Study of Rapamycin Plus Ketoconazole in Advanced Cancers

NCT ID: NCT00708591

Last Updated: 2014-01-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-10-31
• Study Completion Date: 2008-12-31

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.

Conditions

Advanced Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

Rapamycin

Intervention Type: DRUG

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

Ketoconazole

Intervention Type: DRUG

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.

Interventions

Rapamycin

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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Rapamune; Sirolimus

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Chicago

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ezra Cohen, MD

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Locations

University of Chicago

Chicago, Illinois, United States

Countries

United States

Other Identifiers

13274B

Identifier Type: -

Identifier Source: org_study_id