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Study of Rapamycin Plus Ketoconazole in Advanced Cancers

This study has been completed.
Information provided by (Responsible Party):
University of Chicago Identifier:
First received: June 27, 2008
Last updated: January 16, 2014
Last verified: January 2014
To determine the maximum tolerated dose, observed toxicities, and dose limiting toxicities, and antitumor response of rapamycin plus ketoconazole in patients with advanced cancers.

Condition Intervention Phase
Advanced Cancer Drug: Rapamycin Drug: Ketoconazole Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib Study Administering Rapamycin (Sirolimus) With Ketoconazole in Patients With Advanced Malignancies

Resource links provided by NLM:

Further study details as provided by University of Chicago:

Primary Outcome Measures:
  • maximum tolerated dose [ Time Frame: 4 weeks ]

Secondary Outcome Measures:
  • observed toxicities [ Time Frame: 4 weeks ]
  • anti-tumor response [ Time Frame: 8 weeks ]

Enrollment: 57
Study Start Date: October 2004
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 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.
Other Names:
  • Rapamune
  • Sirolimus
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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts 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.
  Contacts and Locations
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Please refer to this study by its identifier: NCT00708591

United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
Principal Investigator: Ezra Cohen, MD University of Chicago
  More Information

Responsible Party: University of Chicago Identifier: NCT00708591     History of Changes
Other Study ID Numbers: 13274B
Study First Received: June 27, 2008
Last Updated: January 16, 2014

Additional relevant MeSH terms:
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Cytochrome P-450 CYP3A Inhibitors processed this record on September 25, 2017