A Randomized Phase 3 Study of Pemetrexed in Combination with Cisplatin Versus Cisplatin Monotherapy in Patients with Recurrent or Metastatic Head and Neck Cancer - NA

• Register: EUCTR
• Last refreshed on: 24 April 2012
• Main ID: EUCTR2006-003158-12-HU
• Date of registration: 25/08/2006
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company limited
• Public title: A Randomized Phase 3 Study of Pemetrexed in Combination with Cisplatin Versus Cisplatin Monotherapy in Patients with Recurrent or Metastatic Head and Neck Cancer - NA
• Scientific title: A Randomized Phase 3 Study of Pemetrexed in Combination with Cisplatin Versus Cisplatin Monotherapy in Patients with Recurrent or Metastatic Head and Neck Cancer - NA
• Date of first enrolment: 16/10/2006
• Target sample size: 790
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-003158-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

France, Germany, Hungary, Italy, Netherlands, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
[1] Histologic or cytologic diagnosis of squamous cell HNC, either:
• recurrent disease (locally advanced or metastatic) that is not amenable to local therapy, (i) with at least 6 months since completion of surgery, radiation, and/or systemic therapy (chemotherapy or biological anticancer therapy), and (ii) with no more than 1 prior radiation regimen for primary HNC tumor, and (iii) with no prior systemic therapy (chemotherapy or biological anticancer therapy) for metastatic disease; OR
• newly diagnosed distant metastatic disease.
[2] Prior radiation therapy allowed to <25% of the bone marrow (Cristy and Eckerman 1987). Prior radiation to the whole pelvis is not allowed. Prior radiotherapy for palliative treatment must be completed at least 4 weeks before study enrollment. Patients must have recovered from the acute toxic effects of the treatment prior to study enrollment.
[3] Life expectancy of at least 3 months.
[4] Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 (Oken et al. 1982). See Protocol Attachment JMHR.3.
[5] Disease status may be measurable or nonmeasurable as defined by Response Evaluation Criteria in Solid Tumors (RECIST; Therasse et al. 2000). Positron emission tomography (PET) scans and ultrasounds may not be used for lesion measurements.
[6] Patient compliance and geographic proximity that allow for adequate follow-up.
[7] Adequate organ function as defined by the following:
• Bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) =1.5 x 10e9/L, platelets =100 x 10e9/L, and hemoglobin =9 g/dL.
• Hepatic: bilirubin < or = 1.5 x the upper limit of normal (ULN); alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) >3.0 x ULN. (ALP, AST, and ALT >5.0 x ULN is acceptable if the liver has tumor involvement.)
• Renal: calculated creatinine clearance (CrCl) =60 mL/min based on the standard Cockcroft and Gault formula (Cockcroft and Gault 1976). (See Protocol Attachment JMHR.4.)
[8] Signed informed consent from patient.
[9] Patients at least 18 years of age.
[10] For women: Must be surgically sterile, postmenopausal, or compliant with a medically approved contraceptive regimen (for example, intrauterine device [IUD], birth control pills, or barrier device) during and for 6 months after the treatment period; must have a negative serum or urine pregnancy test within 7 days before study enrollment, and must not be breast-feeding.
For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 6 months after the treatment period.

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:
[11] Prior systemic therapy (chemotherapy or biological anticancer therapy) for metastatic disease.
[12] 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.
[13] Serious concomitant systemic disorder (for example active infection or cardiac disease) or psychiatric disorder that, in the opinion of the investigator, would compromise the patient’s ability to complete the study.
[14] Presence of clinically significant (by physical exam) third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry.
[15] Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
[16] Have had another primary malignancy other than HNC, unless that prior malignancy was treated at least 2 years previously with no evidence of recurrence. Exception: Patients with a history of in situ carcinoma of the cervix, nonmelanoma skin cancer, or low-grade (Gleason score =6) localized prostate cancer will be eligible even if diagnosed and treated less than 2 years previously.
[17] Nasopharyngeal, paranasal sinus, lip, or salivary gland cancer.
[18] Have central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy). Brain imaging is required in symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients.
[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] Unable or unwilling to take folic acid, vitamin B12, or prophylactic corticosteroids.
[21] Concurrent administration of any other antitumor therapy.
[22] Pregnant or breast-feeding.



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

Health Condition(s) or Problem(s) studied

Recurrent or Metastatic Head and Neck Cancer
MedDRA version: 8.1 Level: LLT Classification code 10060121 Term: Squamous cell carcinoma of head and neck

Intervention(s)

Trade Name: Alimta
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Pemetrexed
CAS Number: 150399-23-8
Current Sponsor code: LY231514
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): The primary outcome measure for this trial is Overall Survivaln (OS). All randomized patients will be included in the analysis of OS. The primary analysis will be the comparison of OS between the 2 study treatments using a stratified log-rank test at two-sided a=0.05 with the following prognostic variables as stratification factors: performance status (0 or 1 versus 2), previously treated for HNC (no versus yes), distant metastasis (no versus yes), and prior platinum-based therapy (no versus yes). Kaplan-Meier (K-M) estimation (Kaplan and Meier 1958) including generating K-M curve, quartiles, and interval estimation using 95% confidence intervals will also be done. The supportive analysis of the primary outcome will be performed to obtain treatment effect after adjusting for the prognostic variables using Cox regression model (Cox 1972).

Secondary Objective: The secondary objectives of this study are to compare between the 2 treatment arms:
• progression-free survival (PFS)
• overall response rate (ORR)
• duration of response (DoR) for responding patients
• time to worsening (TTW) in dimensions of health-related quality of life (HRQoL)
• change from baseline in dimensions of HRQoL using FACT-H&N
• the safety and adverse event profile

Main Objective: The primary objective of this study is to compare the OS of pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 every 3 weeks to the OS of single-agent cisplatin 75 mg/m2 every 3 weeks in patients with HNC that is recurrent and not amenable to local therapy (surgery or radiation) or newly diagnosed distant metastatic disease.

Secondary ID(s)

H3E-MC-JMHR

2006-003158-12-NL