Study of Rapamycin Plus Ketoconazole in Advanced Cancers

NCT00708591 | Completed Phase 1 DMC

• 1 other identifier: 13274B
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• maximum tolerated dose

  4 weeks

Secondary Outcomes (2)

• observed toxicities

  4 weeks

• anti-tumor response

  8 weeks

Study Arms (1)

1

EXPERIMENTAL

Drug: Rapamycin; Drug: Ketoconazole

Interventions

Rapamycin DRUG

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

Also known as: Rapamune, Sirolimus

1

Ketoconazole 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.

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Interventions

Sirolimus; Ketoconazole

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ezra Cohen, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2008
• First Posted: July 2, 2008
• Study Start: October 1, 2004
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: January 17, 2014

Record last verified: 2014-01

Locations

US (1)