Study of Rapamycin Plus Ketoconazole in Advanced Cancers

Advanced Cancer Clinical Trial

Official title:

A Phase Ib Study Administering Rapamycin (Sirolimus) With Ketoconazole in Patients With Advanced Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00708591
• Other study ID #: 13274B
• Status: Completed
• Phase: Phase 1
• First received: June 27, 2008
• Last updated: January 16, 2014
• Start date: October 2004
• Est. completion date: December 2008

Study information

• Verified date: January 2014
• Source: University of Chicago
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Cancer
• Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	maximum tolerated dose		4 weeks	Yes
Secondary	observed toxicities		4 weeks	Yes
Secondary	anti-tumor response		8 weeks	No