Temsirolimus and Radiation for Non-Small Cell Lung Cancer

NCT00796796 | Completed Phase 1

• 1 other identifier: 08-1259 / 201012882
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Non-small cell lung cancer; temsirolimus; radiation therapy

Outcome Measures

Primary Outcomes (1)

• Determine the maximum tolerate dose of temsirolimus given with radiation

  Treatment lasts approximately 4 weeks

  90 days after completion of all patients on treatment

Secondary Outcomes (3)

• Determine the dose limiting toxicities of temsirolimus and radiation in NSCLC patients

  90 days after completion of treatment

• Describe phospho-Akt and phospho-S6 levels in circulating mononuclear cells before and after treatment.

  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

  90 days after completion of treatment

Study Arms (2)

Cohort 1 (Starting Dose)

EXPERIMENTAL

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; Radiation: Radiation therapy

Cohort 2

EXPERIMENTAL

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; Radiation: Radiation therapy

Interventions

Temsirolimus DRUG

Also known as: Torisel

Cohort 1 (Starting Dose); Cohort 2

Radiation therapy RADIATION

Cohort 1 (Starting Dose); Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (3)

• Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007 May 31;356(22):2271-81. doi: 10.1056/NEJMoa066838.

  PMID: 17538086 BACKGROUND

• Schmelzle T, Hall MN. TOR, a central controller of cell growth. Cell. 2000 Oct 13;103(2):253-62. doi: 10.1016/s0092-8674(00)00117-3.

  PMID: 11057898 BACKGROUND

• Williams KJ, Telfer BA, Xenaki D, Sheridan MR, Desbaillets I, Peters HJ, Honess D, Harris AL, Dachs GU, van der Kogel A, Stratford IJ. Enhanced response to radiotherapy in tumours deficient in the function of hypoxia-inducible factor-1. Radiother Oncol. 2005 Apr;75(1):89-98. doi: 10.1016/j.radonc.2005.01.009. Epub 2005 Apr 18.

  PMID: 15878106 BACKGROUND

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

temsirolimus; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Maria Q. Baggstrom, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2008
• First Posted: November 24, 2008
• Study Start: March 1, 2009
• Primary Completion: June 1, 2011
• Study Completion: July 1, 2011
• Last Updated: July 11, 2013

Record last verified: 2013-07

Locations

US (1)