Paclitaxel (Albumin-bound) and Oxaliplatin for Advanced Hepatobiliary and Malignant Tumors
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|ClinicalTrials.gov Identifier: NCT04060472|
Recruitment Status : Not yet recruiting
First Posted : August 19, 2019
Last Update Posted : August 19, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Advanced Hepatobiliary and Malignant Tumors||Drug: albumin-bound paclitaxel + oxaliplatin||Phase 2 Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||57 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Single-center, Single-arm and Phase II/III Clinical Study of Paclitaxel (Albumin-binding) Combined With Oxaliplatin as First-line Treatment for Advanced Hepatobiliary and Malignant Tumors|
|Estimated Study Start Date :||August 20, 2019|
|Estimated Primary Completion Date :||April 20, 2021|
|Estimated Study Completion Date :||October 20, 2023|
|Experimental: albumin-bound paclitaxel + oxaliplatin||
Drug: albumin-bound paclitaxel + oxaliplatin
Using albumin-bound paclitaxel (125 mg/m2, d1, 8, 15, ivgtt) + oxaliplatin (80 mg/m2, d1, 8, ivgtt) with or without other chemotherapeutic drugs, 28 days /cycle, until the disease progresses or patients can not tolerate toxicity. The investigators decide the follow-up treatment plan.
- PFS [ Time Frame: 2 years ]Progression-free surviva
- DCR [ Time Frame: 2 years ]Disease control rate
- OS [ Time Frame: 2 years ]overall survival
- AE [ Time Frame: 2 years ]incidence and severity of adverse events