Phase 2 Study of Pemetrexed in Combination with Cisplatin and Cetuximab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

• Register: EUCTR
• Last refreshed on: 3 June 2013
• Main ID: EUCTR2009-011611-21-DE
• Date of registration: 28/08/2009
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company Ltd.
• Public title: Phase 2 Study of Pemetrexed in Combination with Cisplatin and Cetuximab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
• Scientific title: Phase 2 Study of Pemetrexed in Combination with Cisplatin and Cetuximab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
• Date of first enrolment: 02/12/2009
• Target sample size: 65
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-011611-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Belgium, Germany, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
[1] Histologically confirmed diagnosis of squamous cell carcinoma of head and neck (SCCHN)

o Recurrent or metastatic SCCHN, not amenable to local therapy

o At least 6 months since completion of systemic therapy (chemotherapy or biological anticancer therapy)

o No more than 1 prior systemic therapy, given as part of multimodal treatment for locally advanced disease; induction chemotherapy and subsequent concurrent chemoradiation are considered as 1 regimen

o No prior systemic therapy for metastatic disease

[2] Prior therapies:

o Radiation therapy must be completed at least 4 weeks before study enrollment (first dose of study therapy). For palliative therapy, prior radiation therapy allowed to <25% of the bone marrow (Cristy and Eckerman 1987), and prior radiation to the whole pelvis is not allowed. Patients must have recovered from the acute toxic effects of the treatment prior to study enrollment.

o Surgery (excluding prior diagnostic biopsy) must be completed at least 4 weeks before study enrollment. Patients must have fully recovered from any acute effects of surgery prior to study enrollment.

[3] An estimated life expectancy of at least 12 weeks.

[4] Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Oken et al. 1982).

[5] Biological tissue available for biomarker analysis on tumor tissue.

[6] Disease status may be measurable or nonmeasurable as defined by Response Evaluation Criteria in Solid Tumors (RECIST; Therasse et al. 2000; Protocol Attachment S123.4). Positron emission tomography (PET) scans and ultrasounds may not be used for lesion measurements.

[7] Patient compliance and geographic proximity that allow for adequate follow-up.

[8] Adequate organ function as defined by the following:

o Bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) = 1.5 billion per litre, platelets = 100 billion per litre, and hemoglobin = 9 g/dL.

o Hepatic: bilirubin = 1.5 × the upper limit of normal (ULN); alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) = 3.0 × ULN (ALP, AST, and ALT = 5.0 × ULN is acceptable if the liver has tumor involvement).

o Renal: calculated creatinine clearance (CrCl) = 60 mL/min. These tests must be performed within 7 days prior to Day 1 of Cycle 1.

[9] Signed informed consent from patient.

[10] Patients at least 18 years of age.

[11] 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:
[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] Previously received treatment with monoclonal antibody therapy, or other signal transduction inhibitors of EGFR-targeting therapy.

[14] Are receiving concurrent chronic systemic immune therapy, or chemotherapy for a disease other than cancer.

[15] Concurrent administration of any other antitumor therapy.

[16] Known prior allergic/hypersensitivity reaction to any of the components of the study treatment.

[17] Serious concomitant systemic disorder (for example, active infection) or psychiatric disorder that, in the opinion of the investigator, would compromise the patient’s ability to complete the study.

[18] Have serious cardiac disease, such as symptomatic angina [NYHA grade III and IV], unstable angina, or the history of myocardial infarction in the previous 12 months.

[19] Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.

[20] 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.

[21] Nasopharyngeal, paranasal sinus, lip, or salivary gland cancer.

[22] 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.

[23] Have peripheral neuropathy of Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or higher.

[24] 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.

[25] 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).

[26] Unable or unwilling to take folic acid, vitamin B12, or prophylactic corticosteroids.

[27] Recent (within 30 days before enrollment) or concurrent yellow fever vaccination.

[28] Pregnant or breast-feeding.


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

Health Condition(s) or Problem(s) studied

Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
MedDRA version: 14.1 Level: PT Classification code 10063569 Term: Metastatic squamous cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Trade Name: Alimta
Pharmaceutical Form: Powder for infusion
INN or Proposed INN: PEMETREXED DISODIUM
CAS Number: 150399-23-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Product Name: Cisplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CISPLATIN
CAS Number: 15663-27-1
Other descriptive name: (SP-4-2)-diamminedichloroplatinum
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Trade Name: Erbitux
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: CETUXIMAB
CAS Number: 205923-56-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Main Objective: The primary objective is to estimate the progression-free survival (PFS) for the combination of pemetrexed plus cisplatin plus cetuximab followed by optional pemetrexed plus cetuximab maintenance therapy.

Primary end point(s): Progression Free Survival

Secondary Objective: The secondary objectives of the study are:

• To estimate overall survival (OS).

• To estimate the overall objective response rates (ORR) according to the Response Evaluation Criteria in Solid Tumors (RECIST; Therasse et al. 2000).

• To examine the safety and toxicity profile of study treatment.

• To assess health status using patient-reported EQ-5D and physician-assessed head and neck cancer (HNC) symptoms.

• To assess biomarkers relevant to the safety, efficacy, and mechanism of action of pemetrexed, cetuximab, and cisplatin.

• To assess the association between biomarkers and clinical outcome.

Secondary ID(s)

H3E-MC-S123

2009-011611-21-BE