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Phase II Study of Itraconazole and Pemetrexed in Patients With Previously Treated Non-Squamous NSCLC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00769600
Recruitment Status : Terminated (Low accrual.)
First Posted : October 9, 2008
Results First Posted : February 1, 2019
Last Update Posted : February 1, 2019
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:

Primary Objective

To evaluate the 3-month event-free survival of the combination of the combination of itraconazole and pemetrexed in patients with recurrent/refractory non-small cell lung cancer.

Secondary Objectives

To determine the objective response rate of the combination of itraconazole and pemetrexed in patients with recurrent/refractory non-small cell lung cancer.


Condition or disease Intervention/treatment Phase
Recurrent Non Small Cell Lung Cancer Drug: Itraconazole Drug: Pemetrexed Phase 2

Detailed Description:

Primary Objective

To evaluate the 3-month event-free survival of the combination of the combination of itraconazole and pemetrexed in patients with recurrent/refractory non-small cell lung cancer. 3-month event-free survival (EFS) is defined as the proportion of patients who are alive and without event after 3 months (evaluated in a window of +/- 1 week) of treatment. Events are defined as disease progression or death from any cause. All patients treated on protocol will be included in the determination of EFS, regardless of treatment modification or discontinuation.

Secondary Objectives

To determine the objective response rate of the combination of itraconazole and pemetrexed in patients with recurrent/refractory non-small cell lung cancer. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Itraconazole and Pemetrexed in Patients With Previously Treated Non-Squamous Non-Small Cell Lung Cancer
Study Start Date : November 2008
Actual Primary Completion Date : January 2013
Actual Study Completion Date : February 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Active Comparator: Itraconazole with Pemetrexed
Pemetrexed IV every 21 days with oral Itraconazole 200mg daily.
Drug: Itraconazole
Itraconazole 200 mg once daily
Other Name: Sporanox

Drug: Pemetrexed
Pemetrexed every 21 days.
Other Name: Alimta

Active Comparator: Single agent pemetrexed
Pemetrexed IV on day 1 of 21-day cycle.
Drug: Pemetrexed
Pemetrexed every 21 days.
Other Name: Alimta




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: up to 3 years ]
    Median number of days alive

  2. Progression Free Survival as Measured by Number of Days Without Disease Progression [ Time Frame: 1 year ]
  3. RECIST Response [ Time Frame: Up to 3 years ]
    Number of participants with partial response (PR), stable disease (SD) and progressive disease (PD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST)


Secondary Outcome Measures :
  1. Tumor Blood Flow [ Time Frame: 3 years ]
    Tumor blood flow activity in patients with previously treated non-squamous non-small cell lung cancer receiving pemetrexed alone or pemetrexed plus itraconazole.

  2. Tumor Metabolic Activity [ Time Frame: 3 years ]
    Tumor metabolic activity in patients with previously treated non-squamous non-small cell lung cancer receiving pemetrexed alone or pemetrexed plus itraconazole.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed NSCLC.
  • Patient must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See Section 11 for the evaluation of measurable and non-measurable disease.
  • Patients must have received at least one previous chemotherapy regimen and have recurrent or refractory disease.
  • Age >18 years. Because no dosing or adverse event data are currently available on the use of itraconazole in combination with pemetrexed in patients < 18 years of age, such patients are excluded from this study but will be eligible for future pediatric phase 2 combination trials.
  • Life expectancy of greater than 12 weeks.
  • ECOG performance status < 2 (Karnofsky > 60%; see Appendix A).
  • Patients must have normal organ and marrow function as defined below:

    • leukocyte > 3,000/mcL
    • absolute neutrophil count > 1,500/mcL
    • platelets > 100,000/mcL
    • total bilirubin within normal institutional limits
    • AST(SGOT)/ALT(SGPT)< 2.5 X institutional upper limit of normal
    • creatinine within normal institutional limits
    • creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • 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 chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
  • Patients may not be receiving any other investigational agents.
  • Patients who have received prior pemetrexed chemotherapy.
  • Patients with uncontrolled brain metastases. Patients with brain metastases must have stable neurologic status following local therapy (surgery or radiation) for at least 2 weeks, and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to itraconazole and pemetrexed or other agents used in the study.
  • Itraconazole is a strong CYP3A4 inhibitor and may increase plasma concentrations of drugs metabolized by this pathway. Coadministration of cisapride, midazolam, pimozide, quinidine, lovastatin, simvastatin, triazolam, dofetilide, or levacetylmethadol (levomethadyl) with itraconazole is contraindicated. Patients who take any of these medications and who are not able to change to an alternative medication will be excluded. Lists including medications and substances known or with the potential to interact with the CYP3A4 isoenzymes are provided in Section 7.1.
  • 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.
  • Pregnant women are excluded from this study because itraconazole and pemetrexed are Class C and D agents, respectively, with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with itraconazole and pemetrexed, breastfeeding should be discontinued if the mother is treated with itraconazole or pemetrexed. These potential risks may also apply to other agents used in this study.
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with itraconazole or pemetrexed. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00769600


Locations
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United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21231
Singapore
Singapore General Hospital
Tiong Bahru Estate, Singapore, 308433
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Investigators
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Principal Investigator: Charles M Rudin, MD, PhD Johns Hopkins University

Publications of Results:
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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00769600     History of Changes
Other Study ID Numbers: J0881JS
NA_00020074 ( Other Identifier: Johns Hopkins Institutional Review Board 2 )
First Posted: October 9, 2008    Key Record Dates
Results First Posted: February 1, 2019
Last Update Posted: February 1, 2019
Last Verified: January 2019
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Recurrent Non-Small Cell Lung Cancer
Additional relevant MeSH terms:
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Itraconazole
Hydroxyitraconazole
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pemetrexed
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors