Clinical trial NCT00068757 (phase 1, status: completed)
Conditions: breast cancer
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: lonafarnib, paclitaxel
SMILES: NC(=O)N1CCC(CC(=O)N2CCC(CC2)[C@H]2C3=C(CCC4=C2C(Br)=CC(Cl)=C4)C=C(Br)C=N3)CC1, [H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](OCCO)[C@@H](C1)OC
Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically or cytologically confirmed breast cancer

               -  Stage IIIB, IIIC, or IV

          -  HER2/neu overexpression

               -  3+ by immunohistochemistry

                    -  2+ allowed if positive fluorescent in situ hybridization

          -  Disease meets the following treatment criteria:

               -  Paclitaxel/trastuzumab (Herceptin®) may be appropriate therapy

               -  Anthracycline therapy is not a suitable approach

          -  No clinical signs of CNS involvement

          -  Hormone receptor status:

               -  Not specified

        PATIENT CHARACTERISTICS:

        Age

          -  18 and over

        Sex

          -  Male or female

        Menopausal status

          -  Not specified

        Performance status

          -  ECOG 0-2 OR

          -  WHO 0-2

        Life expectancy

          -  Not specified

        Hematopoietic

          -  Neutrophil count at least 1,500/mm^3

          -  Platelet count at least 100,000/mm^3

          -  Hemoglobin at least 10.0 g/dL (6.2 mmol/L)

        Hepatic

          -  Bilirubin no greater than 1.5 times upper limit of normal (ULN)

          -  Alkaline phosphatase less than 2.5 times ULN (5 times ULN if liver metastases are
             present)

          -  AST and ALT less than 2.5 times ULN (5 times ULN if liver metastases are present)

        Renal

          -  Creatinine clearance at least 40 mL/min

        Cardiovascular

          -  Cardiac ejection fraction normal by MUGA

          -  QTc interval no greater than 440 msec

          -  No cardiac dysfunction

        Other

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for up to 3 months after
             study participation

          -  No concurrent severe/unstable systemic disease

          -  No infection

          -  No circumstances that would preclude study participation (e.g., alcoholism or
             substance abuse)

          -  No psychological, familial, sociological, or geographical condition that would
             preclude study compliance and follow-up

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  More than 1 year since prior trastuzumab

          -  No concurrent prophylactic growth factors

        Chemotherapy

          -  More than 1 year since prior paclitaxel

          -  More than 4 weeks since other prior chemotherapy

        Endocrine therapy

          -  More than 1 day since prior hormonal therapy

          -  More than 2 days since prior high-dose chronic steroids

          -  More than 2 days since prior ethinyl estradiol

          -  No concurrent high-dose chronic steroids

          -  No concurrent ethinyl estradiol

        Radiotherapy

          -  More than 4 weeks since prior radiotherapy

        Surgery

          -  Not specified

        Other

          -  More than 2 days since prior administration of and no concurrent CYP3A4 inducers or
             inhibitors, including any of the following:

               -  Gestodene

               -  Itraconazole

               -  Ketoconazole

               -  Cimetidine

               -  Erythromycin

               -  Carbamazepine

               -  Phenobarbital

               -  Phenytoin

               -  Rifampin

               -  Sulfinpyrazone

          -  No concurrent grapefruit juice

          -  No other concurrent anticancer agents

          -  No other concurrent investigational therapy