Preliminary Study of Mycograb and Docetaxel in Advanced Breast Cancer
Condition: Cancer of the Breast
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The study hypothesis is that the addition of Mycograb to docetaxel will improve outcome in
      advanced carcinoma of the breast.
    

Detailed description: 
      Combination therapies that incorporate new agents have demonstrated the potential to improve
      outcome for patients with metastatic breast carcinoma. Docetaxel has been shown to be a very
      active drug in breast cancer, and anthracycline-based chemotherapy combinations represent the
      most active form of therapy generating objective response rates of between 40-70%. Mycograb®
      was most effective in breast carcinoma cell lines in combination with cisplatin, docetaxel
      and anthracyclines (doxorubicin, daunorubicin).

      We propose that Mycograb® binds to hsp90, inhibiting hsp90 chaperone functioning and
      resulting in the destabilization of key proteins including estrogen/steroid receptors, nitric
      oxide synthase, ras1, MAP (Mitogen-activated protein) kinase, Src, Erb-B2,(erythroblastic
      leukemia viral oncogene homolog 2) HER(human estrogen receptor) kinases and EGFR (epidermal
      grown factor receptor). Over expression of HER2 receptors are observed in malignancies such
      as breast cancer and reportedly have been associated with resistance to chemotherapeutic
      agents. Both maturing and fully mature forms of the receptor depend on hsp90 association for
      stability. Inhibition of hsp90 function down regulates AKT kinase and Src kinase which are
      non-receptor kinase. Therefore, Mycograb® may be of use in estrogen dependent and hormone
      independent breast cancers.

      Mycograb® has been demonstrated to have anti-tumor activity in cell culture. The 50%
      cytotoxicity of Mycograb® on its own is 50 Combination therapies that incorporate new agents
      have demonstrated the potential to improve outcome for patients with metastatic breast
      carcinoma. Docetaxel has been shown to be a very active drug in breast cancer, and
      anthracycline-based chemotherapy combinations represent the most active form of therapy
      generating objective response rates of between 40-70%. Mycograb® was most effective in breast
      carcinoma cell lines in combination with cisplatin, docetaxel and anthracyclines
      (doxorubicin, daunorubicin).

      We propose that Mycograb® binds to hsp90, inhibiting hsp90 chaperone functioning and
      resulting in the destabilization of key proteins including estrogen/steroid receptors, nitric
      oxide synthase, ras1, MAP kinase, Src, Erb-B2, HER kinases and EGFR. Overexpression of HER2
      receptors are observed in malignancies such as breast cancer and reportedly have been
      associated with resistance to chemotherapeutic agents. Both maturing and fully mature forms
      of the receptor depend on hsp90 association for stability. Inhibition of hsp90 function down
      regulates AKT kinase and Src kinase which are non-receptor kinase. Therefore, Mycograb® may
      be of use in estrogen dependent and hormone independent breast cancers.

      Mycograb® has been demonstrated to have anti-tumor activity in cell culture. The 50%
      cytotoxicity of Mycograb® on its own is 50 µg/ml (MCF7 [Breast cancer cell line
      designation]). Mycograb® in combination with docetaxel, doxorubicin and cisplatin and
      Herceptin increased the cytotoxicity in breast cancer cells.

      It is appropriate to evaluate the apparent tumor response and survivor benefits resulting
      from the addition of Mycograb® to a docetaxel containing chemotherapy regimen in metastatic
      or recurrent breast cancer patients.

      (MCF7). Mycograb® in combination with docetaxel, doxorubicin and cisplatin and Herceptin
      increased the cytotoxicity in breast cancer cells.

      It is appropriate to evaluate the apparent tumor response and survivor benefits resulting
      from the addition of Mycograb® to a docetaxel containing chemotherapy regimen in metastatic
      or recurrent breast cancer patients.
    

Intervention name(s): Mycograb, Docetaxel
Intervention type(s): Drug
Intervention MeSH terms: Efungumab; Docetaxel
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment