Table 2.
Clinical trials describing brain penetrance and nervous system side effects for microtubule stabilizing agents.
| Name(s) | Cytoskeletal target | Diseases | Clinicaltrials.gov identifier (Status- study completion date) | BBB penetrance/side effects |
|---|---|---|---|---|
| Epothilone D (KOS-862, NSC-703147, desoxyepothilone B BMS-241027) | Tubulin | Alzheimer's Disease | NCT01492374 (C) (October 2013) | Brain penetrant/Neurotoxicity severe diarrhea |
| Lung cancer | NCT00080509 (T) (November 2004) NCT00081107(C) (December 2004) | |||
| Colorectal cancer | NCT00077259 (C) (September 2004) | |||
| Breast cancer | NCT00337649 (C) (April 2008) | |||
| Prostate cancer | NCT00104130 (T) (February 2005) | |||
| BMS-247550 (ixabepilone) | Tubulin | Breast Cancer | NCT00082433 (C) (March 2008) NCT00789581 (C) (October 2013) | Brain penetrant/CIN, neutropenia, nausea, fatigue, arthralgia, alopecia |
| BMS-310705 | Tubulin | Solid tumors | Phase I (Sessa et al., 2007) (C) | Brain penetrant/neurotoxicity, severe diarrhea |
| NAP (AL-108, AL-208, davunetide NAPVSIPQ) | EB1/EB3 | Schizophrenia | NCT00505765 (C) (April 2009) | Brain penetrant/One patient reported palpitations |
| Taupathies | NCT01056965 (A) (July 2017) | |||
| Mild cognitive impairment in Alzheimer's disease | NCT00422981 (C) (January 2008) NCT00404014 (C) (June 2008) | |||
| PSP | NCT01110720 (C) (December 2012) NCT01049399 (C) (November 2011) | |||
| TPI 287 (ARC-100) | Unknown | Alzheimer's Disease | NCT01966666 (A) (Est. completion: March 2019) | Brain penetrant/ Seizures, Grade III CIN |
| Corticobasal Syndrome, PSP | NCT02133846 (A) (Est. completion: March 2019) | |||
| Neuroblastoma | NCT00867568 (C) (February 2016) NCT01483820 (T) (December 2014) | |||
| Metastatic melanoma | NCT01067066 (T) (July, 2016) | |||
| Paclitaxel | Taxol-binding domain | Approved for ovarian, breast and non-small cell lung carcinomas, AIDS-related Kaposi's Sarcoma | Numerous clinical trials | Non-brain penetrant/CIN, neutropenia |
| ANG1005 (GRN1005) | Taxol-binding domain | Brain metastasis | NCT01497665 (T) (February 2013) NCT02048059 (C) (September 2017) NCT01967810 (C) (September 2017) NCT01480583 (C) (October 2015) | Brain penetrant/neutropenia |
| Sagopilone (ZK-EPO, ZK 219477) | Tubulin | Brain metastasis | NCT00496379 (T) (January 2012 | Brain penetrant/fatigue, CIN, nausea,diarrhea, leucopenia hepatobiliary disorder |
| Recurrent Glioblastoma | NCT00424060 (C) (August 2007) | |||
| Metastatic melanoma | NCT00598507 (C) (January 2013) | |||
| Triazolopyrimidines, Cevipabulin | Vinca site | Advanced malignant solid tumors | NCT00195247 (T) (Not mentioned) NCT00195325 (T) (Not mentioned) | Non brain penetrant/Not reported |
| IDN-5109 (BAY 59-8862, Ortataxel) | Tubulin | Recurrent glioblastoma | NCT01989884 (S) (December 2016 | Brain penetrant/Not reported |
| Taxane-refractory NSCLC | NCT00054314 (C)(April 2003) NCT00044538 (C) (June 2004) | |||
| Metastatic breast cancer | NCT00044525 (C) (February 2004) | |||
| Refractory Non-Hodgkin's Lymphoma | NCT00044551 (C) (July 2003) | |||
| Renal cell carcinoma | NCT00044564 (C) (January 2003) | |||
| Cabazitaxel (Jevtana, XRP-6258) | Tubulin | Prostate cancer | NCT00417079 (C) (September 2009) | Brain penetrant/ hypotension, bronchospasm, generalized rash/erythema, severe diarrhea, neutropenia, neurotoxicity fatigue, alopecia, Grade 1 neurotoxicity |
| Head and neck cancer | NCT01620242 (C) (April 2015) | |||
| Breast cancer | NCT01934894 (T) (April 2017) NCT03048942 (A) (Est. completion: August 2022) | |||
| NSCLC | NCT01438307 (C) (September 2015) NCT01852578 (C) (August 2013) | |||
| Refractory Glioblastoma Multiforme | NCT01866449 (C) (August 2017) |