicin (DOX) from lyso-thermosensitive liposomal doxorubicin (LTLD) and improves its anticancer efficacy in mice bearing a triple-negative breast cancer cell line (4T1)...The body weight loss was similar in all mice treated with any DOX formulation, suggesting no difference in toxicity. In conclusion, LTLD combined with mEHT represents a novel approach for DOX delivery into cancer tissue.

P2/3, N=650, Recruiting, Daiichi Sankyo | Not yet recruiting --> Recruiting

As a result, blood vessel functionality is enhanced, leading to increased infiltration by 40 % of immune cells (CD4+ and CD8+ T-cells) and improving the antitumor efficacy of Doxil nanomedicine and anti-PD-1 immunotherapy. In conclusion, our research underscores the unique and synergistic potential of combining mechanotherapeutics and sonopermeation. Both approaches are undergoing clinical trials to enhance cancer therapy and have the potential to significantly improve nano-immunotherapy in sarcomas.

These results indicated that rbNPs are promising nanoparticles, hold significant potential for anti-cancer applications, and are expected to play a vital role in cancer treatment.

Histoplasty is a non-ablative focused ultrasound approach to non-invasively modify the tumor ECM, increase chemotherapeutic uptake, and alter the tumor immune microenvironment.

P3, N=1200, Not yet recruiting, Merck Sharp & Dohme LLC

P3, N=376, Active, not recruiting, Mural Oncology, Inc | Recruiting --> Active, not recruiting

In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD (30-35 mg/m2) and cyclophosphamide (600 mg/m2), followed by four cycles of taxanes (docetaxel, 90-100 mg/m2 or nab-paclitaxel, 260 mg/m2), concomitant with eight cycles of trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) every 3 weeks. This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile, especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.

P=N/A, N=18, Recruiting, The University of Hong Kong

P3, N=800, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P2, N=48, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P1, N=33, Recruiting, Medical College of Wisconsin | Trial completion date: May 2028 --> May 2026 | Trial primary completion date: May 2027 --> May 2026

P2, N=146, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Jun 2026 --> May 2024

P3, N=358, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=36, Recruiting, Medical College of Wisconsin | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2024 --> Jan 2025

P1/2, N=16, Terminated, THERAPIM PTY LTD | Phase classification: P1b/2a --> P1/2 | N=78 --> 16 | Trial completion date: Mar 2025 --> Nov 2023 | Recruiting --> Terminated | Trial primary completion date: Mar 2025 --> Nov 2023; For technical reasons, it was decided by the sponsor to close the ongoing ovarian cancer study, AM ATX101-03, immediately.

P1/2, N=264, Completed, ImmunoGen, Inc. | Phase classification: P1b/2 --> P1/2

P2, N=82, Completed, Oslo University Hospital | Active, not recruiting --> Completed

Standard therapy comprised an investigator-selected carboplatin doublet (paclitaxel, gemcitabine or pegylated liposomal doxorubicin [PLD]) for 6 cycles, followed by maintenance niraparib in patients with a complete or partial response or stable disease. Conclusion The apparent difference in atezolizumab treatment effect according to investigator-selected chemotherapy doublet, including more favourable outcomes with atezolizumab in the gemcitabine subgroup, may be attributable to selection bias towards gemcitabine in poorer-prognosis patients and the small sample sizes of the paclitaxel and gemcitabine subgroups. Ongoing translational work may reveal further differences and hypotheses.

Trabectedin did not improve median OS and showed a worse safety profile in comparison with physician's choice control chemotherapy.

P2, N=350, Active, not recruiting, Actuate Therapeutics Inc. | Recruiting --> Active, not recruiting

The addition of ipi/nivo to chemotherapy increased toxicity without improving efficacy. Ipi/nivo administered sequentially to chemotherapy was tolerable and induced clinical responses.

P2, N=136, Recruiting, AGO Research GmbH | Trial completion date: Dec 2023 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2025

The MITO39 study showed a statistically significant difference in terms of PFS, suggesting that previous exposure to PARPi might inhibit the efficacy of PLD-Trabectedin. Regarding tolerability, no remarkable disparity was noted; PLD-Trabectedin was confirmed to be a well-tolerated scheme in both groups. To our knowledge, these are the first data regarding this topic, which we deem to be of great relevance in the current landscape.

P2, N=149, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Jan 2025 | Trial primary completion date: Dec 2023 --> Jan 2023

Trabectedin combined with PLD significantly improves OS and PFS in patients with BRCA-associated and platinum-sensitive recurrent ovarian cancers. The potential use of trabectedin combined with PLD should be selected according to the PFI and BRCA mutation status of patients.

P2, N=198, Not yet recruiting, Yonsei University | Initiation date: Sep 2023 --> Jan 2024

P1, N=30, Recruiting, Swiss Group for Clinical Cancer Research

P1, N=87, Terminated, Atreca, Inc. | Phase classification: P1b --> P1 | N=240 --> 87 | Trial completion date: Mar 2025 --> Nov 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Nov 2023; Sponsor Decision