Rapamycin in Advanced Cancers

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: Rapamycin

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	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).; Other Names: Rapamune; sirolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose level equivalent to recommended phase 2/3 dose of temsirolimus	6 weeks
observed toxicities	6 weeks
anti-tumor effect	6 weeks

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: June 26, 2008
• First Submitted That Met QC Criteria: June 26, 2008
• First Posted (Estimate): June 30, 2008

Study Record Updates

• Last Update Posted (Estimate): January 17, 2014
• Last Update Submitted That Met QC Criteria: January 16, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: 13142A