Study of Rapamycin Plus Ketoconazole in Advanced Cancers

Phase 1

Completed

• Conditions: Advanced Cancer
• Interventions: Drug: Rapamycin; Drug: Ketoconazole

• Registration Number: NCT00708591
• Lead Sponsor: University of Chicago

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2004-10
• Study First Submitted: 2008-06-27
• Study First Submitted QC: 2008-07-01
• Study First Posted: 2008-07-02
• Primary Completion: 2008-12
• Study Completion: 2008-12
• Status Verified: 2014-01
• Last Update Submitted: 2014-01-16
• Last Update Posted: 2014-01-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 57

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	Ketoconazole	-
1	Rapamycin	-

Primary Outcome Measures

Name	Time	Method
maximum tolerated dose	4 weeks

Secondary Outcome Measures

Name	Time	Method
observed toxicities	4 weeks
anti-tumor response	8 weeks

Trial Locations

Locations (1)

University of Chicago; 🇺🇸 Chicago, Illinois, United States