A Phase 2 study of ALIMTA in solid tumor patients with stable third-space fluid

• Register: EUCTR
• Last refreshed on: 5 November 2012
• Main ID: EUCTR2005-005535-10-DK
• Date of registration: 13/03/2007
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company Limited
• Public title: A Phase 2 study of ALIMTA in solid tumor patients with stable third-space fluid
• Scientific title: A Phase 2 study of ALIMTA in solid tumor patients with stable third-space fluid
• Date of first enrolment: 13/04/2007
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-005535-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Denmark, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
Patients are eligible to be included in this study only if they meet all of the following criteria:
[1] Histologic or cytologic diagnosis of locally advanced or metastatic (Stage III or IV at entry) NSCLC that is not amenable to curative therapy or histologic diagnosis of mesothelioma of the pleura or peritoneum that is not amenable to curative therapy.
Patients with NSCLC must have been previously treated with one platinum-containing chemotherapy regimen for locally advanced or metastatic disease.
Patients with malignant pleural or peritoneal mesothelioma may have received one previous chemotherapy regimen and, at the discretion of the investigator, be clinical candidates for treatment with single-agent pemetrexed.
[2] Presence of clinically detectable (by physical exam) and stable-appearing third-space fluid (ascites or pleural effusions).
[3] Measurable lesions are not required for enrollment in this study.
[4] Prior anticancer treatment (except radiation) must be completed at least 3 weeks prior to study enrollment, and the patient must have recovered from the acute toxic effects of the regimen.
[5] Prior radiation therapy is allowed to <25% of the bone marrow. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed at least 2 weeks before study enrollment, and the patient must have recovered from the acute toxic effects of the treatment prior to study enrollment.
[6] An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. (Oken et al. 1982; see Protocol Attachment JMHX.3.)
[7] Estimated life expectancy of at least 8 weeks.
[8] Patient compliance and geographic proximity that allow adequate follow-up.
[9] Adequate organ function that includes the following indices:
Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ?1.5 ? 109/L, platelets ?100 ? 109/L, and hemoglobin ?9 g/dL.

Hepatic: bilirubin ?1.5 ? the upper limit of normal (ULN), alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT) ?3.0 ? ULN (ALP, AST, and ALT ?5 ? ULN is acceptable if the liver has tumor involvement).

Renal: calculated CrCl >45 mL/min using the original, weight-based Cockcroft and Gault formula (Cockcroft and Gault 1976; see Protocol Attachment JMHX.4). Creatinine clearance enrollment and dosing decisions will be based on local laboratory values. A patient will be enrolled using the local laboratory value. The same local laboratory should be used throughout the study for dosing decisions.

[10] Signed informed consent from patient.
[11] Males or females at least 18 years of age.
[12] Male and female patients with reproductive potential must use an approved contraceptive method if appropriate (for example, intrauterine device, birth control pills, or barrier device) during, and for 6 months after, treatment. Females with childbearing potential must have a negative serum pregnancy test within 7 days before study enrollment.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients will be excluded from the study if they meet any of the following criteria:
[13] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
[14] Active infection that, in the opinion of the investigator, would compromise the patient’s ability to tolerate therapy.
[15] Pregnant.
[16] Breast-feeding.
[17] Serious concomitant systemic disorders that would compromise the safety of the patient or compromise the patient’s ability to complete the study, at the discretion of the investigator.
[18] Second primary malignancy that is clinically detectable at the time of consideration for study enrollment (with the exception of in situ carcinoma of the cervix, adequately treated basal cell carcinoma, and early stage prostate cancer with Gleason grade ?6).
[19] Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin dose ?1.3 grams per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
[20] Brain metastases. Patients who are symptomatic for brain metastases must have a pretreatment computed tomography or magnetic resonance imaging (CT or MRI) of the brain. A patient with documented brain metastases at the time of study entry will be excluded from entering the study. Patients with prior brain metastases may be considered if they have completed their treatment for brain metastases, no longer require corticosteroids, and are asymptomatic.
[21] Significant weight loss (that is, ?10% of body weight) over the 6 weeks before study entry.
[22] Inability or unwillingness to take folic acid, vitamin B12 supplementation, or a corticosteroid.
[23] Have previously completed or withdrawn from this study or any other study investigating pemetrexed or have received any prior treatment with pemetrexed.
[24] Have been exposed to yellow fever vaccine, and live attenuated vaccines.
[25] Are taking oral anticoagulants.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

either (1) relapsed, advanced (Stage III or IV) NSCLC or (2) malignant pleural or peritoneal mesothelioma
MedDRA version: 8.1 Level: LLT Classification code 10029522 Term: Non-small cell lung cancer stage IV
MedDRA version: 9.1 Level: LLT Classification code 10059518 Term: Pleural mesothelioma malignant
MedDRA version: 9.1 Level: LLT Classification code 10056558 Term: Peritoneal mesothelioma malignant

Intervention(s)

Trade Name: Alimta
Product Name: ALIMTA
Product Code: LY231514
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: pemetrexed
CAS Number: 150399-23-8
Current Sponsor code: LY231514 disodium
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Main Objective: The primary objective of this Phase 2 study is to evaluate the safety of pemetrexed in patients with third-space fluid (pleural effusions or ascites).

Primary end point(s): The primary objective of this Phase 2 study is to evaluate the safety of pemetrexed in patients with third-space fluid (pleural effusions or ascites).

Safety will be assessed through clinical adverse events and CTCAE laboratory and nonlaboratory toxicities. The CTCAE scale will be used. (version 3.0, NCI 2006). A CTCAE rating will be performed before each cycle for any adverse events experienced during previous cycle.

Additionally, incidence of each of the following safety-related outcomes will be summarized:
• extent of exposure to study drug treatment
• number of blood transfusions required
• discontinuations due to adverse events or death
• deaths on study-drug treatment or within 30 days after last dose
• adverse events on study-drug treatment or within 30 days after last dose
• treatment-emergent adverse events.

The Lilly clinical research physician will review SAEs within the time frames mandated by company procedures and will review trends, laboratory analytes, and adverse events at periodic intervals."

Secondary Objective: The secondary objectives of the study are:
• to identify the adverse event profile of pemetrexed in patients with third-space fluid according to the Common Terminology Criteria for Adverse Events (CTCAE; version 3.0 [NCI 2006])
• to evaluate the pharmacokinetics of pemetrexed in patients with third-space fluid
• to assess the clinical relevance of any alterations in pemetrexed pharmacokinetics in patients with third-space fluid
• to provide pemetrexed dosing recommendations for patients with third-space fluid.

Secondary ID(s)

H3E-MC-JMHX(c)

2005-005535-10-ES