Temsirolimus and Radiation for Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00796796
First received: November 21, 2008
Last updated: July 9, 2013
Last verified: July 2013
  Purpose

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


Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: Temsirolimus
Radiation: Radiation therapy
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Temsirolimus and Thoracic Radiation in Non-Small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Determine the maximum tolerate dose of temsirolimus given with radiation [ Time Frame: 90 days after completion of all patients on treatment ] [ Designated as safety issue: Yes ]
    Treatment lasts approximately 4 weeks


Secondary Outcome Measures:
  • Determine the dose limiting toxicities of temsirolimus and radiation in NSCLC patients [ Time Frame: 90 days after completion of treatment ] [ Designated as safety issue: Yes ]
    Treatment lasts approximately 4 weeks

  • 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 ] [ Designated as safety issue: No ]
  • Safety of the regimen in patients with NSCLC [ Time Frame: 90 days after completion of treatment ] [ Designated as safety issue: Yes ]
    Treatment lasts approximately 4 weeks


Enrollment: 10
Study Start Date: March 2009
Study Completion Date: July 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Torisel
Radiation: Radiation therapy

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00796796

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Maria Q. Baggstrom, M.D. Washington University School of Medicine
  More Information

Additional Information:
Publications:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00796796     History of Changes
Other Study ID Numbers: 08-1259 / 201012882
Study First Received: November 21, 2008
Last Updated: July 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
Non-small cell lung cancer
temsirolimus
radiation therapy

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014