NCT04629781

Open-label Dose Escalation Phase 1b Trial of a New Micellar Docetaxel Compound in Patients With mCRPC

Open-label Dose Escalation Phase 1b Trial of a New Micellar Docetaxel Compound in Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC)

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 11 (actual)
• Sponsor: Swiss Cancer Institute · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Treatment with polysorbate 80-solved Docetaxel (Taxotere®) is hampered by the requirement to co-administer steroids. Chronic (intermittent) steroids are negatively impacting bone health and have well known immunosuppressive effects. Despite steroid premedication, polysorbate 80-solved Docetaxel (Taxotere®) results in occasional infusion reactions due to the solvent polysorbate 80. Docetaxel micellar is a promising alternative to polysorbate 80-solved Docetaxel (Taxotere) as it avoids the mandatory need for steroid administration pre and post infusion, and thus avoids immunosuppressive and bone-damaging effects. There is an unmet medical need to develop steroid-free taxane regimens for patients with advanced cancer to avoid the need for steroid administration pre and post infusion (as outlined above). The unique Docetaxel micellar formulation suggests an improved safety profile compared to polysorbate 80-solved Docetaxel (Taxotere®).

Detailed description

Docetaxel, a semi-synthetic analogue of paclitaxel, is one of the most widely used human anti-cancer agents. Docetaxel and paclitaxel belong to a group of cytotoxic agents called taxanes. Docetaxel has been marketed worldwide by Sanofi-Aventis under the trade name Taxotere® and its use is approved for different types of solid tumors. The efficacy of docetaxel has been proven in two different phase 3 trials in metastatic castration resistant prostate cancer (mCRPC) and is a standard of care option for patients with prostate cancer. In Taxotere®, polysorbate 80 is used as surfactant. Fluid retention and hypersensitivity reactions are reported, and the patients are pre-treated with corticosteroids, e.g. dexamethasone, to avoid or at least reduce the frequency and the severity of both hypersensitivity reactions and fluid retention. Oasmia Pharmaceutical AB (Uppsala, Sweden) has developed a novel formulation of docetaxel (Docetaxel micellar) with N-(all-trans-retinoyl)-L-cysteic acid methyl ester sodium salt (XMeNa) as excipient, thus reducing adverse reactions caused by polysorbate 80. XMeNa forms micelles into which docetaxel can be incorporated thus increasing its aqueous solubility and keeping it dissolved. Rational Treatment with polysorbate 80-solved Docetaxel (Taxotere) is hampered by the requirement to co-administer steroid pre and post Taxotere infusion. Chronic (intermittent) steroids are hurting bone health and have well known immunosuppressive effects. Despite steroid premedication, polysorbate 80-solved Docetaxel (Taxotere) results in occasional infusion reactions due to the solvent polysorbate 80. The new micellar formulation of docetaxel is a promising alternative to polysorbate 80-solved Docetaxel (Taxotere) as it avoids the mandatory need for steroid administration pre and post infusion, and thus avoids immunosuppressive and bone-damaging effects. Safety and pharmacokinetics (PK) of Docetaxel micellar have been assessed in 2 clinical studies, but only in breast cancer patients. This is the first clinical trial to assess the safety and tolerability of 3-weekly intravenous Docetaxel micellar infusions in patients with mCRPC. The primary objective of this study is to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) for Docetaxel micellar in patients with mCRPC.

Conditions

• Metastatic Castration-resistant Prostate Cancer

Interventions

Type	Name	Description
DRUG	Docetaxel micellar	There will be three dose levels, 1-3, with each level consisting initially of a cohort containing 3 patients. One additional dose level, dose level -1, shall be allowed in the event that dose level 1 is considered too toxic

Timeline

• Start date: 2021-05-28
• Primary completion: 2024-01-29
• Completion: 2024-01-29
• First posted: 2020-11-16
• Last updated: 2024-08-01

Locations

3 sites across 1 country: Switzerland