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

NCT00769600 | Terminated Phase 2 Results DMC

• 2 other identifiers: J0881JSNA_00020074
• Study Type: interventional
• Target: 23
• Locations: 2 countries
• Sites: 2

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.

Conditions

Recurrent Non Small Cell Lung Cancer

Keywords

Recurrent Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Overall Survival

  Median number of days alive

  up to 3 years

• Progression Free Survival as Measured by Number of Days Without Disease Progression

  1 year

• RECIST Response

  Number of participants with partial response (PR), stable disease (SD) and progressive disease (PD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST)

  Up to 3 years

Secondary Outcomes (2)

• Tumor Blood Flow

  3 years

• Tumor Metabolic Activity

  3 years

Study Arms (2)

Itraconazole with Pemetrexed

ACTIVE COMPARATOR

Pemetrexed IV every 21 days with oral Itraconazole 200mg daily.

Drug: Itraconazole; Drug: Pemetrexed

Single agent pemetrexed

ACTIVE COMPARATOR

Pemetrexed IV on day 1 of 21-day cycle.

Drug: Pemetrexed

Interventions

Itraconazole DRUG

Itraconazole 200 mg once daily

Also known as: Sporanox

Itraconazole with Pemetrexed

Pemetrexed DRUG

Pemetrexed every 21 days.

Also known as: Alimta

Itraconazole with Pemetrexed; Single agent pemetrexed

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (2)

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Singapore General Hospital

Tiong Bahru Estate, 308433, Singapore

Location

Related Publications (1)

• Rudin CM, Brahmer JR, Juergens RA, Hann CL, Ettinger DS, Sebree R, Smith R, Aftab BT, Huang P, Liu JO. Phase 2 study of pemetrexed and itraconazole as second-line therapy for metastatic nonsquamous non-small-cell lung cancer. J Thorac Oncol. 2013 May;8(5):619-23. doi: 10.1097/JTO.0b013e31828c3950.

  PMID: 23546045 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Itraconazole; Pemetrexed

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)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: Charles Rudin, MD
• Organization: MSKCCC

rudinc@mskcc.edu

646-888-4336

Study Officials

• Charles M Rudin, MD, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2008
• First Posted: October 9, 2008
• Study Start: November 1, 2008
• Primary Completion: January 1, 2013
• Study Completion: February 1, 2013
• Last Updated: February 1, 2019
• Results First Posted: February 1, 2019

Record last verified: 2019-01

Locations

SG (1); US (1)