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

This study has been completed.
Information provided by (Responsible Party):
Eli Lilly and Company Identifier:
First received: March 15, 2010
Last updated: April 18, 2014
Last verified: April 2014
The purpose of this study is to look for an improvement in progression free survival with the combination of pemetrexed, carboplatin (or cisplatin) and cetuximab in participants with recurrent or metastatic squamous cell carcinoma of the head and neck.

Condition Intervention Phase
Head and Neck Neoplasms
Drug: Pemetrexed
Drug: Cetuximab
Drug: Carboplatin
Drug: Cisplatin
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of Pemetrexed in Combination With Carboplatin or Cisplatin and Cetuximab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Resource links provided by NLM:

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: From enrollment to measured progressive disease up to 15.3 months (tumor assessments performed every other cycle during study treatment, and then every 6 weeks during follow-up) ]
    PFS was defined as the duration from the date of enrollment to the first date of documented objective progressive disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. For participants who were not known to have died or to have had objective PD at the time of the data inclusion cutoff, PFS was censored at their last objective progression-free disease assessment prior to the cutoff date or the date of initiation of subsequent systemic anticancer therapy.

Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: From enrollment to the date of death from any cause up to 26.4 months (assessment completed during trial period at least every 3 months) ]
    OS is defined as the duration from the date of enrollment to the date of death from any cause. For participants who were alive at the time of the data inclusion cutoff, OS was censored at the date of last contact prior to that cut-off date.

  • Percentage of Participants Having a Confirmed Partial Response (PR) or Complete Response (CR) [ Time Frame: From enrollment to objectively determined progressive disease up to 15.3 months (tumor assessments performed every other cycle during study treatment until progressive disease) ]
    PR or CR is classified by the investigators according to RECIST criteria version 1.0. PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions; CR is the disappearance of all target and non-target lesions. Percentage of participants having a PR or CR is calculated as a total number of participants with PR or CR from enrollment until disease progression or recurrence divided by the total number of participants treated, then multiplied by 100.

  • Change From Baseline in Participant-Reported European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) [ Time Frame: Baseline, Day 1 of Cycles 2, 4, 6, cetuximab monotherapy Cycles 2 and 4 (21-day cycle) ]
    EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems/some or moderate problems/extreme problems) within a particular EQ-5D dimension. A regression equation defines a utility value for these health states to generate an index score. The possible values for index score range from -0.594 (severe problems in all 5 dimensions) to 1 (no problem in all dimensions) on a scale where 1 represents the best possible health state. The EQ-5D Visual Analog Scale (VAS) is used to record a participant's rating for his/her current health-related quality of life state on the day of questionnaire administration and is captured on a scale of 0 (worst imaginable health state) to 100 (best imaginable health state).

  • Change From Baseline in Performance Status Scale for Head and Neck Cancer (PSS-HNC) [ Time Frame: Baseline, Day 1 of Cycles 2, 4, 6, cetuximab monotherapy Cycles 2 and 4 (21-day cycle) ]
    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, subscale ranges from 0 (non-oral feeding) to 100 (unrestricted diet); understandability of speech (UOS) subscale measures the degree a clinician is able to understand the participant's speech, subscale ranges from 0 (never understandable) to 100 (always understandable); eating in public (EIP) subscale, rating based on the participant's response to the questions of whom he/she eats with and in what setting, subscale ranges 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.

Other Outcome Measures:
  • Number of Participants Who Died While on Treatment and Died During 30-Day Post-Treatment Discontinuation Follow-Up (FU) [ Time Frame: From enrollment to 30 days post-treatment discontinuation up to 26.4 months ]
    Presented are the number of participants who died due to adverse events (AEs) while on treatment and participants who died due to progressive disease (PD) during the 30-day post-treatment discontinuation FU.

Enrollment: 69
Study Start Date: August 2010
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Triplet Combination Therapy

Cycle 1:

Week 1 - Cetuximab 400 milligrams/square meter (mg/m²) on Day 1; Pemetrexed 500 mg/m² on Day 1; Carboplatin area under curve (AUC) 5 on Day 1 or Cisplatin 75 mg/m² on Day 1

Week 2 - Cetuximab 250 mg/m² on Day 1

Week 3 - Cetuximab 250 mg/m² on Day 1

Cycle 2-6:

Week 1 - Cetuximab 250 mg/m² on Day 1; Pemetrexed 500 mg/m² on Day 1; Carboplatin AUC 5 on Day 1 or Cisplatin 75 mg/m² on Day 1

Week 2 - Cetuximab 250 mg/m² on Day 1

Week 3 - Cetuximab 250 mg/m² on Day 1

Following Cycle 6, Cetuximab Monotherapy: 250 mg/m² intravenously weekly on Day 1

Drug: Pemetrexed
Administered intravenously, for maximum of 6 cycles.
Other Names:
  • Alimta
  • LY231514
Drug: Cetuximab

Administered intravenously in combination therapy, for a maximum of 6 cycles.

After the completion of 6 cycles, participants who have not experienced disease progression will continue on cetuximab monotherapy until disease progression.

Other Name: Erbitux
Drug: Carboplatin
Administered intravenously, for a maximum of 6 cycles
Drug: Cisplatin
Administered intravenously, for a maximum of 6 cycles


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologic or cytologic diagnosis of squamous cell head and neck cancer (HNC)

    • Recurrent disease (locally advanced or metastatic) that is not amenable to local therapy, (i) with at least 6 months since completion of systemic therapy (chemotherapy or biological anticancer therapy), and (ii) with no more than 1 prior multimodal therapy (such as concurrent chemoradiation with or without sequential chemotherapy) for locally advanced HNC tumor, and (iii) with no prior systemic therapy (chemotherapy or biological anticancer therapy) for metastatic disease; OR
    • Newly diagnosed distant metastatic disease (Stage IVc)
  • Prior therapies:

    • Radiation therapy must be completed at least 4 weeks before study enrollment. For palliative therapy, prior radiation therapy allowed <25% of the bone marrow and prior radiation to the whole pelvis is not allowed. Participants must have recovered from the acute toxic effects of the treatment prior to study enrollment.
    • Surgery (excluding prior diagnostic biopsy) must be completed at least 4 weeks before study enrollment. Participants must have fully recovered from any acute effects of surgery prior to study enrollment.
  • An estimated life expectancy of at least 12 weeks.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • Biological tissue available for biomarker analysis on tumor tissue.
  • Disease status must be measurable as defined by Response Evaluation Criteria in Solid Tumors (RECIST). 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.
  • Participant compliance and geographic proximity that allow for adequate follow-up.
  • Adequate organ function as defined by the following:

    • Bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) greater than or equal to 1.5 × 10⁹/liter (L), platelets greater than or equal to 100 × 10⁹/L, and hemoglobin greater than or equal to 9 grams/deciliter (g/dL).
    • Hepatic: bilirubin less than or equal to 1.5 × the upper limit of normal (ULN); alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) less than or equal to 3.0 × ULN (ALP, AST, and ALT less than or equal to 5.0 × ULN is acceptable if the liver has tumor involvement).
    • Renal: calculated creatinine clearance (CrCl) greater than or equal to 45 milliliters/minute (mL/min).
  • For women: Must be surgically sterile, postmenopausal, or compliant with a medically approved contraceptive regimen 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:

  • 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.
  • Are receiving concurrent chronic systemic immune therapy, or chemotherapy for a disease other than cancer.
  • Concurrent administration of any other antitumor therapy.
  • Known prior allergic/hypersensitivity reaction to any of the components of the study treatment.
  • Serious concomitant systemic disorder (for example, active infection) or psychiatric disorder that, in the opinion of the investigator, would compromise the participant's ability to complete the study.
  • Have serious cardiac disease, such as symptomatic angina, 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 HNC, unless that prior malignancy was treated at least 2 years previously with no evidence of recurrence. Exception: Participants 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.
  • Nasopharyngeal, paranasal sinus, lip, or salivary gland cancer.
  • 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 of Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or higher.
  • Have central nervous system (CNS) metastases (unless the participant 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 participants to rule out brain metastases, but is not required in asymptomatic participants.
  • 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.
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Please refer to this study by its identifier: NCT01087970

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Sponsors and Collaborators
Eli Lilly and Company
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

Responsible Party: Eli Lilly and Company Identifier: NCT01087970     History of Changes
Other Study ID Numbers: 13491
H3E-MC-S132 ( Other Identifier: Eli Lilly and Company )
Study First Received: March 15, 2010
Results First Received: April 18, 2014
Last Updated: April 18, 2014

Keywords provided by Eli Lilly and Company:

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors processed this record on May 24, 2017