doxorubicin liposomal

P2/3, N=488, Suspended, National Cancer Institute (NCI) | Trial completion date: Jun 2023 --> Jul 2027 | Recruiting --> Suspended

Nano-immunotherapy regimens have high potential to improve patient outcomes, as already demonstrated in advanced triple negative breast cancer with nanoparticle albumin-bound paclitaxel and the immune checkpoint blocker (ICB) atezolizumab. Indeed, when combining tranilast with Doxil and ICBs, synergistic effects on efficacy, with all mice cured in one of the two ICB-insensitive tumor models investigated is resulted. These results suggest that strategies to treat breast cancer with nano-immunotherapy should also include a mechanotherapeutic to decompress vessels.

A 46-year-old man had been diagnosed with HIV infection and treated with combination antiretroviral therapy of dolutegravir/abacavir/lamivudine (Triumeq) for one year. The plasma Kaposi sarcoma herpesvirus viral load was 365,000 copies/mL. During hospitalization, progressive pancytopenia and spiking fever persisted, and he died of multi-organ failure before completion of chemotherapeutic treatments with rituximab plus liposomal doxorubicin.

P2, N=164, Not yet recruiting, National Cancer Institute (NCI)

The combination treatment led to trigger immunogenic tumor apoptosis, and enhance antitumor immunity, therefore, improved anti-tumor efficiency, and further prolonged survival duration. The combination of liposomal silybin and liposomal doxorubicin might be a new chemo-immunotherapy approach for triple negative breast cancer (TNBC) tumor treatment.

Compared to PAD, RAD induction had comparable efficacy and a significantly better safety profile, improved quality of life for patients, and reduced occupational stress for doctors. However, RAD induction may need to be limited to four cycles to avoid irreversible damage to hematopoietic stem cells.

P2, N=95, Active, not recruiting, AstraZeneca | Trial completion date: Mar 2021 --> Nov 2021

P1, N=214, Active, not recruiting, Arcus Biosciences, Inc. | Recruiting --> Active, not recruiting

P3, N=326, Not yet recruiting, Novartis Pharmaceuticals

P3, N=614, Active, not recruiting, ARCAGY/ GINECO GROUP | Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Jun 2021 --> Oct 2021

P2, N=136, Not yet recruiting, AGO Research GmbH | Initiation date: Jul 2020 --> Jul 2021

Our results indicate that this "double-attack" strategy using CD20 Ab-mPEG scFv and PLD can retain the tumor targeting (first attack) and confer PLD tumor-selectivity (second attack) to enhance PLD internalization and improve therapeutic efficacy in liquid tumors.

The GeparOcto randomized clinical trial compared the efficacy of 2 neoadjuvant breast cancer (BC) treatment regimens: sequential intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) vs weekly paclitaxel and nonpegylated liposomal doxorubicin (PM) in patients with different biological BC subtypes. Patients with triple-negative BC (TNBC) randomized to the PM arm received additional carboplatin (PMCb)...The elevated pCR rate in BRCA1/2-mutated ERBB2-negative, hormone receptor-positive BC suggests that germline BRCA1/2 testing should be considered prior to treatment start. ClinicalTrials.gov Identifier: NCT02125344.

Olaparib resulted in statistically significant and clinically relevant improvements in ORR and PFS compared with nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy.

In vivo results showed that ER-lip promoted survival and reduced tumor growth rate in animal model compared to Caelyx®. In conclusion these results suggested that the ER-lip could be served as promising formulation for the treatment of cancers with the high expression of EpCAM.

P1, N=80, Recruiting, Hoffmann-La Roche | N=60 --> 80

P3, N=427, Recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

As many comparable options exist for SLT and as brentuximab vedotin (BV) is increasingly used in the front-line setting, we report the results of pts who had an AHCT after a novel anti-PD-1-based salvage regimen, pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin (pembro-GVD, NCT03618550)...Pts who achieved CR by PET (Deauville ≤3) after 2 or 4 cycles proceeded to carmustine, etoposide, cytarabine, and melphalan (BEAM) + AHCT...Stem cells were mobilized with G-CSF and plerixafor for all except 1 pt who received G-CSF alone with a median of 19.68 x10^6 CD34+ cells/kg (range 5.26-59.83) collected during 1 day of pheresis for all pts... BEAM/AHCT after SLT with pembro-GVD may be complicated by steroid responsive immune related adverse events, but is an extremely effective treatment for RR cHL with high response rates and no relapses to date.

Here, we report the probability of starting second-line study chemotherapy in the Stop&Go trial, and the progression-free survival (PFS) and overall survival (OS) of patients who received both the first- and second-line treatment in an intermittent versus continuous schedule. First-line chemotherapy comprised paclitaxel plus bevacizumab, second-line capecitabine or non-pegylated liposomal doxorubicin, given per treatment line as two times four cycles (intermittent) or as eight consecutive cycles (continuous). Of the 420 patients who started first-line treatment within the Stop&Go trial (210:210), a total of 270 patients continued on second-line study treatment (64% of all), which consisted of capecitabine in 201 patients and of non-pegylated liposomal doxorubicin in 69 patients, evenly distributed between the treatment arms. Second-line PFS was positively influenced by prior hormonal therapy for metastatic disease and longer first-line PFS duration, while triple-negative tumor status had a negative influence. Patients with a shorter time to progression (TTP) in first-line (≤10 months) had a higher probability of starting second-line treatment if they received intermittent compared to continuous chemotherapy (OR 1.97; 95% CI: 1.02-3.80). We recommend continuous scheduling of both the first- and second-line chemotherapy for advanced breast cancer.

In 2009, results from the pivotal trial OVA-301 led the European Medicines Agency (EMA) to the approval of trabectedin in combination with PEGylated liposomal doxorubicin for the treatment of platinum-sensitive recurrent OC; further studies revealed an additional benefit also in the subgroup of patients with partially platinum-sensitive disease and in those with a BRCA-mutated status. Additionally, trabectedin demonstrated to prolong the time interval to the subsequent chemotherapy line. Recently, the improved understanding of the antitumor action exerted by trabectedin paved the way to new investigational trials exploring its combination with targeted therapies.

Patients who are not considered suitable for platinum-based chemotherapy are treated with a platinum-free regimen such as weekly paclitaxel, pegylated liposomal doxorubicin (PLD), gemcitabine, or topotecan. Treatment for the patient subgroup which is considered suitable for platinum-based therapy but cannot receive carboplatin due to uncontrollable hypersensitivity reactions may consist of trabectedin and PLD...Clinical studies have also shown the efficacy of angiogenesis inhibitors such as bevacizumab and the PARP inhibitors olaparib, niraparib and rucaparib...The PARP inhibitors niraparib, olaparib and rucaparib have already been approved for use by the FDA and the EMA. The presence of a BRCA mutation is a predictive factor for a better response to PARP inhibitors.

This non-interventional, prospective study, conducted in 57 reference sites across Europe, consistently confirms that trabectedin plus pegylated liposomal doxorubicin (PLD) in routine clinical practice represents clinically meaningful and safe option for women with platinum-sensitive recurrent ovarian cancer. Although our study population represented a heterogeneous, older and more pretreated population than those in prospective clinical trials, the combination of trabectedin plus PLD induced comparable clinical benefits, with a similar and manageable safety profile. Overall, our findings support that trabectedin in combination with PLD maintains antitumor activity when administered to heavily pretreated patients in real-life clinical practice.

P2/3, N=488, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2027 --> Jun 2023 | Trial primary completion date: Jul 2027 --> Jun 2023

P2, N=119, Ongoing, FONDAZIONE IRCCS "ISTITUTO NAZIONALE DEI TUMORI"

No significant influence of NPLD on T-DM1 pharmacokinetics was observed. The addition of NPLD to T-DM1 is feasible but does not seem to improve the antitumor efficacy of T-DM1 in HER2+ MBC patients.

P3, N=427, Ongoing, FONDAZIONE POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI IRCCS UNIVERSITA' CATTOLICA DEL SACRO CUORE

Therefore, the results of this study can exhibit that specific recognition and binding of antibodies with CD133 receptors on HT-29 cells can result in enhanced cellular uptake, internalization and cytotoxicity. The research suggests further investigation for in vivo studies and may offer proof-of-principle for an active targeting concept.

This is to be achieved by combining Lyso-Thermosensitive Liposomal Doxorubicin (LTLD, ThermoDox, Celsion Corporation, Lawrenceville, NJ, USA) with mild local hyperthermia, induced by Magnetic Resonance guided High Intensity Focused Ultrasound (MR-HIFU). Results will be published in an academic peer-reviewed journal. NCT03749850, EudraCT 2015-005582-23.

The association of Lynch syndrome with hematological cancer is known, as well as the increased risk of cancer after bone marrow transplantation. However, a patient with Lynch syndrome and a diagnosis of breast tumor a few months after bone marrow transplantation was never reported. We describe the patient's difficult management and reinforce the importance of investigating hereditary syndromes for genetic counseling, early screening, as well as timely diagnosis and treatment.

This effect was also more pronounced with a liposomal P5 and Doxil® compared with free peptide and doxorubicin. In conclusion, the results demonstrated that Doxil® plus liposomal P5 could have a decreasing effect on MDSCs and tumor growth, and it could be beneficial in breast cancer treatment.

The RP2D is 200 mg veliparib BID on days 1-14 with 40 mg/m PLD on day 1 of a 28-day cycle. Anti-tumor activity was seen in both strata. However, given development of long-term squamous cell cancers and the PK interaction observed, efforts should focus on other targeted combinations to improve efficacy.

P1/2, N=31, Active, not recruiting, National Cancer Centre, Singapore

P3, N=414, Recruiting, Grupo Español de Investigación en Cáncer de Ovario | Trial completion date: Nov 2023 --> May 2024 | Trial primary completion date: May 2023 --> Nov 2023

P1b, N=15, Recruiting, Shaare Zedek Medical Center | Trial completion date: Jun 2020 --> Jun 2021 | Trial primary completion date: Mar 2020 --> Apr 2021

Our data suggested that angiotensin-converting enzyme inhibitors and dexrazoxane plus epirubicin were the most effective interventions for preventing cardiotoxicity and CHF. However, ACEIs plus doxorubicin was the best treatment for preventing LVEF reduction.

This case illustrates varying and overlapping presentations of KSHV infection in immunocompromised patient. Therapy does not exist and KS could not be treated due to the poor condition of patients. Patients have a high mortality rate and often misdiagnosed.

P1, N=60, Recruiting, Hoffmann-La Roche

P1b/2, N=53, Active, not recruiting, Aravive, Inc. | Recruiting --> Active, not recruiting | N=196 --> 53

P2, N=200, Recruiting, Spanish Breast Cancer Research Group | Not yet recruiting --> Recruiting

"ARv/PLD combination was safe and tolerated. No DLT was observed. MTD of ARv was 6.5 mg/kg Q3W."

P3, N=566, Active, not recruiting, Pfizer | Trial completion date: Dec 2020 --> Dec 2021