| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Carcinoma de células escamosas de cabeza y cuello recurrente o metastásico |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10063569 |
| E.1.2 | Term | Metastatic squamous cell carcinoma |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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. |
|
| E.2.2 | Secondary objectives of the trial |
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. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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. 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 must be measurable as defined by Response Evaluation Criteria in Solid Tumors (Therasse et al. 2000). The index lesion must not be in a prior irradiated area. 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. |
|
| E.4 | Principal 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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression Free Survival |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Information not present in EudraCT |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 13 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Last visit of the last subject. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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