Official Title: “A Phase Ib Study Administering Rapamycin (Sirolimus) With Ketoconazole in Patients With Advanced Malignancies”

To determine the maximum tolerated dose, observed toxicities, and dose limiting toxicities, and antitumor response of rapamycin plus ketoconazole in patients with advanced cancers.

Study Type: Interventional

Study Design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: September 2008

Intervention(s) in this Clinical Trial

• Drug: Rapamycin
  • Oral Rapamycin once weekly at assigned dose in 4 week cycles. Dosing can continue until disease progression or severe side effects are seen.
• Drug: Ketoconazole
  • 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.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1

Primary Measures

• maximum tolerated dose
  • Time Frame: 4 weeks
    Safety Issue?: Yes

Secondary Measures

• observed toxicities
  • Time Frame: 4 weeks
    Safety Issue?: Yes
• anti-tumor response
  • Time Frame: 8 weeks
    Safety Issue?: 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Chicago

Overall Clinical Trial Officials and Contacts

Ezra Cohen, MD Principal Investigator University of Chicago  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00708591

Study ID Number: UCIRB 13274B

ClinicalTrials.gov Identifier: NCT00708591

Health Authority: United States: Institutional Review Board