Paclitaxel (Albumin-bound) and Oxaliplatin for Advanced Hepatobiliary and Malignant Tumors
Status:
Not yet recruiting
Trial end date:
2023-10-20
Target enrollment:
Participant gender:
Summary
1. Advantages of albumin-bound paclitaxel Paclitaxel for injection (albumin-binding type)
uses human serum albumin (HAS) as a carrier, and paclitaxel and HSA are made into
paclitaxel-bound albumin nanoparticles by a high-pressure homogenization technique. After
injection of paclitaxel (albumin-binding) into the blood, it rapidly disintegrates and
disperses into a smaller albumin-paclitaxel complex, which binds and activates the gp60
albumin receptor on vascular endothelial cells, interacts with Caveolin on the cell membrane,
and then is transported to the tumor intercellular substance by transcytosis. Tumor cells can
secrete a SPARC protein with a specific affinity for albumin, which actively captures the
albumin-paclitaxel complex in the tumor stroma and accumulates around the tumor cells. Since
tumor neovascular endothelial cells highly express gp60 receptor and the SPARC protein is
also highly expressed in the tumor region, the special transport mechanism of "gp60- Caveolin
/ caveola -SPARC protein" makes the paclitaxel for injection (albumin binding) have unique
targeting and penetrating properties toward tumor tissues, hence the drug is highly
concentrated in the tumor tissue, which can better increase the therapeutic effect and reduce
the damage to normal tissues.
Paclitaxel for injection (albumin-binding type) has the following advantages: (1) it is
unnecessary to pre-administer anti-allergic drugs, the infusion time is within 30 min, and
patients have good compliance; (2) due to its higher safety, the dosage can be given as high
as 260-300 mg/m2; (3) it makes full use of gp60 / cysteine acid secretory protein (SPARC
protein) channel to make the drug enrich toward the tumor area, and the effect is good; (4)
as the dosage is within 80 ~ 300 mg/m2, the AUC increase proportionally with the administered
dose, ]the body is linearly metabolized., the half-life period does not prolong with the
dose, and the clinical medication is safe and controllable. Currently, the drug has been
approved for breast cancer treatment in China; approved by the US Food and Drug
Administration (FDA) for breast cancer, lung cancer, and pancreatic cancer treatment;
approved for gastric cancer treatment in Japan; and NCCN guidelines recommend it for the
treatment of intrahepatic cholangiocarcinoma, melanoma, ovarian cancer, and cervical cancer.
In summary, based on the biological advantages of albumin-binding paclitaxel such as
high-distribution, high-dose, high-efficiency, and low-toxicity, the reported good clinical
benefit and safety for hepatobiliary and malignant tumors, and the limited data about
albumin-bound paclitaxel + oxaliplatin as the first-line treatment for advanced hepatobiliary
and pancreatic malignancies, especially in Chinese patients, our center believes that is
feasible and necessary to explore the effectiveness and safety of paclitaxel for injection
(albumin-binding) combined with oxaliplatin as the first-line drugs for treatment of advanced
oxaliplatin-based malignant tumors.
2 Purposes To evaluate the efficacy and safety of paclitaxel (albumin-bound) combined with
oxaliplatin as the first-line drugs for treatment of advanced hepatobiliary and malignant
tumors.
Primary endpoint: progression-free survival (PFS) Secondary study endpoints: disease control
rate (DCR), overall survival (OS), and incidence and severity of adverse events (AE).
3 Research plan 3.1 Research Design This study was a single-center, one-arm, phase II/III
clinical trial, which plans to recruit 57 patients.