Defining the Interaction of Docetaxel and Lonafarnib in Patients With Advanced Malignancies
.1.1 Patient must have a pathologically-confirmed locally advanced or
metastatic solid tumor malignancy demonstrated to be refractory to the standard of care,
with tumors accessible by needle or surgical biopsy.
3.1.2 Only patients determined to be at minimal risk to receiving the biopsy (with tumor
location/accessibility as well as underlying patient comorbidities judged to allow a
minimal risk biopsy by the radiologist/surgeon performing the procedure) will be eligible
for this study.
3.1.3 Patient must have an ECOG performance status of 2 or less.
3.1.4 Patient must have a life-expectancy of at least 12 weeks.
3.1.5 Patient must have adequate bone marrow function: WBC ≥ 3,000 cells/mm3, ANC ≥ 1,500
cells/mm3, platelet count ≥ 100,000/mm3 and Hgb ≥ 9.0 g/dL.
3.1.6 Patient must have adequate liver function: total bilirubin level ≤ 2.0 mg/dL and ≤
ULN, albumin ≥ 2.5 g/dL.
3.1.7 Patient must have adequate renal function: Transaminases/Alkaline phosphatase:
AST or ALT and alkaline phosphatase must be within the range allowing for eligibility.
This range is defined as ≤ 2 x ULN.
In determining eligibility, the more abnormal of the two (AST or ALT) should be used.
3.1.8 Patient must have received no more than three previous chemotherapy regimens (prior
chemotherapy may or may not have contained a taxane).
3.1.9 Patient must meet the specified informed consent requirement.
3.1.10 Patient must be of age ≥ 18 years.
3.1.11 Women of childbearing age must have a negative pregnancy test.
3.1.12 Men and women of childbearing potential must be willing to consent to using
effective contraception while on treatment and for at least 3 months thereafter.
3.1.13 Patient must have ≤ Grade 1 neurotoxicity from previous anticancer treatment or
from any cause.
3.1.14 Patient must have adequate coagulation function: INR and PTT ≤ 1.5 x ULN.
3.1.15 Patient must have discontinued all prior chemotherapy and radiotherapy at least 4
weeks prior to registration.
3.1.16 Patient must have discontinued use of the following drugs which are an inducers or
inhibitors of CYP3A4 at least 2 days prior to registration: ethinylestradiol, gestodene,
itraconazole, ketoconazole, cimetidine, erythromycin, carbamazepine, high dose chronic
steroids, phenobarbital, phenytoin, rifampin (rifampcin), and sulfinpyrazone.
Patient must have a pathologically-confirmed
3.2.1 Patient has received more than three previous chemotherapy regimens.
3.2.2 Patient is pregnant or breast feeding.
3.2.3 Patient has signs of symptoms of acute infection requiring systemic therapy.
3.2.4 Patient exhibits confusion, disorientation, or has a history of major psychiatric
illness which may impair the patient's understanding of the informed consent.
3.2.5 Patient's life expectancy is less than 12 weeks.
3.2.6 Patient has > Grade 1 neurotoxicity from previous anticancer treatment or
significant neuropathy from any cause.
3.2.7 Patient requires total parenteral nutrition with lipids.
3.2.8 Inability to swallow the lonafarnib BID.
3.2.9 Patient has a history of uncontrolled heart disease (including clinically
significant coronary artery disease, congestive heart failure and symptomatic or
3.2.10 Patient has a history of severe hypersensitivity reaction to docetaxel or other
drugs formulated with polysorbate 80. Symptoms include: any reaction such as bronchospasm,
generalized urticaria, systolic BP ≤ 80mm Hg, and angioedema.
3.2.11 Use of chronic steroids or anticonvulsants.