Advanced Cancer
Conditions
Brief summary
To determine the maximum tolerated dose, observed toxicities, and dose limiting toxicities, and antitumor response of rapamycin plus ketoconazole in patients with advanced cancers.
Interventions
DRUGRapamycin
Oral Rapamycin once weekly at assigned dose in 4 week cycles. Dosing can continue until disease progression or severe side effects are seen.
DRUGKetoconazole
Twice daily (200mg each time) at the start of the second week of therapy for 4 consecutive days. Dosing continues every week after the second week of therapy.
Sponsors
University of Chicago
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. * Patients with hematologic malignancies (lymphoma, multiple myeloma and CLL only) are eligible to participate in the phase Ib portion of the trial only * At least 4 weeks since prior chemotherapy or radiation therapy (6 weeks if the last regimen included BCNU or mitomycin C). * Age \>18 years. * ECOG performance status less than or equal to 2 * Life expectancy of more than 3 months. * Normal organ and marrow function as defined below: * Hemoglobin ≥ 10 g/dl * Leukocytes ≥ 3,000/µL o WBC ≥ 1,500/µL for patients with hematologic malignancies * Absolute neutrophil count ≥ 1,500/µL (≥ 1,000/µL for patients with hematologic malignancies) * Absolute lymphocyte count ≥1000/µL * Platelets ≥ 100,000/µL (≥ 50,000/µL for patients with hematologic malignancies) * Total bilirubin within normal institutional limits * AST (SGOT) and ALT (SGPT) ≤ 2.5 times institutional ULN * Serum triglycerides ≤ 500 mg/dl * Creatinine within normal institutional limits OR * Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. * Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. * Able to understand and the willing to sign a written informed consent document.
Exclusion criteria
* Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or not recovered from adverse events due to agents administered more than 4 weeks earlier. * Receiving any other investigational agents. * Uncontrolled brain metastases or malignancy. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to rapamycin. * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Severe immunodeficient state (as judged by the treating physician) * Pregnancy (breast-feeding must be discontinued) * HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with rapamycin. * Concurrent use of cyclosporine, tacrolimus, and rifampin, terfenadine, astemizole, cisapride, rosiglitazone or pioglitazone due to possible interactions with the study drugs. Ketoconazole cannot be taken within 2 hours of an antacid.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| maximum tolerated dose | 4 weeks |
Secondary
| Measure | Time frame |
|---|---|
| observed toxicities | 4 weeks |
| anti-tumor response | 8 weeks |
Countries
United States
Outcome results
None listed