Preliminary Study of Mycograb and Docetaxel in Advanced Breast Cancer

Cancer of the Breast Clinical Trial

Official title:

A Phase Ib, Pharmacokinetic, Multiple Center, Open Label Study Evaluating the Safety and Efficacy of Mycograb Administered IV in Combination With Docetaxel in Metastatic or Recurrent Breast Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00217815
• Other study ID #: NTP/ONC/001
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 15, 2005
• Last updated: July 14, 2008
• Start date: September 2005
• Est. completion date: October 2006

Study information

• Verified date: July 2008
• Source: NeuTec Pharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: Poland: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients must be female between the ages of 18 to 70 years old.

2. Patients must have histologically or clinically confirmed metastatic and/or recurrent breast cancer amenable to treatment with docetaxel.

3. Patients must have presence of at least one uni-dimensional measurable lesion with minimal lesion size > 20 mm at the largest diameter.

4. Patients may have had one previous chemotherapy regimen and must not have received prior chemotherapy with docetaxel.

5. Patients must have been off all hormonal therapy for at least 2 weeks prior to initiation of therapy.

6. Patients must have been off all chemotherapy or radiotherapy regimens for at least 4 weeks prior to initiation of chemotherapy.

7. Patients must have a life expectancy of at least 6 months.

8. Patients must have a ECOG status of 0, 1 or 2.

9. Patients must be willing to complete all procedures and visits as outlined in the protocol.

10. Patients must sign an informed consent form.

11. Patients must have negative blood test for HIV and hepatitis B and C.

12. Female patients of child bearing potential should use an effective method of contraception.

Exclusion Criteria:

1. Patients with brain or meningeal metastases.

2. Patients whose only measurable lesion is in the bone.

3. Patients with clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic, respiratory, neurologic, psychiatric, immunologic, gastrointestinal, hematologic, metabolic or any other condition or laboratory abnormality that in the opinion of the investigator makes the patient unsuitable for participation in the study.

4. Patients with history of seizure disorder.

5. Patients who have received treatment with any other investigational drug within the preceding one month.

6. Patients who are pregnant or breast feeding.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Cancer of the Breast

Intervention

Drug:
• Mycograb, Docetaxel

Locations

Country	Name	City	State
Poland	Chemotherapie Clinic of Medical University Lodz	Lodz	Pabianicka
Serbia	Clinical Hospital Centre Bezanijska Kosa	Bezanijska Kosa bb	Belgrade
Serbia	Institute For Oncology and Radiology of Serbia	Pasterova 14	Belgrade

Sponsors (1)

Lead Sponsor	Collaborator
NeuTec Pharma

Countries where clinical trial is conducted

Poland,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Impact on tumour size when compared to historical controls
Secondary	Safety data
Secondary	Pharmacokinetics data