Rapamycin in Advanced Cancers

Advanced Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00707135
• Other study ID #: 13142A
• Status: Completed
• Phase: Phase 1
• First received: June 26, 2008
• Last updated: January 16, 2014
• Start date: June 2005
• 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

The goal of this study is to determine the rapamycin dose equivalent to the recommended phase II/III dose of temsirolimus and determine the observed toxicities and anti-tumor response of rapamycin in patients with advanced cancers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 2008
• Est. primary completion date: September 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 and CLL only) are eligible to participate in the phase Ib portion of the trial only. Patients must have relapsed or refractory disease that is no longer amenable to standard available therapy.

• At least 4 weeks since prior chemotherapy or radiation therapy

• Age >18 years

• ECOG performance status less than or equal to 2

• Life expectancy of greater than 3 months.

• Normal organ and marrow function as defined below:

• No transfusions of packed red blood cells with 1 week of starting treatment. An absolute level of hemoglobin does not constitute an eligibility criterion but patients should be transfused as clinically indicated.

• Leukocytes = 3,000/µL

• WBC = 1,500/µL for patients with hematologic malignancies

• ANC = 1,500/µL (=1,000/µL for patients with hematologic malignancies)

• Absolute lymphocyte count = 1000/µL

• CD4 count = 500/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 upper limit of normal

• 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.

• Ability to understand and the willingness 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. Not recovered from adverse events due to agents administered more than 4 weeks earlier.

• May not be receiving any other investigational agents.

• Uncontrolled brain metastases or malignancy. Patients with brain metastases or a malignant primary brain tumor must have stable neurologic status following local therapy (surgery or radiation) for at least 8 weeks from definitive therapy, and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients cannot be receiving enzyme inducing anti-convulsants.

• 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, history of interstitial lung disease (including pneumonitis, bronchiolitis obliterans with organizing pneumonia, or pulmonary fibrosis) or psychiatric illness/social situations that would limit compliance with study requirements.

• Patients with severe immunodeficient states (as judged by the treating physician.

• Pregnant women, breast-feeding must be stopped

• HIV-positive patients are excluded due to possible pharmacokinetic interactions with rapamycin.

• Concurrent use of ketoconazole, cyclosporine, tacrolimus, and rifampin with rapamycin is not permissible. Concurrent use of rapamycin with diltiazem is allowed but should be done with caution or avoided.

Study Design

Allocation: Non-Randomized, 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
Rapamycin given once weekly in escalating doses. Higher dose levels will be split with the half the dose given on day 1 and half the dose on day 2 (24 hours later).

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
University of Chicago	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose level equivalent to recommended phase 2/3 dose of temsirolimus		6 weeks	No
Primary	observed toxicities		6 weeks	Yes
Primary	anti-tumor effect		6 weeks	No