Temsirolimus and Radiation for Non-Small Cell Lung Cancer

July 9, 2013 updated by: Washington University School of Medicine

A Phase I Study of Temsirolimus and Thoracic Radiation in Non-Small Cell Lung Cancer (NSCLC)

To determine the maximum tolerated dose of the drug temsirolimus given with radiation therapy for patients with non-small cell lung cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Temsirolimus has demonstrated anti-proliferative and anti-angiogenic activity in multiple epithelial cancers, is well-tolerated, has non-overlapping toxicities with radiation, and has been shown to potentiate the effects of radiation in vitro. Locally advanced non-small cell lung cancer is cured in a minority of patients with concurrent chemoradiation but newer agents are needed. In this study temsirolimus will be studied in combination with radiation in a phase I setting to establish safety.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Patients must have a histologically or cytologically confirmed diagnosis of NSCLC.
  • Patients must have an indication for thoracic radiation.
  • Because all patients will be receiving radiation therapy to a thoracic mass, they must have radiographically measurable disease to participate.
  • Patients may not be candidates for definitive chemoradiation with curative intent.
  • Prior treatment of lung cancer (chemotherapy, radiation therapy, and surgery) are allowed if completed at least 4 weeks prior and if all treatment related toxicities are resolved.
  • At least 18 years of age.
  • Life expectancy of > 12 weeks.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

  • Patients must have adequate organ and marrow function as defined below:

    • leukocytes ≥3,000/mcL
    • absolute neutrophil count ≥1,500/mcL
    • platelets ≥100,000/mcL
    • total bilirubin < 1.5
    • AST(SGOT)/ALT(SGPT) ≤2.5 X institutional upper limit of normal
    • creatinine within normal institutional limits OR
    • creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • The effects of temsirolimus on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing 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. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Patients who have had prior treatment with temsirolimus.
  • Patients may not be receiving any other investigational agents.
  • Patients with symptomatic brain metastases. Known brain metastases are allowed if asymptomatic and previously treated.
  • Patients may not be receiving enzyme-inducing antiepileptic drugs (EIAEDs; e.g., phenytoin, carbamazepine, phenobarbital) nor any other CYP3A4 inducer such as rifampin or St. John's wort, as these may decrease temsirolimus levels. A partial list of agents which interact with cytochrome P450 (CYP3A) is found in Appendix B. Use of agents that potently inhibit CYP3A (and hence may raise temsirolimus levels), such as ketoconazole, is discouraged, but not specifically prohibited. Temsirolimus can inhibit CYP2D6, and may decrease metabolism (and increase drug levels) of drugs that are substrates for CYP2D6, such as codeine. The appropriateness of use of such agents is left to physician discretion. A list of drugs that may have potential interactions with CYP2D6 is found in Appendix B. If there is any doubt about eligibility based on concomitant medication, the Principal Investigator should be contacted. All concomitant medications must be recorded.
  • Patients with known hypersensitivity reactions to macrolide antibiotics (such as erythromycin, clarithromycin, and azithromycin).
  • 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.
  • Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
  • Patients having received prior thoracic radiation therapy directed to the tumor volume to be treated with radiotherapy on this protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1 (Starting Dose)

Temsirolimus 20 mg IV weekly for 4 weeks

Radiation therapy will begin on Day 2, one day after the initial dose of temsirolimus. Treatment will consist of daily fractions of 250 cGy, 5 days per week to a total cumulative dose of 3500 cGy for a total of 14 days.
Drug: Temsirolimus
Other Names:
  • Torisel
Radiation: Radiation therapy
Experimental: Cohort 2

Temsirolimus 25 mg IV weekly for 4 weeks

Radiation therapy will begin on Day 2, one day after the initial dose of temsirolimus. Treatment will consist of daily fractions of 250 cGy, 5 days per week to a total cumulative dose of 3500 cGy for a total of 14 days.
Drug: Temsirolimus
Other Names:
  • Torisel
Radiation: Radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the maximum tolerate dose of temsirolimus given with radiation
Time Frame: 90 days after completion of all patients on treatment
Treatment lasts approximately 4 weeks
90 days after completion of all patients on treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the dose limiting toxicities of temsirolimus and radiation in NSCLC patients
Time Frame: 90 days after completion of treatment
Treatment lasts approximately 4 weeks
90 days after completion of treatment
Describe phospho-Akt and phospho-S6 levels in circulating mononuclear cells before and after treatment.
Time Frame: Prior to initial temsirolimus dose, one hour post completion of initial temsirolimus dose, and prior to second temsirolimus dose
Prior to initial temsirolimus dose, one hour post completion of initial temsirolimus dose, and prior to second temsirolimus dose
Safety of the regimen in patients with NSCLC
Time Frame: 90 days after completion of treatment
Treatment lasts approximately 4 weeks
90 days after completion of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2009

Primary Completion (Actual)

June 1, 2011

Study Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

November 21, 2008

First Submitted That Met QC Criteria

November 21, 2008

First Posted (Estimate)

November 24, 2008

Study Record Updates

Last Update Posted (Estimate)

July 11, 2013

Last Update Submitted That Met QC Criteria

July 9, 2013

Last Verified

July 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-1259 / 201012882

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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