Indibulin (Zybulin), an oral pill to treat metastatic breast cancer developed by Ziopharm Oncology, Inc. is currently undergoing first in man studies.
Ziopharm Oncology has initiated a Phase I/II study of oral indibulin (Zybulin) at Memorial Sloan-Kettering Cancer Center.
The phase I trial is expected to enroll approximately 20 patients and will determine the maximum tolerated dose of oral indibulin implementing the “mathematically modeled” dose administration schedule.
This 5 days on and 9 days off model that capitalizes on the convenience of oral administration, also maximizes drug activity and limit potential toxicity and resistance, Ziopharm Oncology said in a press release.
Indibulin is a novel, oral tubulin binding agent that targets both mitosis and cancer cell migration.
Indibulin is expected to have several potential benefits, including oral dosing, application in multi-drug resistant tumors, no neuropathy, and minimal overall toxicity.
In initial studies oral indibulin has been administered both as a single agent and in combination with favorable activity, and has a promising safety profile that does not include the neurotoxicity seen with all of the other classes of tubulin binding agents. The trial will be continued into Phase II once dose has been established in Phase I.
“The development of an additional new therapy for breast cancer that is effective but with fewer of the more significant side effects associated with many commonly used therapies would be an important step in the treatment of this disease,” stated Clifford A. Hudis, M.D., Chief of the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center.
The study will implement a mathematically modeled drug administration schedule that was developed in preclinical studies by Larry Norton, M.D. as a consultant to Ziopharm Oncology, Inc.
The model capitalizes on the convenience and scheduling flexibility of oral administration to maximize anticancer activity, minimize potential toxicity and resistance, and exploit the drug’s mechanisms of action on both cancer cell division and cell movement. Findings from the preclinical studies were presented at the 2009 American Society of Clinical Oncology annual meeting.
Memorial Sloan-Kettering’s Breast Cancer Medicine team has successfully translated preclinical work into meaningful clinical treatment in past studies, and will lead this Phase I/II trial.
Ziopharm Oncology is a biopharmaceutical company engaged in the development and commercialization of a diverse portfolio of cancer drugs. The Company is currently focused on three clinical programs.
Palifosfamide (Zymafos or ZIO-201) references a novel composition (tris formulation) that comprises the functional active metabolite of ifosfamide, a standard of care for treating sarcoma, lymphoma, testicular, and other cancers.
Palifosfamide delivers only the cancer fighting component of ifosfamide. It is expected to overcome the resistance seen with ifosfamide and cyclophosphamide, two of the most commonly used DNA-alkylating drugs used to treat cancers.
Palifosfamide does not have the toxic metabolites of ifosfamide that cause the debilitating side effects of “fuzzy brain” (encephalopathy) and severe bladder inflammation.
Intravenous palifosfamide is currently in a randomized Phase II trial to treat unresectable or metastatic soft tissue sarcoma in the front- and second-line setting with the company having reported interim positive results in late 2009; a registration trial in the same setting is expected to initiate following U.S. Food and Drug Administration review in the first half of this year. An oral form of palifosfamide has been developed preclinically to the investigational new drug application stage.
Darinaparsin (Zinapar or ZIO-101) is a novel mitochondrial-targeted agent (organic arsenic) being developed for the treatment of various hematologic and solid cancers.
Preclinical and clinical studies to date have demonstrated that darinaparsin is considerably less toxic than inorganic arsenic, particularly with regard to cardiac toxicity.
The company has reported results from a phase II trial with IV-administered darinaparsin in lymphoma, particularly peripheral T-cell lymphoma, at the American Society of Clinical Oncology (ASCO) in May of 2009 which would serve as the basis for ongoing clinical study in PTCL following regulatory review and available financial resources. Phase I trials with an oral form are ongoing in both hematological malignancies and solid tumors.