Official Title: “A Study of the Proper Dosage of Lovastatin and Docetaxel for Patients With Cancer”

This purpose of this study is to evaluate the use of two medications, docetaxel and lovastatin. There are two phases. Subjects in Phase I can have any cancer. This phase will determine the highest dose of lovastatin and docetaxel that can be given safely as well as the safety of combining the two drugs and the effect on the subject's tumor. Phase II will administer lovastatin and docetaxel only to subjects who have breast cancer tumors.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: April 2009

The primary objective of this study is to determine the maximum tolerated dose (MTD) of lovastatin and docetaxel in patients with various different cancers (phase I). Once the MTD for this drug combination has been determined, patients with breast cancer will be entered into a single cohort, the phase II portion of this study, and treated with the MTD doses of both lovastatin and docetaxel.

Intervention(s) in this Clinical Trial

• Drug: Lovastatin and Docetaxel
  • Docetaxel (60 mg/m2) will be given on day 0 every three weeks in Phase I with incrementally increasing doses of lovastatin. Lovastatin will be administered p.o. following a four times a day schedule, for four consecutive days (days -1 to +2) and repeated every three weeks. For purposes of this phase I/II study, intermittent drug administration, six dose levels, ranging from 2 to 24 mg/kg/day (2, 4, 7, 10, 13, 18, and 24 mg) will be used. Once the maximum tolerated dose (MTD) of lovastatin has been determined, docetaxel will be escalated in a stepwise scheme from 60 to 80 to 100 mg/m2.

Primary Measures

• For the Phase II portion of the study, the primary endpoint is frequency of objective response (complete response or partial response).
  • Time Frame: 12 weeks
    Safety Issue?: No

Inclusion Criteria:

• Age > 18 years of age
• Performance Status (ECOG) <2
• Peripheral Neuropathy < grade I
• Signed Informed consent
• Hematologic-Inclusion Absolute neutrophil count > 1,500/mm3 Hemoglobin > 8.0 g/dl
• Platelet count > 100,000/mm3.
• Hepatic-Inclusion Total Bilirubin must be within normal limits.
• Transaminases (SGOT and/or SGPT) may be up to 2.5 x institutional upper limit of normal (ULN) if alkaline phosphatase is < ULN, or alkaline phosphatase may be up to 4 x ULN if transaminases are < ULN.
• Patients may have received prior chemotherapy including treatment with the following agents: anthracycline, platinum, vinorelbine, or other Vinca alkaloids. The patient must have recovered from the side effects of the prior treatment including prior drug-induced peripheral neuropathy.
• Patients who have received prior taxane therapy will be eligible. (However, patients who have progressed within 6 months of receiving docetaxel will be excluded.)
• A minimum of 28 days must have elapsed from the completion of any prior chemotherapy or radiation treatment.
• Patients who are currently receiving bisphosphonates for bone disease will be allowed to enter the trial, however their bone lesions will not be considered assessable for response, but will be assessable for progression.
• Initiation of bisphosphonate treatment during the trial will be discouraged but allowed in the absence of progressive disease. If bisphosphonates are initiated, then bone lesions will be assessed for progression only.

Exclusion Criteria:

• Other serious illnesses, which would limit survival to <2 months, or a psychiatric condition, which would prevent compliance with treatment or informed consent.
• ECOG Performance Status >2
• Anticipated survival < 2 months
• Uncontrolled or severe cardiovascular disease, diabetes, pulmonary disease, or infection, which in the opinion of the treating physician would make this protocol treatment unreasonably hazardous for the patient.
• Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and considered by their physician to be at less than 30% risk of relapse within one year.
• Patients who have received any investigational agent within the prior 4 weeks.
• Age < 18 as there is no safety data for lovastatin in this age range.
• Patients with a history of severe hypersensitivity reaction to Taxotere® or other drugs formulated with polysorbate 80.
• Patients who have received anticancer endocrine therapy within 4 weeks prior to registration are not eligible.
• Patients currently on daily statin therapy will also be excluded.
• Patients who have progressed within 6 months of receiving docetaxel are not eligible.
• Treatment with the anti-emetic Aprepitant is not allowed.
• Patients who are currently receiving , or have received Herceptin therapy within 4 weeks prior to registration are not eligible.
• Pregnant and/or Nursing. Patients must not be pregnant or nursing at the time of enrollment nor while under the treatment of this protocol.
• Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective means of birth control.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 19 Years

Maximum Age for this Clinical Trial: 90 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Iowa

Overall Clinical Trial Officials and Contacts

Susan Roman, DO Principal Investigator University of Iowa  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00584012

Study ID Number: 200311038

ClinicalTrials.gov Identifier: NCT00584012

Health Authority: United States: Food and Drug Administration