Rapamycin in Advanced Cancers

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Chicago
ClinicalTrials.gov Identifier:
NCT00707135
First received: June 26, 2008
Last updated: January 16, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Advanced Cancer
Drug: Rapamycin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib Study of Rapamycin (Sirolimus) in Patients With Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by University of Chicago:

Primary Outcome Measures:
  • Dose level equivalent to recommended phase 2/3 dose of temsirolimus [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • observed toxicities [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • anti-tumor effect [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: June 2005
Study Completion Date: December 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00707135

Locations
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
  More Information

No publications provided

Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT00707135     History of Changes
Other Study ID Numbers: 13142A
Study First Received: June 26, 2008
Last Updated: January 16, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Neoplasms
Sirolimus
Everolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 20, 2014