Clinical trial NCT00708591: Study of Rapamycin Plus Ketoconazole in Advanced Cancers
Official title: A Phase Ib Study Administering Rapamycin (Sirolimus) With Ketoconazole in Patients With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Lead sponsor: University of Chicago
Sponsor class: OTHER
First posted: 2008-07-02
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: maximum tolerated dose
timeFrame: 4 weeks
Secondary outcomes:
measure: observed toxicities
timeFrame: 4 weeks
measure: anti-tumor response
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
Study officials:
affiliation: University of Chicago
name: Ezra Cohen, MD
role: PRINCIPAL_INVESTIGATOR
References: