A Study for Patients With Recurrent or Metastatic Squamous Cell Head and Neck Cancer

Study Overview
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Brief Summary
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The purpose of this trial is to estimate progression free survival in patients with recurrent or metastatic head and neck cancer that have not received chemotherapy in this setting.

Detailed Description
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A 12 patient safety lead will evaluate side effects in patients receiving at least 2 cycles of the combination pemetrexed, cisplatin and cetuximab.

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

Conditions
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Head and Neck Neoplasms

Intervention / Treatment
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* Drug: Pemetrexed
* Drug: Cetuximab
* Drug: Cisplatin
* Dietary Supplement: Folic Acid
* Dietary Supplement: Vitamin B12


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of squamous cell carcinoma of head and neck (SCCHN) Recurrent or metastatic SCCHN, not amenable to local therapy At least 6 months since completion of systemic therapy (chemotherapy or biological anticancer therapy) No more than 1 prior systemic therapy, given as part of multimodal treatment for locally advanced disease; No prior systemic therapy for metastatic disease 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. Surgery (excluding prior diagnostic biopsy) must be completed at least 4 weeks before study enrollment. An estimated life expectancy of at least 12 weeks. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Oken et al. 1982). Biological tissue available for biomarker analysis on tumor tissue. Disease status may be measurable or nonmeasurable as defined by Response Evaluation Criteria in Solid Tumors Patient compliance and geographic proximity that allow for adequate follow-up. Adequate organ function Willingness to comply with Contraceptive Regimen 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. Exclusion Criteria: Nasopharyngeal, paranasal sinus, lip, or salivary gland cancer. Previously received treatment with monoclonal antibody therapy, or other signal transduction inhibitors of Epidermal Growth Factor Receptor therapy. Are receiving concurrent chronic systemic immune therapy, or chemotherapy for a disease other than cancer. 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. Have serious cardiac disease, such as symptomatic , unstable angina, or the history of myocardial infarction in the previous 12 months. Second primary malignancy that is clinically detectable at the time of consideration for study enrollment. Have had another primary malignancy other than Head and Neck cancer, 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 less than or equal to 6) localized prostate cancer will be eligible even if diagnosed and treated less than 2 years previously. 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. Have peripheral neuropathy 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. Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin dose less than or equal to 1.3 grams per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam). Unable or unwilling to take folic acid, vitamin B12, or prophylactic corticosteroids. Recent (within 30 days before enrollment) or concurrent yellow fever vaccination. Pregnant or breast-feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemetrexed + Cisplatin + Cetuximab<br>Participants will receive pemetrexed,cisplatin and cetuximab for up to 6 cycles (21 days per cycle) followed by optional maintenance of pemetrexed and cetuximab until disease progression. Optional maintenance therapy is permitted after at least 4 cycles of triplet combination therapy have been given. Cetuximab will be administered as an initial dose of 400 milligram per meter squared (mg/m^2) intravenous (IV) infusion and as a 250 mg/m^2 IV weekly dose thereafter. As Standard of care dietary supplements included: 350 to 1000 micrograms (µg) oral Folic Acid 5 times a day for the 7 days preceding the first dose of first dose of pemetrexed and continuing throughout treatment and for 21 days after the last dose of pemetrexed and 1000 µg vitamin B12 intramuscular injection (IM) during the week preceding the first dose of pemetrexed and every 9 weeks thereafter. | Drug: Pemetrexed<br>* Triplet Combination Therapy: 500 mg/m^2 administered intravenously on Day 1 of 21 day cycle for up to 6 cycles Maintenance Therapy: 500mg/m^2 administered intravenously on Day 1 of 21 day cycle until disease progression or unacceptable toxicity<br>* Other names: LY231514;Drug: Cetuximab<br>* Triplet Combination Therapy: 400 mg/m^2 administered intravenously on Day 1 of 21 day cycle for 1 cycle; 250 mg/m^2 administered IV infusion on Day 1 of 21 day cycle and then weekly for up to 6 cycles. Maintenance Therapy: 250 mg/m^2 administered intravenously on Day 1 of 21 day cycle and then weekly until disease progression or unacceptable toxicity<br>Drug: Cisplatin<br>* Triplet Combination Therapy: 75mg/m^2 administered intravenously on Day 1 of 21 day cycle for up to 6 cycles.<br>Dietary Supplement: Folic Acid<br>* Standard of care dietary supplements: 350 to 1000 µg orally 5 times a day for the 7 days preceding the first dose of first dose of pemetrexed and continuing throughout treatment and for 21 days after the last dose of pemetrexed.<br>Dietary Supplement: Vitamin B12<br>* Standard of care dietary supplements: 1000 µg IM during the week preceding the first dose of pemetrexed and every 9 weeks thereafter.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS based on Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines defined as the time from the date of first dose of study drug to first documented objective progressive disease (PD) or death from any cause. PD is defined as at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Baseline to date of PD or death up to 18.7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS defined as the time from the date of first dose of study drug to the date to death from any cause. | Baseline to date of death up to 18.7 months | 
| Percent of Participants With a Partial Response (PR) or a Complete Response (CR) | CR and PR based on RECIST Guidelines: CR is defined as the disappearance of all tumor lesions; PR is defined as at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LDs or the complete disappearance of target lesions, with persistence (but not worsening) of one or more nontarget lesions and the appearance of no new lesions. PD is defined as at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Date of first response to PD (up to 18.7 months) | 
| Change From Baseline in Participant Reported European-Quality of Life 5 Dimension Instrument (EQ-5D) Visual Analog Scale (VAS) at End of Triplet Combination Therapy and End of Maintenance Therapy | Vertical VAS - a 20 millimeter (mm), fractionated scale in the form of a thermometer with endpoints of 0 (worst imaginable health state) and 100 (best imaginable health state). Participants used the EQ-5D VAS scale to rate their overall health on the day the questionnaire was administered. Possible change values range from -100 (best imaginable health at baseline changed to worst possible health at visit) to 100 (worst possible health at baseline changed to best possible health at visit). | Baseline, End of Triplet Combination Therapy (up to Cycle 6 [4.2 months]), End of Maintenance Therapy (up to 18.7 months) | 
| Change From Baseline in Participant Reported EQ-5D Utility Score at End of Triplet Combination Therapy and End of Maintenance Therapy | EQ-5D Index is derived by converting the Descriptive System (participant is required to rate health by checking 1 [no limitation], 2 [some limitation] or 3 [severe or complete limitation] in 5 dimensions [mobility, self-care, usual activities, pain/comfort and anxiety/depression]) to a single summary index. A utility value assigned to each individual's health state based on the absence or presence of moderate or severe problems in the 5 dimensions. A regression equation defines a utility value for these health states. The possible values for health utility ranged from -0.59 (severe problems in all 5 dimensions) to 1 (no problem in all dimensions) on a scale where 0 represents death and 1 represents the best possible health state. Possible change values range from -1.59 (no problems at baseline to severe problems at visit) to 1.59 (severe problems at baseline to no problems at visit). | Baseline, End of Triplet Combination Therapy (up to 6 cycles [4.2 months]) , End of Maintenance Therapy (up to 18.7 months) | 
| Change From Baseline in Performance Status Scale for Head and Neck Cancer Patients (PSS-HNC) | PSS-HNC is a clinician-rated instrument designed to measure speaking and eating disabilities of participants with head and neck cancer and consists of 3 subscales: Normalcy of Diet (NOD) subscale measures the ability of the participants to eat a normal diet, scale ranged from 0 (non-oral feeding) to 100 (unrestricted diet); Understandability of Speech (UOS)subscale measured the degree a clinician was able to understand the participant's speech, subscale ranged from 0 (never understandable) to 100 (always understandable); Eating in Public (EIP) subscale, rating based on clinician question to the participant to report who he/she eats with and in what setting, subscale ranged from 0 (always eats alone) to 100 (no restriction of place, food, or companion). Change from baseline: negative value represents a decrease in function and a positive value represents an increase in function. | Baseline, Triplet Combination Therapy Cycles 2, 4, 6 (cycle = 21 days) and optional Maintenance Therapy Cycles 1, 3, 5 and 7 (cycle = 21 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharynx, Larynx, Cervical esophagus, Nose, Thyroid Gland, Parathyroid Gland